Discover Seattle Cancer Care Alliance’s groundbreaking research at ASCO20 Virtual Scientific Program, the most comprehensive oncology event of the year. 

From May 29 - May 31, the American Society of Clinical Oncology  (ASCO) will host its annual meeting, showcasing important scientific insights from around the world. While this year's meeting is virtual, more than 20 world-class physicians and researchers from Seattle Cancer Care Alliance (SCCA) and our partner organizations will be presenting their pioneering research. 

From a giant of cancer care to clinical trials that are instrumental in changing the way patients are treated, SCCA is a leader in turning scientific discovery into exciting new treatments.

Learn more about cancer care at SCCA

Highlighted Abstracts 
 
Our leading physician researchers will have their oral presentations, poster discussions and poster sessions available on demand through the virtual conference.
Clinical impact of COVID-19 on patients with cancer: Data from the COVID-19 and Cancer Consortium (CCC19).
Petros Grivas, MD, PhD
Clinical science symposium

There are limited data on COVID-19 in patients with cancer. We characterize the outcomes of patients with cancer and COVID-19 and identify potential prognostic factors.

End-of-life health care utilization (EOLHCU) in patients with recurrent, metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with immune checkpoint inhibitors (IO).
Jay Liao, MD
E-publication

Demographic and EOLHCU trends are undefined in the growing population of IO-treated RMHNSCC; we sought to study these in a single institution retrospective study.

Sarcomatoid urothelial carcinoma: Oncologic outcomes from a tertiary center and SEER-Medicare data.
Petros Grivas, MD, PhD
E-publication

Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive bladder cancer variant with little evidence regarding prognostic characteristics and response to neoadjuvant chemotherapy (NAC). In this study, we delineate oncologic outcomes in patients with SUC after radical cystectomy (RC), presenting data from our institutional database and SEER-Medicare.

Treatment patterns in pancreatic cancer: Differences between expert and community practitioners.
E. Gabriela Chiorean, MD
E-publication

Expanding systemic therapy options continue to improve outcomes for patients (pts) with pancreatic cancer (PCa) in both the unresectable and resectable disease settings. We developed an online treatment (Tx) decision support tool designed to provide community healthcare providers (HCPs) with case-specific recommendations from 5 PCa experts. Here, we report an analysis of cases entered into the tool by HCPs, comparing their planned Tx with expert recommendations and assessing the impact of those recommendations on intended HCP Tx decisions.

Phase I, first-in-human study of AbGn-107, a novel antibody-drug conjugate (ADC), in patients with gastric, colorectal, pancreatic or biliary cancers.
Andrew Coveler, MD
E-publication

AbGn-107 is an ADC directed against AG-7 antigen, a Lewis A-like glycol-epitope expressed in 24-61% of gastric (G), colorectal (CRC), pancreatic (PDA), and biliary (BIL) cancers. Based on promising antitumor activity of AbGn-107 in both in vitro and in vivo preclinical studies, we performed a Phase Ia trial in patients with the aforementioned GI malignancies.

Treatment of metastatic recurrence of urothelial carcinoma after previous cisplatin-based chemotherapy: A retrospective comparison of different chemotherapy regimens.
Evan Yu, MD
E-publication

The optimal choice of first-line chemotherapy for urothelial carcinoma (UC) patients who recur after previous cisplatin-based chemotherapy for locally-advanced disease is unclear. Our objective is to compare the efficacy of platinum (PBC) versus non-platinum (NPBC) based first-line chemotherapy regimens for such patients after metastatic recurrence.

Characterization of cytokine release syndrome (CRS) and neurological events (NEs) in the phase I TRANSCEND NHL 001 trial of lisocabtagene maraleucel (liso-cel) for patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL).
David G. Maloney, MD, PhD
E-publication

Clinical studies of liso-cel show low incidences of severe CRS and NEs. Pts with high tumor burden and inflammation are at higher risk of CRS and NEs (Borrega, Hemasphere 2019). Here, we characterize the presenting symptoms, timing, and management of CRS and NEs in pts with R/R LBCL treated with liso-cel in TRANSCEND NHL 001 (NCT02631044). A deeper understanding of CRS/NEs after liso-cel treatment may help clinicians identify and manage these toxicities.

Perioperative blood transfusion and postoperative outcomes in patients undergoing radical cystectomy for bladder cancer.
Petros Grivas, MD, PhD
E-publication

Perioperative blood transfusion (PBT) has been associated with worse outcomes in surgical oncology across tumor types. We report our institutional experience of postoperative outcomes related to PBT utilization, in patients (pts) with bladder cancer (BC) treated with radical cystectomy (RC). We hypothesized that PBT is associated with worse clinical outcomes.

Intravesical therapy and risk of cystectomy and bladder cancer death after BCG fails.
John L. Gore, MD
E-publication

Management of non-muscle-invasive bladder cancer (NMIBC) when BCG fails engages complex decision-making that incorporates consideration of radical cystectomy (RC) and several intravesical options. We sought to characterize trends in practice variation and health outcomes for patients receiving intravesical therapy and radical cystectomy for presumption of recurrent or progressive high-risk NMIBC that has failed BCG.

Associations between baseline body composition and cancer-specific mortality following neoadjuvant chemotherapy and radical cystectomy for bladder cancer.
Petros Grivas, MD, PhD
E-publication

Sarcopenia is a modifiable risk factor independently associated with cancer-specific mortality (CSM) in bladder cancer (BC). Sarcopenic obesity, where obesity is measured by fat mass index [FMI, total body fat (kg)/height(m)2], has been proposed as an additive insult. To date, studies have overwhelmingly been performed in patients treated without neoadjuvant chemotherapy (NAC). Herein, we evaluate associations between baseline skeletal muscle index (SMI), FMI, and CSM in patients treated with NAC and radical cystectomy (RC).

ER, PR, and HER2 expression in Ugandan breast cancer patients: An evaluation of in-country RT-PCR compared to IHC.
Julie Gralow, MD
E-publication

Breast cancer, the most common cancer in sub-Saharan Africa (SSA), is characterized by poor survival. An accurate assessment of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2) status, typically via immunohistochemistry (IHC), is considered essential to provide prognostic data and guide therapeutic decision-making. However, due to inaccessible IHC services, these data are often unavailable in many parts of SSA; alternate methods need to be explored. Given the lab infrastructure developed in response to the HIV pandemic, RT-PCR testing is more readily accessible and feasible in SSA. Here we assess the potential of RT-PCR in evaluating the receptor status of women with breast cancer in Uganda.

Small Cell Bladder Cancer: Treatment Patterns and Clinical Outcomes.
Petros Grivas, MD, PhD
E-publication

Small cell bladder cancer (SCBC) is a rare histologic variant associated with poor oncologic outcomes and propensity for metastasis, however, there remains a paucity of data regarding the role of chemoradiation. We review our institutional experience of patients with small cell bladder cancer (SCBC) treated with radical cystectomy (RC) versus concurrent chemoradiotherapy (CCRT).

Phase I results from a phase 1/2 multi-center study of nab-sirolimus combined with mFOLFOX6+bevacizumab (FB) as first-line (1L) therapy in patients (pts) with metastatic colorectal cancer (mCRC) with or without PTEN loss.
E. Gabriela Chiorean, MD
E-publication

The PI3K/mTOR pathway overactivation and loss of PTEN occur in 20-40% of mCRC pts. A recent phase 1/2 study in mCRC pts showed evidence that everolimus added to 1L SOC treatment improved outcomes, in particular in pts with PTEN loss (Gilcrease, 2019). This prospective, single-arm phase 1/2 study aims to identify the optimal dose and schedule of nab-sirolimus (ABI-009), an mTOR inhibitor, plus FB and evaluate the safety and preliminary efficacy of this regimen.

Skeletal muscle index and adverse events during a bladder cancer treatment episode.
Petros Grivas, MD, PhD
E-publication

While sarcopenia is associated with increased mortality in bladder cancer, there is limited data in patients treated with neoadjuvant chemotherapy (NAC) that associates skeletal muscle index (SMI) and adverse treatment-associated outcomes. Herein, we evaluate associations between baseline SMI and severe adverse events (SAEs) during NAC and post-radical cystectomy (RC) 90-day Clavien ≥3 complications

Patient-centered pathology reports for breast cancer care: Interim results of a randomized pilot study.
Sara Javid, MD
E-publication

Receiving a new cancer diagnosis event is a daunting event, quickly followed by complex decision-making between patients and care teams. In order for patients to fully engage in shared decision-making with their providers, they must have access to understandable, patient-centered information that empowers them to take an active role. Yet cancer pathology reports currently target providers and are marred by complex medical terminology. To address this gap, we designed and piloted patient-centered pathology reports (PCPRs) for breast cancer surgical pathology. We hypothesized that PCPRs would result in patients having greater pathology knowledge and decisional self-efficacy.

The impact of telemedicine on patient-reported outcomes in urologic oncology.
John L. Gore, MD
E-publication

Nearly 20% of Americans live in rural communities. These individuals face barriers to accessing cancer care, including prevalent poverty and substantial travel burden to seeing cancer providers. We aimed to assess the impact of a rurally focused telemedicine program on patient outcomes in our urologic oncology outpatient clinic.

Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416).
Julie Gralow, MD
Oral abstract session

PARP inhibitors(i) are effective in BRCA-mutation-associated metastatic breast cancer(MBC). However, there are no studies evaluating PARPi + platin chemotherapy in BRCA wild-type(wt) TNBC. Approximately 1/2 of BRCAwt TNBC demonstrate homologous recombination deficiency (HRD) resulting in a BRCA-like phenotype which might render them sensitive to PARPi. S1416 compared the efficacy of cisplatin plus PARPi veliparib (Vel) or placebo (P) in 3 groups of MBC: gBRCA+; BRCA-like; and non-BRCA-like.

SWOG S1505: Results of perioperative chemotherapy (peri-op CTx) with mfolfirinox versus gemcitabine/nab-paclitaxel (Gem/nabP) for resectable pancreatic ductal adenocarcinoma (PDA)
E. Gabriela Chiorean, MD
Oral abstract session

Clinical outcomes after curative treatment of resectable PDA remain suboptimal. To assess the potential of early control of systemic disease with multiagent peri-op CTx, we conducted a prospective trial in the National Clinical Trials Network.

FRACTION-RCC: Innovative, high-throughput assessment of nivolumab + ipilimumab for treatment-refractory advanced renal cell carcinoma (aRCC).
Scott S. Tykodi, MD, PhD
Oral abstract session

The immuno-oncology (I-O) combination nivolumab + ipilimumab (NIVO+IPI) is approved for first-line (1L) and NIVO is approved for second-line treatment post TKI therapy in aRCC. The open-label, randomized, phase 2 Fast Real-Time Assessment of Combination Therapies in Immuno-Oncology (FRACTION-RCC; NCT02996110) platform study has an adaptive design allowing rapid evaluation of I-O therapies, including NIVO+IPI or other investigational combinations. This FRACTION analysis reports preliminary outcomes with NIVO+IPI in aRCC pts after progression on checkpoint inhibitor therapy.

TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded).
Shaveta Vinayak, MD, MS
Oral abstract session

Olaparib, a PARP inhibitor, is approved for HER2-negative MBC in gBRCA1/2 mutation carriers. Olaparib Expanded, an investigator-initiated study, assessed the response to olaparib in MBC patients with sBRCA1/2 mutations or g/s mutations in DDR-pathway genes other than BRCA1/2.

Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (MPM)—A PrECOG LLC study.
Bernardo Goulart, MD
Oral abstract session

First-line CP was FDA-approved in 2004 for unresectable MPM. Given the role of inflammation in MPM and promising responses to PD-1 pathway blockade in pretreated MPM, we conducted a phase 2 single arm study of the anti-PD-L1 antibody, durvalumab (durva), combined with CP for patients (pts) with untreated MPM of any subtype.

IMvigor010: Primary analysis from a phase III randomized study of adjuvant atezolizumab (atezo) versus observation (obs) in high-risk muscle-invasive urothelial carcinoma (MIUC).
Petros Grivas, MD, PhD
Oral abstract session

Radical surgery ± cisplatin-based neoadjuvant chemo (NAC) is the mainstay treatment (tx) for MIUC, with no conclusive level 1 evidence for adjuvant chemo (AC). Here we present the primary analysis from IMvigor010, a global, open-label, multicenter, randomized trial of adjuvant atezo (anti–PD-L1; approved in metastatic UC [mUC] settings) in pts with MIUC at high risk of recurrence following primary resection.

Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC).
William Harris, MD
Oral abstract session

The combination of dual immune checkpoint inhibitors (ICI) T (anti–CTLA-4) and D (anti–PD-L1) showed tolerability with a promising objective response rate (ORR) in the initial cohort of this study (NCT02519348). Subsequent evaluation of pts with solid tumors treated with increasing doses of T suggested priming with a higher dose of T may induce a stronger immune response and enhance anti-tumor activity. Thus, the randomized expansion cohorts comprised 4 arms evaluating T and D as monotherapies and 2 T+D regimens, including a novel T+D regimen featuring a single, priming dose of T.

Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC).
Julie Gralow, MD
Oral abstract session

The standard of care for HER2-positive EBC is chemotherapy plus one year of HER2-directed therapy. However, recurrence—particularly in high-risk populations—remains a problem, as does systemic chemotherapy-associated toxicity. In KAITLIN, we aimed to improve efficacy and reduce toxicity by replacing taxanes and trastuzumab with T-DM1.

Interim analysis of ZUMA-5: A phase II study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory indolent non-Hodgkin lymphoma (R/R iNHL).
David G. Maloney, MD, PhD
Oral abstract session

Advanced stage iNHL, including follicular lymphoma (FL) and marginal zone lymphoma (MZL), is considered incurable as most pts experience multiple relapses (Wang, et al. Ther Adv Hematol. 2017), highlighting a need for novel therapies. Here, we present interim results from ZUMA-5, a Phase 2, multicenter study of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in pts with R/R iNHL.

Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis.
Petros Grivas, MD, PhD
Plenary session: May 31

Platinum-based chemotherapy is an active 1L regimen for advanced UC; however, progression-free survival (PFS) and overall survival (OS) are generally short because of chemotherapy resistance. This randomized, phase 3 trial (JAVELIN Bladder 100; NCT02603432) evaluated avelumab (anti–PD-L1) as maintenance therapy following response or stable disease with 1L platinum-based chemotherapy in patients with advanced UC.

Cumulative incidence of financial hardship in metastatic colorectal cancer patients: Primary endpoint results for SWOG S1417CD.
Veena Shankaran, MD
Poster discussion session

Despite evidence that rising cancer care costs are contributing to “financial toxicity” in cancer pts, no studies, to our knowledge, have prospectively assessed the financial impact of cancer diagnosis (dx) using both self-reported and objective financial measures. S1417CD, led by the SWOG Cancer Research Network and conducted in the NCI Community Oncology Research Program (NCORP), was the first national prospective cohort study to evaluate time-to-first evidence of major financial hardship (MFH) in pts with newly diagnosed mCRC. We present results of the primary endpoint analysis.

TRANSFORMER: Bipolar androgen therapy (BAT) versus enzalutamide (E) for castration-resistant metastatic prostate cancer (mCRPC).
Michael Schweizer, MD
Poster discussion session

Rapid cycling between high and low testosterone (T) (i.e BAT) produces tumor response in mCRPC, and may overcome resistance to newer AR therapies. Here we report a randomized study comparing BAT to E in men with mCRPC progressing on abiraterone (A).

 

CodeBreak 100: Activity of AMG 510, a novel small molecule inhibitor of KRASG12C, in patients with advanced colorectal cancer.
Andrew Coveler, MD
Poster discussion session

Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation is associated with poor prognosis in colorectal cancer (CRC). AMG 510 is a first-in-class small molecule that specifically and irreversibly inhibits KRASG12C by locking it in the inactive guanosine diphosphate-bound state. In a previous interim analysis of the phase 1, first-in-human trial of AMG 510, we observed a favorable safety profile and preliminary antitumor activity in patients (pts) with advanced solid tumors harboring KRAS p.G12C. Here, we present updated data in pts with CRC.

A phase II study of oraxol in the treatment of unresectable cutaneous angiosarcoma.
Michael Wagner, MD
Poster discussion session

Oraxol is a combination of oral paclitaxel and a novel oral P-glycoprotein inhibitor, HM30181A. Cutaneous angiosarcomas are highly aggressive malignant tumors with poor prognosis. Currently there is no FDA-approved treatment.

Risk of cardiovascular disease in women with and without a history of breast cancer: The Pathways Heart Study.
Heather Greenlee, ND, PhD
Poster discussion session

Breast cancer (BC) survivors are at increased risk of cardiovascular disease (CVD) following diagnosis, as compared to women without BC. To provide a population-based estimate of CVD risk in BC survivors, we compared risk of CVD events in women with and without BC history enrolled in the Kaiser Permanente Northern California (KPNC) integrated health system.

Predictive model of aromatase inhibitor non-adherence using patient-reported outcomes in women with breast cancer (SWOG S1105).
Julie Gralow, MD
Poster discussion session

Non-adherence to aromatase inhibitors (AIs) for breast cancer is common and increases risk of recurrence. Few prospective studies have systematically evaluated factors associated with non-adherence. We analyzed baseline sociodemographic, prescription, and patient reported outcome (PRO) symptoms and quality-of-life to identify factors associated with non-adherence prospectively over 3-years.

Association of gene expression with clinical outcomes in patients with renal cell carcinoma treated with pembrolizumab in KEYNOTE-427.
Scott S. Tykodi, MD, PhD
Poster discussion session

We assessed the association of baseline RNA-sequencing–based gene expression signatures and DNA alterations with response or resistance to pembrolizumab in patients with advanced renal cell carcinoma in cohorts A (clear cell; n = 110) and B (non-clear cell; n = 165) of the phase 2 KEYNOTE-427 study (NCT02853344).

Gender differences in faculty rank and subspecialty choice in academic medical oncology.
Nancy E. Davidson, MD
Poster discussion session

The gender gap in the United States healthcare field has been closing. In 2000 women made up 45% of medical school matriculants and by 2017 outnumbered men. Based on our personal observations at academic meetings, however, we hypothesized that gender differences persist in faculty rank and subspecialty choice in academic medical oncology.

Prospective study of an AI enabled online intervention to increase delivery of guideline compliant cancer care, on the ground.
Benjamin O. Anderson, MD
Poster discussion session

Despite survival benefits of guideline compliant cancer care, under treatment and over treatment are prevalent. Navya is an AI enabled online intervention that matches a patient’s medical record with NCCN and NCG guidelines (National Cancer Grid, India) and layers live multidisciplinary expert review to recommend actionable treatment plans. It was developed to standardize care and mitigate morbidity and mortality, by delivering on-t ime, guideline based expert treatment plans.

SGNLVA-001: A phase I open-label dose escalation and expansion study of SGN-LIV1A administered weekly in breast cancer.
Jennifer M. Specht, MD
Poster session

LIV-1 is a highly prevalent transmembrane protein in breast cancer cells. Ladiratuzumab vedotin (LV), SGN-LIV1A, is an investigational antibody-drug conjugate (ADC) that targets LIV-1 via a humanized IgG1 monoclonal antibody conjugated to monomethyl auristatin E (MMAE) by a protease-cleavable linker. LV is internalized when it binds LIV-1 on cell surfaces and MMAE is released, which binds tubulin and induces apoptosis. LV has been shown to be active and tolerable in metastatic breast cancer (mBC) at a recommended dose of 2.5 mg/kg every 21 days (Modi 2017). More frequent, fractionated dosing has improved the activity and/or safety of other ADCs. Thus, this study is actively accruing subjects with metastatic triple negative breast cancer (mTNBC; estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) receptor-negative) and endocrine-resistant ER+ or PR+ (hormone receptor [HR+])/HER2-negative mBC to test weekly dosing of LV (Days 1, 8, and 15 of every 3-week cycle).

Pembrolizumab (pembro) for the treatment of patients with Bacillus Calmette-Guérin (BCG) unresponsive, high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Over two years follow-up of KEYNOTE-057.
Petros Grivas, MD
Poster session

Pembro was recently approved for the treatment of HR NMIBC based on results from the phase 2 KEYNOTE-057 (NCT02625961) study. Herein we present safety, efficacy, and posttreatment outcomes with > 2 y follow-up from KEYNOTE-057 cohort A.

Phase I/II study of SAR439859, an oral selective estrogen receptor degrader (SERD), in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC).
Hannah M. Linden, MD
Poster session

SERDs competitively antagonize and degrade the ER and can block signaling in ER-dependent tumors resistant to standard endocrine therapy (ET). This study (NCT03284957) investigates SAR439859, a potent oral SERD, in ER+/HER2- mBC. We present pooled dose escalation/expansion (Part A/B) data for SAR439859.

Clinically advanced renal cell carcinoma (RCC) and renal sarcoma (RSC) in young patients: A comprehensive genomic profiling (CGP) study.
Petros Grivas, MD, PhD
Poster session

We queried whether the landscape of genomic alterations (GA) would differ in patients with metastatic RCC under 40 years of age (under40) and patients 40 years of age or older (over40).

Outpatient treatment with lisocabtagene maraleucel (liso-cel) across a variety of clinical sites from three ongoing clinical studies in relapsed/refractory (R/R) large B-cell lymphoma (LBCL).
David G. Maloney, MD, PhD
Poster session

Currently approved CAR T cell therapies are generally administered as inpatient (inpt) treatment at university medical centers due to concerns about frequency, onset, severity, and management of AEs, including cytokine release syndrome (CRS) and neurologic events (NEs). We sought to characterize whether patients (pts) could be safely monitored in the outpatient (outpt) setting after receiving liso-cel, an investigational, CD19-directed CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells, across university and non-university sites in TRANSCEND NHL 001 (NCT02631044), OUTREACH (NCT03744676), and PILOT (NCT03483103).

Phase II study: Efficacy and safety of PSMA-targeted radioligand therapy
Evan Yu, MD
Poster session

PSMA is a transmembrane glycoprotein expressed in normal human prostate epithelium at low levels, but highly upregulated in metastatic prostate cancer (PC). 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown highly promising diagnostic performance for detection of metastatic disease, with potential to identify disease amenable to theranostic targeting. 

DAROL: DARolutamide ObservationaL study patients in nonmetastatic castration-resistant prostate cancer (nmCRPC) patients.
Evan Yu, MD
Poster session

Patients (pts) with prostate cancer treated with prolonged androgen deprivation therapy (ADT) will eventually develop castration-resistant disease. 

Phase I study of AMG 509, a STEAP1 x CD3 T cell-recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).
Evan Yu, MD
Poster session

Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a cell surface antigen that is highly expressed in prostate cancer. AMG 509 is a potent bispecific XmAb 2+1 immune therapy designed to direct T-effector cells to STEAP1-expressing cells. AMG 509 contains two identical humanized anti-STEAP1 Fab domains that bind STEAP1-expressing cells, an anti-CD3 scFv domain that binds T cells, and an Fc domain, engineered to lack effector function, that extends serum half-life. In preclinical studies, AMG 509 induced potent and specific T-cell-mediated lysis of STEAP1-expressing cancer models.

Relation between measurable residual disease and morphologic relapse in AML.
Lauren Shih, MD
Poster session

Measurable residual disease (MRD) in AML portends a poor prognosis. The outcomes and treatments of MRD after an initial MRD negative complete remission (MRD- CR) are unclear.

Trial in progress: a phase II, multicenter, single-arm study of zanubrutinib (BGB-3111) in patients with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma intolerant of prior treatment with ibrutinib.
Mazyar Shadman, MD, MPH
Poster session

Ibrutinib (ibr), a Bruton tyrosine kinase inhibitor (BTKi), was shown to improve patient outcomes in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL); however, adverse events (AEs) were the most common reason for discontinuing ibr (50% and 63% of discontinuations in relapse/refractory (R/R) and frontline patients, respectively; Haematologica. 2018:103:874). Zanubrutinib, an approved BTKi for mantle cell lymphoma, was specifically engineered to optimize selectivity. Pooled clinical data from 6 zanubrutinib monotherapy trials in B-cell malignancies (N=682 patients; R/R CLL/SLL [n=91]) suggested that zanubrutinib monotherapy was well tolerated and demonstrated a low rate of treatment discontinuation from AEs (9%; Tam, EHA 2019). Presented here is a trial-in-progress that will evaluate whether zanubrutinib monotherapy may serve as a therapeutic option for patients with CLL/SLL who have become ibr intolerant.

Emerging clinical phenotype of bone metastatic urothelial cancer (mUC): Association of early osseous metastases (EOM) and outcomes.
Petros Grivas, MD
Poster session

Background: Outcomes of patients (pts) with mUC with EOM have not thoroughly been described in the age of immuno-oncology. We hypothesized that EOM is associated with worse outcomes when compared to pts with non-osseous metastases (NOM).

Methods: We used a multi-institutional database of pts with mUC who received systemic treatment (trt) between March 2005 and August 2019, to assess survival and palliative outcomes of pts with EOM vs NOM at the time of metastatic diagnosis (met dx). Wilcoxon rank-sum and chi-square tests were performed. Survival was estimated by Kaplan-Meier method, Cox regression analysis was performed.

Results: We identified 270 pts, 72% men, mean age 67 ± 11 years, 28% never smokers. At met dx, 27% (n = 72) had ≥ 1 EOM; these pts were more likely to have de novo metastases vs. those with recurrent metastases (42% vs 19%, p < 0.001). Pts with EOM were more likely to have a change or stop in 1st line trt due to clinical progression (30.6% vs 15.7%, p = 0.006), and received fewer total lines of systemic trt, median of 1.0 (1.0-5.0) vs. 2.0 (1.0-8.0), p = 0.05. Pts with EOM had shorter median overall survival (OS) vs. those with NOM, (6.1 vs 13.7 months, p < .0001), HR = 2.79 (95% CI:1.95-3.97, p < .0001). Median OS was shorter for pts with EOM who received 1st line immune checkpoint inhibitor (n = 14) vs platinum-based chemotherapy (n = 43), (1.6 vs 9.1 months, p = 0.003). Pts with EOM received higher opioid analgesic doses at the first and last oncology outpatient visits compared to pts with NOM with mean morphine milligram equivalent (MME) dose of 60 ± 91 vs 28 ± 65 at first visit, p = 0.004, and 171 ± 214 vs. 94 ± 229 at last visit, p < 0.001.

Conclusions: The presence of EOM in mUC is associated with worse outcomes vs. pts with NOM. Pts with EOM may benefit from 1st line platinum-based chemotherapy vs. checkpoint immunotherapy. Furthermore, pts with EOM experience more pain than pts with NOM and may benefit from early engagement with palliative care. Pts with EOM represent a population with a highly unmet need for systemic, targeted and/or radiation interventions. Molecular subtypes may further define these pts and analysis is planned. We encourage ongoing clinical trials to report outcomes in pts with EOM. A consensus on reporting of non-measurable disease is also needed.

Contrasting genomic profiles in post-systemic treatment metastatic sites (MET), pretreatment primary tumors (PT), and liquid biopsies (LB) of clinically advanced prostate cancer (PC).
Petros Grivas, MD
Poster session

Comprehensive genomic profiling (CGP) was done on pre-systemic treatment (pre) PT, post-treatment (post) MET sites and LB in PC to uncover differences in genomic alterations (GA) and potential impact on therapy selection.

Outcomes of patients (pts) with metastatic urothelial carcinoma (mUC) following discontinuation of enfortumab-vedotin (EV): Emergence of a new unmet need.
Petros Grivas, MD
Poster session

Enfortumab vedotin (EV) is an antibody drug conjugate recently approved to treat mUC following prior platinum and PD1/L1 inhibitors. The outcomes and patterns of therapy of pts following discontinuation of EV has yet to be studied.

A multicenter randomized phase II study of nivolumab in combination with gemcitabine/cisplatin or ipilimumab as first-line therapy for patients with advanced unresectable biliary tract cancer (BilT-01).
David Zhen, MD
Poster session

Patients (pts) with advanced biliary tract cancers (BTC) have poor prognosis with a median overall survival (OS) less than 12 months (mos). This randomized phase 2, multi-institutional, study was designed to investigate the role of combinational immunotherapy, using nivolumab (nivo) with gemcitabine (gem)/cisplatin (cis), or nivo with ipilimumab (ipi) in pts with untreated advanced BTC.

Assessing the potential cost-effectiveness of the addition of atezolizumab to first-line platinum chemotherapy in advanced urothelial cancer: Implications for value-based pricing.
Petros Grivas, MD
Poster session

Data from interim analysis of IMvigor130 trial showed that 1st line treatment of advanced urothelial cancer (aUC) with atezolizumab (Atezo) + platinum-based chemotherapy (PBC) significantly improved progression-free survival (PFS), but not overall survival (OS), vs PBC.

Infigratinib and treatment response in advanced/unresectable or metastatic urothelial carcinoma in first-line and later-line treatment settings.
Petros Grivas, MD
Poster session

Infigratinib (BGJ398) is a potent and selective FGFR1–3 tyrosine kinase inhibitor (TKI), previously reported to be effective and well tolerated in patients with locally advanced/unresectable or metastatic urothelial carcinoma (mUC) bearing FGFR3 alterations [Pal et al. Cancer Discovery 2018]. However, this previous study did not examine differences in infigratinib activity based on number of prior lines of treatment (LOT). 

Assessing readmission after axicabtagene ciloleucel immunotherapy.
Paula Perkins, PA-C
Poster session

Axicabtagene ciloleucel (axi-cel) is an FDA approved CD19 targeted CAR-T for patients (pts) with diffuse-large-B cell lymphoma (DLBCL) after 2 lines of treatment. Pts are monitored inpatient for minimum 7 days after CAR-T infusion but remain at risk of complications after discharge that can lead to readmission. We report our institutional experience on the rate and etiology of readmissions after initial discharge.

KITE-439: A phase I study of HPV16 E7 T cell receptor-engineered T cells in patients with relapsed/refractory HPV16-positive cancers.
Sylvia Lee, MD
Poster session

Human papillomavirus 16 (HPV16) is the most prominent subtype across invasive head and neck cancers, as well as cervical cancer and other anogenital cancers (Saraiya M, et al. J Natl Cancer Inst. 2015). The HPV16 E7 (E7) viral antigen is important for the survival of HPV-positive tumor cells but is absent from normal human tissue, making it an attractive target for anti-cancer therapy. Preclinical efficacy has been observed with MHC class I-restricted T cell receptor (TCR)-engineered T cells targeting E7 on HPV16-positive tumor cells (Jin BY, et al. JCI Insight. 2018). This Phase 1, first-in-human, open-label, multicenter study (NCT03912831) will evaluate the safety and efficacy of KITE-439, an autologous TCR-engineered T cell therapy targeting E7, in HLA-A*02:01–positive patients with relapsed/refractory HPV16-positive cancers.

RESTORE: A single-arm, open-label phase II trial of bipolar androgen therapy (BAT) in men with metastatic castration resistant prostate cancer (mCRPC)—a comparison of post-abiraterone (Abi) versus post-enzalutamide (Enza) patients (Pts).
Michael Schweizer, MD
Poster session

A paradoxical inhibition of cell growth has been observed in both androgen-sensitive and castration resistant prostate cancer cell lines following the addition of high-dose testosterone.We have conducted several clinical trials investigating a mode of supraphysiologic testosterone therapy termed, BAT, in which testosterone levels are rapidly driven to the supraphysiologic range followed by a return to near-castrate levels over 28-day treatment cycles with favorable results. We previously reported the efficacy of BAT in mCRPC pts that were progressing on enza. In this study, we compared the effect of BAT in mCRPC pts whose last therapy was abi vs. enza. In addition, we examined the benefit of abi or enza rechallenge after progression on BAT.

Pembrolizumab (pembro) plus olaparib in patients (pts) with docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort A efficacy, safety, and biomarker results.
Evan Yu, MD
Poster session

Pembro + olaparib has shown antitumor activity and acceptable safety in docetaxel-pretreated pts with mCRPC enrolled in cohort A of the phase I/II KEYNOTE-365 study (NCT02861573). Updated results with new biomarker data are reported.

Tumor-informed assessment of molecular residual disease and its incorporation into practice for patients with early and advanced-stage colorectal cancer (CRC-MRD Consortia).
Stacey Cohen, MD
Poster session

Circulating tumor DNA (ctDNA) testing can be used for the assessment of molecular residual disease (MRD) in patients with early-stage or advanced colorectal cancer (CRC). Prospective evaluation of this methodology in clinical practice has been limited to-date.

A phase I dose-escalation trial of alpha-tocopheryloxyacetic acid and concurrent trastuzumab in patients with treatment refractory HER2+ metastatic breast cancer.
William R. Gwin, MD
Poster session

Metastatic HER2+ breast cancer, while initially responsive to trastuzumab, pertuzumab, and TDM-1, eventually progresses. The FDA recently approved trastuzumab deruxtecan, showing benefit in progression free survival but not in overall survival to date. Thus, additional therapies are needed for patients who progress on these HER2 directed agents. In metastatic HER2+ breast cancer, HER2-specific Th1 immune responses and higher CD4+ Th1 and CD8+ TIL levels are associated with a survival benefit. As this Type 1 immunity occurs in a minority of patients, additional immune modulation is needed. Alpha-tocopheryloxyacetic acid (α-TEA) has been reported to augment Type 1 immunity through increasing activated effector memory CD4+ and CD8+ T cells and decreasing immune suppressive CD4+CD25+ regulatory T cells in the tumor microenvironment. When given concurrently with an anti-HER2 antibody (7.16.4) in a pre-clinical tumor model, α-TEA synergized with 7.16.4 to induce tumor regression. We hypothesize that α-TEA and trastuzumab combination therapy in metastatic HER2+ breast cancer will be well tolerated, induce a clinical response, and augment anti-tumor Th1 immunity.

Concordance between independent and investigator assessment of disease-free survival (DFS) in the APACT trial.
E. Gabriela Chiorean, MD
Poster session

APACT was a phase III trial of adjuvant nab-paclitaxel + gemcitabine (nab-P + Gem) vs Gem alone in patients with resected pancreatic cancer (PC) and the first adjuvant PC trial to use independently assessed DFS as the primary endpoint (DFS by investigator review was a prespecified sensitivity analysis). We examined concordance between independent and investigator DFS review.

Primary adult retroperitoneal sarcoma (RS): Comprehensive genomic profiling (CGP) study.
Petros Grivas, MD, PhD
Poster session

We performed CGP on 315 cases of RS to discover targetable genomic alterations (GA) and their potential impact on potential targeted and immunotherapy (IO) selection.

Pembrolizumab (pembro) plus enzalutamide (enza) in patients (pts) with abiraterone acetate (abi)-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort C efficacy, safety, and biomarker results.
Evan Yu, MD
Poster session

Pembro + enza (cohort C) has shown antitumor activity and acceptable safety in abi-pretreated pts with mCRPC in the phase I/II KEYNOTE-365 study (NCT02861573). Updated results with new biomarker data from cohort C are reported.

Cost implications of clinical trial (CT) participation in metastatic non-small cell lung cancer (NSCLC).
Cristina Merkhofer, MD
Poster session

To assess the value of CTs in advanced NSCLC from the payer perspective, we compared insurance-related total direct medical costs for NSCLC patients who enrolled in CTs vs. those who did not.

Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB).
Jennifer M. Specht, MD
Poster session

Tucatinib (TUC) is an investigational TKI, highly selective for HER2 without significant inhibition of EGFR. HER2CLIMB is a randomized trial of TUC vs placebo in combination with trastuzumab and capecitabine in patients (pts) with HER2+ breast cancer (NCT02614794, Murthy NEJM 2019). The most common G ≥3 adverse events (AEs) with higher incidence on the TUC arm (diarrhea, palmar-plantar erythrodysesthesia syndrome [PPE], and elevated liver enzymes) are described herein.

Comparative effectiveness of second-line (2L) single-agent atezolizumab (A), nivolumab (N), and pembrolizumab (P) in patients (Pts) with locally advanced or metastatic urothelial cancer (aUC) who progressed on platinum-based systemic chemotherapy (plat-ch
Petros Grivas, MD
Poster session

Five PD-1/L1 inhibitors (PDi) are approved for 2L therapy (Rx) for aUC after progression on plat-chemo, but none compared with each other in randomized trials. Here, we assessed comparative effectiveness of 2L PDi in real-world setting.

Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer.
Heather H. Cheng, MD
Poster session

The relevance of germline mutations in metastatic prostate cancer is well established; however, comparison of germline genetics in African American (AA) versus Caucasian (CA) men with metastatic prostate cancer (PCa) is limited.

Prognostic role of mid-treatment PET/CT and plasma cytokines in patients undergoing chemoradiation for locally advanced non-small cell lung cancer (LA-NSCLC).
Jing Zeng, MD
Poster session

Patients with unresectable LA-NSCLC are treated with concurrent chemoradiation (CRT) and consolidation immunotherapy with survival that range from months to years or even decades. Early predictive biomarkers have potential to identify patients who are unlikely to benefit from continuing standard of care therapy and require a change in management. We investigated biomarkers that are widely available (PET/CT scan and plasma cytokine levels) to develop early predictors (mid-CRT) of survival in a phase II clinical trial of chemoradiation for LA-NSCLC.

Early results of TROPHY-U-01 Cohort 2: Sacituzumab govitecan (SG) in platinum-ineligible patients (pts) with metastatic urothelial cancer (mUC) who progressed after prior checkpoint inhibitor (CPI) therapy.
Petros Grivas, MD
Poster session

SG is an antibody-drug conjugate consisting of a humanized monoclonal anti–Trop-2 antibody coupled to the cytotoxic agent, SN-38, via a unique hydrolyzable linker. The epithelial cell surface antigen, Trop-2, demonstrates greater expression between UC vs normal tissue, and is a promising target. 

Phase I study of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC).
Andrew Coveler, MD
Poster session

SEA-CD40 is an investigational non-fucosylated, humanized IgG1 monoclonal antibody directed against CD40, a co-stimulatory receptor expressed on antigen-presenting cells (APCs). Activation of CD40 on APCs upregulates cytokine production and co-stimulatory receptors, enhancing tumor antigen presentation to T cells. Preclinical data indicate that treatment of PDAC with chemotherapy in conjunction with a CD40 agonist could enhance antigen presentation and initiate an antitumor immune response (Byrne KT and Vonderheide RH, Cell Rep 2016;15, 2719–32). An ongoing Phase 1 study (SGNS40-001) is evaluating SEA-CD40 as monotherapy and in combination with pembrolizumab in patients with advanced solid or hematologic malignancies. A new cohort is enrolling to evaluate the combination of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in PDAC.

First-line pembrolizumab (pembro) monotherapy in advanced clear cell renal cell carcinoma (ccRCC): Updated follow-up for KEYNOTE-427 cohort A.
Scott S. Tykodi, MD, PhD
Poster session

KEYNOTE-427 (NCT02853344), an open-label, single-arm, phase 2 study, showed clinical activity of first-line pembro monotherapy in patients (pts) with ccRCC (cohort A). Previous studies in RCC and immune-oncology suggest depth of response may correlate with long-term benefit. Association between depth of response and OS, along with updated efficacy and safety for cohort A of KEYNOTE-427, are presented.

Relevance of bone marrow biopsies for response assessment in NCTN follicular lymphoma clinical trials.
Mazyar Shadman, MD, MPH
Poster session

Bone marrow biopsies (BMB) are performed pre/post therapy to confirm complete response (CR) in patients (pts) with lymphoma on clinical trials. We evaluated 2 prior data sets and concluded that BMB impact response assessment in a minority of pts with follicular lymphoma (FL) (Rutherford BJH 2017; Rutherford ASH abstract 1605, 2018). We sought to establish if BMB add value in assessing response or identify distinct progression free (PFS) or overall survival (OS) outcomes in a large, multicenter, multi-trial cohort.

Comprehensive genomic profiling (CGP) of histologic subtypes of urethral carcinomas (UrthCa).
Petros Grivas, MD
Poster session

UrthCa is an uncommon GU malignancy that can progress to advanced metastatic disease.

Pembrolizumab (pembro) plus docetaxel and prednisone in patients (pts) with abiraterone acetate (abi) or enzalutamide (enza)-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort B efficacy, safety and, biomarker results.
Evan Yu, MD
Poster session

Pembro + docetaxel and prednisone (cohort B) has shown antitumor activity in pts with mCRPC in the phase I/II KEYNOTE-365 study (NCT02861573). Updated efficacy and safety and new biomarker data from cohort B are reported.

Implementation of systematic germline genetic testing (GT) for metastatic prostate cancer (mPC) patients at the Puget Sound VA prostate oncology clinic.
Alexandra Sokolova, MD
Poster session

There is increasing clinical relevance for GT in patients with mPC to evaluate the 2-fold possibilities of molecularly targeted therapies and implications for relatives. NCCN guidelines recommend GT for subsets of men, including those with mPC. While exciting, there are new logistical challenges around workflows for delivering GT services. We sought to address these challenges through a prospective pilot study designed to systematically deliver GT to all men with mPC receiving care at the Puget Sound VA prostate cancer (PUG-VA PC) Clinic. Our hypothesis was that systematic universal GT for men with mPC would identify similar prevalence rates of germline pathogenic/likely pathogenic variants (P/LPV) among veterans compared to previously reported cohorts.

Speakers
More than 20 members of our leading-edge research team will be sharing their latest findings. Here are some of the highlights.
E. Gabriela Chiorean, MD
  • Clinical Research Director, Gastrointestinal Medical Oncology, University of Washington Medical Center
  • Professor of Medicine, University of Washington School of Medicine

Colorectal, gastrointestinal, hepatobiliary, and pancreatic cancers as well as Phase I clinical studies

SWOG S1505: Results of perioperative chemotherapy (peri-op CTx) with mfolfirinox versus gemcitabine/nab-paclitaxel (Gem/nabP) for resectable pancreatic ductal adenocarcinoma (PDA)
SWOG S1505: Results of perioperative chemotherapy (peri-op CTx) with mfolfirinox versus gemcitabine/nab-paclitaxel (Gem/nabP) for resectable pancreatic ductal adenocarcinoma (PDA)
Oral abstract session

Clinical outcomes after curative treatment of resectable PDA remain suboptimal. To assess the potential of early control of systemic disease with multiagent peri-op CTx, we conducted a prospective trial in the National Clinical Trials Network.

Julie R. Gralow, MD
  • Director, Breast Medical Oncology, Seattle Cancer Care Alliance
  • Clinical Research Division, Member, Fred Hutchinson Cancer Research Center 
  • Professor, Medical Oncology Division, University of Washington School of Medicine

Investigational Breast Cancer Treatments, Chemotherapy, Hormonal Therapy, Biologically Targeted Therapies

Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC).
Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC).
Oral abstract session

The standard of care for HER2-positive EBC is chemotherapy plus one year of HER2-directed therapy. However, recurrence—particularly in high-risk populations—remains a problem, as does systemic chemotherapy-associated toxicity. In KAITLIN, we aimed to improve efficacy and reduce toxicity by replacing taxanes and trastuzumab with T-DM1.

Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416).
Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416).
Oral abstract session

PARP inhibitors(i) are effective in BRCA-mutation-associated metastatic breast cancer(MBC). However, there are no studies evaluating PARPi + platin chemotherapy in BRCA wild-type(wt) TNBC. Approximately 1/2 of BRCAwt TNBC demonstrate homologous recombination deficiency (HRD) resulting in a BRCA-like phenotype which might render them sensitive to PARPi. S1416 compared the efficacy of cisplatin plus PARPi veliparib (Vel) or placebo (P) in 3 groups of MBC: gBRCA+; BRCA-like; and non-BRCA-like.

Petros Grivas, MD, PhD
  • Clinical Director, Genitourinary Cancers Program, University of Washington Medicine
  • Associate Professor, Department of Medicine, Division of Oncology, University of Washington School of Medicine
Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis.
Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis.
Plenary session: May 31

Platinum-based chemotherapy is an active 1L regimen for advanced UC; however, progression-free survival (PFS) and overall survival (OS) are generally short because of chemotherapy resistance. This randomized, phase 3 trial (JAVELIN Bladder 100; NCT02603432) evaluated avelumab (anti–PD-L1) as maintenance therapy following response or stable disease with 1L platinum-based chemotherapy in patients with advanced UC.

Clinical impact of COVID-19 on patients with cancer: Data from the COVID-19 and Cancer Consortium (CCC19).
Clinical impact of COVID-19 on patients with cancer: Data from the COVID-19 and Cancer Consortium (CCC19).
Clinical science symposium

There are limited data on COVID-19 in patients with cancer. We characterize the outcomes of patients with cancer and COVID-19 and identify potential prognostic factors.

IMvigor010: Primary analysis from a phase III randomized study of adjuvant atezolizumab (atezo) versus observation (obs) in high-risk muscle-invasive urothelial carcinoma (MIUC).
IMvigor010: Primary analysis from a phase III randomized study of adjuvant atezolizumab (atezo) versus observation (obs) in high-risk muscle-invasive urothelial carcinoma (MIUC).
Oral abstract session

Radical surgery ± cisplatin-based neoadjuvant chemo (NAC) is the mainstay treatment (tx) for MIUC, with no conclusive level 1 evidence for adjuvant chemo (AC). Here we present the primary analysis from IMvigor010, a global, open-label, multicenter, randomized trial of adjuvant atezo (anti–PD-L1; approved in metastatic UC [mUC] settings) in pts with MIUC at high risk of recurrence following primary resection.

William P. Harris, MD
  • Associate Professor, Division of Oncology, University of Washington School of Medicine
  • Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center

Gastrointestinal cancers including liver, bile duct, pancreas, colon, rectal, anal, gastric, esophageal, and neuroendocrine tumors.

Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC).
Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC).
Oral abstract session

The combination of dual immune checkpoint inhibitors (ICI) T (anti–CTLA-4) and D (anti–PD-L1) showed tolerability with a promising objective response rate (ORR) in the initial cohort of this study (NCT02519348). Subsequent evaluation of pts with solid tumors treated with increasing doses of T suggested priming with a higher dose of T may induce a stronger immune response and enhance anti-tumor activity. Thus, the randomized expansion cohorts comprised 4 arms evaluating T and D as monotherapies and 2 T+D regimens, including a novel T+D regimen featuring a single, priming dose of T.

Veena Shankaran, MD, MS
  • Associate Professor, Medical Oncology, University of Washington School of Medicine
  • Assistant Member, Clinical Research Division, Fred Hutchinson Cancer Research Center

All gastrointestinal cancers including gastric, esophageal, colon, rectal, pancreas, and neuroendocrine tumors; primary clinical interest in cancers of the stomach and esophagus
 

Cumulative incidence of financial hardship in metastatic colorectal cancer patients: Primary endpoint results for SWOG S1417CD.
Cumulative incidence of financial hardship in metastatic colorectal cancer patients: Primary endpoint results for SWOG S1417CD.
Poster discussion session

Despite evidence that rising cancer care costs are contributing to “financial toxicity” in cancer pts, no studies, to our knowledge, have prospectively assessed the financial impact of cancer diagnosis (dx) using both self-reported and objective financial measures. S1417CD, led by the SWOG Cancer Research Network and conducted in the NCI Community Oncology Research Program (NCORP), was the first national prospective cohort study to evaluate time-to-first evidence of major financial hardship (MFH) in pts with newly diagnosed mCRC. We present results of the primary endpoint analysis.

Scott S. Tykodi, MD, PhD
  • Assistant Member, Clinical Research Division, Fred Hutchinson Cancer Research Center
  • Associate Professor, Division of Medical Oncology, University of Washington School of Medicine

Cancer immunotherapy, renal cell carcinoma, kidney cancer, melanoma, clinical trials
 

FRACTION-RCC: Innovative, high-throughput assessment of nivolumab + ipilimumab for treatment-refractory advanced renal cell carcinoma (aRCC).
FRACTION-RCC: Innovative, high-throughput assessment of nivolumab + ipilimumab for treatment-refractory advanced renal cell carcinoma (aRCC).
Oral abstract session

The immuno-oncology (I-O) combination nivolumab + ipilimumab (NIVO+IPI) is approved for first-line (1L) and NIVO is approved for second-line treatment post TKI therapy in aRCC. The open-label, randomized, phase 2 Fast Real-Time Assessment of Combination Therapies in Immuno-Oncology (FRACTION-RCC; NCT02996110) platform study has an adaptive design allowing rapid evaluation of I-O therapies, including NIVO+IPI or other investigational combinations. This FRACTION analysis reports preliminary outcomes with NIVO+IPI in aRCC pts after progression on checkpoint inhibitor therapy.

Clinical Trials
A Trial of Endocrine Response in Women with Invasive Lobular Breast Cancer
Hannah M. Linden, MD
NCT02206984

To study whether fulvestrant is more effective than anastrozole or tamoxifen in reducing Ki67 in ILC and whether that Ki67 reduction will correlate with alterations in expression of ER and ER-regulated genes. Differential Ki67 effect in this study will serve as a surrogate for outcome of ILC patients on endocrine therapy.
A phase III, multicenter, randomized, open-label trial to evaluate efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, early breast cancer (New Adjuvant TriAl with Ribociclib [LEE011]: NATALEE).
Rachel L. Yung, MD
NCT03701334

A phase III multi-center, randomized, open-label trial to evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with HR+/HER2- Early Breast Cancer
A multicenter, non-randomized, open-label dose escalation Phase Ib study of regorafenib in combination with pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) with no prior systemic therapy
William P. Harris, MD
NCT03347292

This study will determine if the combination of regorafenib and pembrolizumab is safe and tolerated in patients with advanced liver cancer. In addition, the study will explore the anti-tumor activity of this combination as well as potentially identifying blood and tissue biomarkers associated with disease activity, status or response. The study will also investigate how the drugs behave in your body

A Phase III Randomized, Double-Blind, Placebo-Controlled, Multi-Regional, International Study of Durvalumab in Combination with Gemcitabine plus Cisplatin versus Placebo in Combination with Gemcitabine plus Cisplatin for Patients with First-Line Advanced Biliary Tract Cancers (TOPAZ-1)

David Zhen, MD
NCT03875235

Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1)
Dual Immune Checkpoint Blockade and Hypofractionated Radiation in Patients with Salivary Gland Cancers
Cristina P. Rodriguez, MD
NCT03749460

This phase I/II trial studies the side effects and how well nivolumab and ipilimumab works when given together with stereotactic body radiation therapy (SBRT) in treating patients with salivary gland cancers. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. SBRT is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Giving nivolumab and ipilimumab and SBRT may work better in treating patients with advanced salivary gland cancers.
A Biomarker-Directed Phase 2 Platform Study in Patients with Advanced Non-Small Cell Lung Cancer whose Disease has Progressed on First-Line Osimertinib Therapy
Christina S. Baik, MD, MPH
NCT03944772

Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer who progressed on First-Line Osimertinib Therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.
A MULTICENTER, OPEN-LABEL PHASE 1 STUDY OF U3-1402 IN SUBJECTS WITH METASTATIC OR UNRESECTABLE EGFR-MUTANT NON-SMALL CELL LUNG CANCER
Christina S. Baik, MD, MPH
NCT03260491

This study has two parts: dose escalation and dose expansion. The primary objectives are: •For Dose Escalation, to assess the safety and tolerability of U3-1402 in the study population and to determine the recommended dose for expansion of U3-1402 in the study population •For Dose Expansion, to investigate the antitumor activity of U3-1402 The number of treatment cycles is not fixed in this study. Participants will continue study treatment (for approximately 36 months) until they decide not to (withdraw consent), their disease gets worse [progressive disease (PD)], or side effects become unacceptable (unacceptable toxicity) or other stopping reasons have been met.
Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer (Study SWOG/NRG 1806)
Petros Grivas, MD, PhD
NCT03775265

This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.
A Randomized, Double-Blind, Controlled Phase 3 Study of Cabozantinib in Combination with Nivolumab and Ipilimumab versus Nivolumab and Ipilimumab in Subjects with Previously Untreated Advanced or Metastatic Renal Cell Carcinoma of Intermediate or Poor Risk
Scott S. Tykodi, MD, PhD
NCT03937219

This is a multicenter, randomized, double-blinded, controlled Phase 3 trial of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in combination with matched placebo. Approximately 676 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio (~338 per treatment arm) at approximately 150 sites.
A Phase 1/2 Study of ABI-009 (Nab-Rapamycin) with Pazopanib (VOTRIENT®) in Patients with Advanced Nonadipocytic Soft-Tissue Sarcomas
Lee D. Cranmer, MD, PhD, FACP
NCT03660930

This phase I/II trial studies the side effects and best dose of nanoparticle albumin-bound rapamycin and how well it works with given together with pazopanib hydrochloride in treating participants with nonadipocytic soft tissue sarcomas. Nanoparticle albumin-bound rapamycin and pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
A Pilot Study of Oraxol in Subjects with Cutaneous Angiosarcoma
Michael J. Wagner, MD
NCT03544567

This is a non-blinded, multi-center, open-label, pilot study to evaluate the activity, safety, and tolerability of Oraxol in subjects with cutaneous angiosarcoma.
A Phase 1 Open-label, Multicenter Study Evaluating the Safety and Pharmacokinetics of Escalating Doses of IGM-2323 in Subjects with Relapsed/Refractory Non-Hodgkin Lymphomas
Ajay K. Gopal, MD
NCT04082936

This is a Phase 1 study of IGM-2323 in adult subjects with relapsed or refractory B-cell Non-Hodgkin Lymphoma. This study will consist of a dose-escalation stage and a dose-expansion stage where subjects will be enrolled into indication-specific expansion cohorts. IGM-2323 will be administered intravenously (IV). Additional CD20-positive NHL histologies (e.g. MZL and MCL), may be allowed with Medical Monitor approval during the Dose-Escalation Phase of the study.
Phase II Study of Anti-CD20 Antibody Therapy Plus Pembrolizumab (MK-3475) in Subjects with Relapsed Follicular and Diffuse Large B-Cell Lymphoma
Stephen D. Smith, MD
NCT03401853

This phase II trial studies how well rituximab and pembrolizumab work in treating patients with follicular lymphoma or diffuse large B cell lymphoma that has come back or does not respond to treatment. Monoclonal antibodies, such as pembrolizumab and rituximab, may interfere with the ability of cancer cells to grow and spread.

An Open-Label, Randomized, Multicenter, Phase Ib/II Trial Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosentuzumab (BTCT4465A) in Combination with Polatuzumab Vedotin in Patients with B-Cell Non-Hodgkin Lymphoma

Stephen D. Smith, MD
NCT03671018

This study will evaluate the safety, tolerability, pharmacokinetics, and efficacy of mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large B-cell lymphoma (DLBCL) and in participants with follicular lymphoma (FL). It will consist of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with relapsed or refractory (R/R) DLBCL and 2L+ R/R FL.
A Pilot Trial of Adriamycin, Pembrolizumab, Vinblastine and Dacarbazine (APVD) for Patients with Untreated Classical Hodgkin Lymphoma
Ryan C. Lynch, MD
NCT03331341

This phase II trial studies the side effects of doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine in treating patients with classical Hodgkin Lymphoma. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Giving doxorubicin hydrochloride, pembrolizumab, vinblastine, and dacarbazine may work better in treating classical Hodgkin lymphoma.
A Two-Stage Phase 1 Open-Label Study of huJCAR014, CD19-targeted Chimeric Antigen Receptor (CAR)-Modified T cells Bearing a Human Binding Domain, in Adult Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma and Acute Lymphocytic Leukemia
Cameron J. Turtle, MBBS, PhD, FRACP, FRCPA
NCT03103971

This phase I trial studies the side effects of autologous human anti-CD19 chimeric antigen receptor (CAR)-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes (huJCAR014) in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma or acute lymphoblastic leukemia. huJCAR014 CAR-T cells are made in the laboratory by genetically modifying a patient's T cells and may specifically kill cancer cells that have a molecule CD19 on their surfaces.
A Phase I Study Evaluating Copanlisib in Combination with R-GCD (Gemcitabine, Carboplatin, Dexamethasone, and Rituximab) with Relapsed/Refractory Diffuse Large B-Cell Lymphoma and High-Risk Follicular Lymphoma
Ryan C. Lynch, MD
NCT04156828

This phase I trial studies the best dose of copanlisib when given together with combination chemotherapy (R-GCD) in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory) or grade 3b follicular lymphoma that has come back (relapsed) after 1 prior line of therapy. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as rituximab, gemcitabine, carboplatin, and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving copanlisib together with R-GCD as second line therapy may improve the complete response rate for patients with diffuse large B-cell lymphoma or follicular lymphoma.
Individualized Treatment for Relapsed/Refractory Multiple Myeloma Based on High Throughput Drug Sensitivity and Genomics Data
Andrew J. Cowan, MD
NCT03389347

This pilot clinical trial studies whether using high throughput drug sensitivity and genomics data is feasible in developing individualized treatment in patients with multiple myeloma or plasma cell leukemia that has come back or does not respond to treatment. High throughput screen tests many different drugs that kill multiple myeloma cells in individual chambers at the same time. Matching a drug or drug combination to a patient using high throughput screen and genetic information may improve the ability to help patients by choosing drugs that work well for their disease.
Addition of Sorafenib to G-CSF, Cladribine, Cytarabine and Mitoxantrone (G-CLAM) in Adults with Newly-Diagnosed Acute Myeloid Leukemia (AML) Independent of FLT3-ITD status: A Phase 1/2 Study
Anna B. Halpern, MD
NCT02728050

This phase I/II trial studies the side effects and best dose of filgrastim (granulocyte colony-stimulating factor [G-CSF]), cladribine, cytarabine, and mitoxantrone hydrochloride, when given together with sorafenib tosylate and to see how well they work in treating patients with newly-diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome (likely to be more aggressive). Drugs used in chemotherapy, such as filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride together with sorafenib tosylate may kill more cancer cells.
A Single-Center Phase 1/2 Study of Single- or Fractioned-Dose Gemtuzumab Ozogamicin in Combination with G-CSF, Cladribine, Cytarabine and Mitoxantrone (GCLAM) for Previously Untreated Adult Acute Myeloid Leukemia or High-Grade Myeloid Neoplasm
Roland B. Walter, MD, PhD, MS
NCT03531918

This phase I/II trial studies the side effects and best dosing frequency of gemtuzumab ozogamicin when given in combination with granulocyte colony stimulating factor (G-CSF), cladribine, cytarabine and mitoxantrone (GCLAM) and to see how well they work in treating participants with acute myeloid leukemia or high-grade myeloid tumors (neoplasms) that have not been previously treated. Antibody-drug conjugates, such as gemtuzumab ozogamicin, act by directly delivering toxic chemotherapy to cancer cells. Granulocyte colony stimulating factor is a growth factor used to stimulate leukemia cells and render them more sensitive to chemotherapy drugs. Drugs used in chemotherapy, such as cladribine, cytarabine and mitoxantrone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving gemtuzumab ozogamicin in combination with G-CSF, cladribine, cytarabine and mitoxantrone hydrochloride may work better in treating participants with acute myeloid leukemia or high-grade myeloid neoplasm.
A phase 2 trial of fractionated gemtuzumab ozogamicin to eradicate measurable residual disease in acute myeloid leukemia patients (GO for MRD)
NCT03737955

This phase II trial studies how well fractionated gemtuzumab ozogamicin works in treating measurable residual disease in participants with acute myeloid leukemia. Antibody-drug conjugates, such as gemtuzumab ozogamicin, may block cancer growth in different ways by targeting certain cells.
A Phase I Study of B-cell Maturation Antigen (BCMA)-Specific Chimeric Antigen Receptor T cells in Combination with JSMD194, a Small Molecule Inhibitor of Gamma Secretase, in Patients with Relapsed or Persistent Multiple Myeloma
Andrew J. Cowan, MD
NCT03502577

This phase I trial determines the side effects and best dose of B-cell maturation antigen (BCMA)-chimeric antigen receptor (CAR) T-cells when combined with gamma-secretase inhibitor LY3039478 (LY3039478), cyclophosphamide, and fludarabine in treating participants with multiple myeloma that that has come back or remains despite treatment. Placing genes added in the laboratory into immune T-cells may make the T-cells recognize BCMA, a protein on the surface of cancer cells. LY3039478 may enhance the killing of cancer cells by increasing the BCMA expression on multiple myeloma cells, making the targeted BCMA CAR-T treatment more effective. LY3039478 also decreases the amount of BCMA found in the circulation (called soluble BCMA) that is not bound to the myeloma cells. LY3039478 can therefore reduce the potential for soluble BCMA to act as a decoy. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BCMA CAR T therapy with LY3039478, cyclophosphamide, and fludarabine may work better in treating participants with relapsed or persistent multiple myeloma.

A Phase II, Single Arm Study Assessing the Efficacy of Osimertinib in Combination with Savolitinib in Patients with EGFRm+ and MET+, Locally Advanced or Metastatic Non-Small Cell Lung Cancer who have Progressed Following Treatment with Osimertinib (The SAVANNAH Study)

Christina S. Baik, MD, MPH
NCT03778229

This study (the SAVANNAH study) will investigate the efficacy of osimertinib in combination with savolitinib in patients with EGFRm+ and MET+, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib.
A Phase II Randomized Controlled Trial Comparing Four GVHD-Reduction Strategies for Allogeneic Peripheral Blood Transplantation (PBSCT) for Patients with Acute Leukemia: Selective Depletion of CD45RA+ Naïve T Cells (TND) vs. CD34+-Selected Pan T Cell Depletion (CD34+) vs. Post-Transplantation Cyclophosphamide (PTCy) vs. Tacrolimus and Methotrexate (TacMTX) PBSCT.
Marie E. Bleakley, MD, PhD, MMSC
NCT03970096

This phase II trial compares four strategies for the reduction of graft versus host disease in patients with acute leukemia in remission. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patients immune system from rejecting the donors stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patients bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient immune cells and help destroy any remaining cancer cells.
Phase I Study of Adoptive Immunotherapy with CD8+ and CD4+ Memory T cells Transduced to Express an HA-1-specific T cell Receptor (TCR) for Children and Adults with Recurrent Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation (HCT)
Elizabeth F. Krakow, MD, MSc
NCT03326921

This phase I trial studies the side effects and best dose of CD4+ and CD8+ HA-1 T cell receptor (TCR) T cells in treating patients with acute leukemia that has come back or does not respond to treatment following donor stem cell transplant. T cell receptor is a special protein on T cells that helps them recognize proteins on other cells including leukemia. HA-1 is a protein that is present on the surface of some peoples' blood cells, including leukemia. HA-1 T cell immunotherapy enables genes to be added to the donor cells to make them recognize HA-1 markers on leukemia cells.

A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphomas

Mazyar Shadman, MD, MPH
NCT03277729

The purpose of this research is to find the best dose of genetically modified T-cells, to study the safety of this treatment, and to see how well it works in treating patients with B cell non-Hodgkin lymphoma that has come back or did not respond to previous treatment.
A PHASE I OPEN LABEL, MULTICENTER STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI-TUMOR ACTIVITY OF ZN-c5 ALONE AND IN COMBINATION WITH PALBOCICLIB IN SUBJECTS WITH PREVIOUSLY TREATED ESTROGEN-RECEPTOR POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2 NEGATIVE ADVANCED BREAST CANCER
Hannah M. Linden, MD
NCT03560531

This is a Phase 1/2, open-label, multicenter, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ZN-c5 administered orally in subjects with advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer. ZN-c5 will be evaluated both as monotherapy and in combination with palbociclib (IBRANCE)
ATTAC-MCC: Phase I/II study of Autologous CD8+ and CD4+ Transgenic T cells expressing high affinity MCPyV-specific TCRs combined with Avelumab and Class I MHC -upregulation in patients with metastatic MCC refractory to PD-1 axis blockade
Joshua Veatch, MD, PhD
NCT03747484

This phase I/II trial studies the side effects of gene-modified immune cells (FH-MCVA2TCR) and to see how well they work in treating patients with Merkel cell cancer that has spread to other parts of the body (metastatic) or that cannot be removed by surgery (unresectable). Placing a gene that has been created in the laboratory into immune cells may improve the body's ability to fight Merkel cell cancer.
A Phase II Open-label Study of UM171 Expanded Cord Blood Transplantation in Patients with High and Very High Risk Acute Leukemia/Myelodysplasia
Filippo Milano, MD, PhD
NCT03913026

Allogeneic hematopoietic stem cell transplantation is a life-saving procedure in patients with blood cancers. Cord blood (CB) represents an alternative source of stem cells, which is associated with a lower risk of relapse, especially in the presence of minimal residual disease in the setting of acute leukemia and myelodysplasia. Furthermore, CB has the added advantage of being associated with a low risk of chronic graft versus host disease (GVHD). Unfortunately, CB transplants are hampered by a higher risk of transplant related mortality (TRM) when compared to bone marrow/peripheral blood transplants because of the limited cell dose of CB. In the previous UM171 trial (NCT02668315), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe. UM171 expanded CB was associated with a median neutrophil recovery at day (D)+18 post transplant. Amongst 22 patients who received a single UM171 CB transplant with a median follow-up of 18 months, risk of TRM (5%) and grade 3-4 acute GVHD (10%) were low. There was no moderate-severe chronic GVHD. Thus, overall and progression free survival at 12 months were impressive at 90% and 74%, respectively. The UM171 expansion protocol allowed access to smaller, better HLA matched CBs as >80% of patients received a 6-7/8 HLA matched CB. Interestingly there were 5 patients who had already failed an allogeneic transplant and 5 patients with refractory/relapsed acute leukemia/aggressive lymphoma. Despite this high risk population, progression was 20% at 12 months. Hence, in this new trial, investigators are targeting patients with high and very high-risk acute leukemia/myelodysplasia to test the antileukemia effect of this new graft, a UM171 expanded CB.
A Phase 3, Randomized, Double-Blind Study of Pamrevlumab or Placebo in Combination With Gemcitabine Plus Nab-paclitaxel (G/NP) as Neoadjuvant Treatment in Patients With Locally Advanced, Unresectable Pancreatic Cancer
NCT03941093

This is a Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of neoadjuvant treatment with pamrevlumab or placebo in combination with gemcitabine plus nab-paclitaxel (G/NP) in the treatment of locally advanced, unresectable pancreatic cancer subjects.
A Study Evaluating Escalating Doses of 211At-labeled anti-CD45 MAb BC8-B10 (211At-BC8-B10) followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS)
Brenda M. Sandmaier, MD
NCT03128034

This phase I/II trial studies the side effects and best dose of 211^astatine(At)-BC8-B10 before donor stem cell transplant in treating patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Radioactive substances, such as astatine-211, linked to monoclonal antibodies, such as BC8, can bind to cancer cells and give off radiation which may help kill cancer cells and have less of an effect on healthy cells before donor stem cell transplant.
A Randomized Phase II Study to Compare the Net Clinical Benefit of Cyclosporine and Sirolimus combined with MMF or Post-Transplant Cyclophosphamide as GVHD Prophylaxis after HLA-Matched or HLA-Mismatched Unrelated G-CSF Mobilized Blood Cell Transplantation using Nonmyeloablative or Reduced Intensity Conditioning for Patients with Hematologic Malignancies: A Multi-Center Trial
Masumi Ueda, MD
NCT03246906

This randomized phase II trial includes a blood stem cell transplant from an unrelated donor to treat blood cancer. The treatment also includes chemotherapy drugs, but in lower doses than conventional (standard) stem cell transplants. The researchers will compare two different drug combinations used to reduce the risk of a common but serious complication called "graft versus host disease" (GVHD) following the transplant. Two drugs, cyclosporine (CSP) and sirolimus (SIR), will be combined with either mycophenolate mofetil (MMF) or post-transplant cyclophosphamide (PTCy). This part of the transplant procedure is the main research focus of the study.
A Phase III, Randomized, Open-label Study to Evaluate Pembrolizumab as Neoadjuvant Therapy and in Combination With Standard of Care as Adjuvant Therapy for Stage III-IVA Resectable Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA HNSCC)
Cristina P. Rodriguez, MD
NCT03765918

This is a randomized, active-controlled, open-label study of pembrolizumab (Pembro) given prior to surgery and pembrolizumab in combination with standard of care radiotherapy (with or without cisplatin), as post-surgical therapy in treatment naïve participants with newly diagnosed Stage III/IVA, resectable, locoregionally advanced, head and neck squamous cell carcinoma (LA-HNSCC). The primary hypothesis is that pembrolizumab given before surgery and after surgery in combination with radiotherapy (with or without cisplatin) improves major pathological response and event-free survival compared to radiotherapy (with or without cisplatin) alone.
A Phase I Study of Adoptive Immunotherapy for Advanced B-cell Maturation Antigen (BCMA)+ Multiple Myeloma with Autologous CD4+ and CD8+ T cells Engineered to Express a BCMA-specific Chimeric Antigen Receptor
Damian J. Green, MD
NCT03338972

This phase I trial studies the side effects and best dose of BCMA CAR-T cells in treating patients with BCMA positive multiple myeloma that has come back or does not respond to treatment. T cells are a type of white blood cell and a major component of the immune system. T-cells that have been genetically modified in the laboratory express BCMA and may kill cancer cells with the protein BCMA on their surface. Giving chemotherapy before BCMA CAR-T cells may reduce the amount of disease and to cause a low lymphocyte (white blood cell) count in the blood, which may help the infused BCMA CAR-T cells survive and expand.
A Phase I/II Study Evaluating Escalating Doses of 211At-labeled anti-CD45 MAb BC8-B10 (211At-BC8-B10) followed by Related Haplo-identical Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Leukemia or Myelodysplastic Syndrome (MDS).
Phuong T. Vo, MD
NCT03670966

This phase I/II trial studies the side effects and best dose of astatine At 211 anti-CD45 monoclonal antibody BC8-B10 (211At-BC8-B10) followed by donor stem cell transplant in treating participants with acute myeloid leukemia, or acute lymphoblastic leukemia, or myelodysplastic syndrome that has come back or isn't responding to treatment. Monoclonal antibodies, such as 211At-BC8-B10, may interfere with the ability of cancer cells to grow and spread. Giving chemotherapy and total body irradiation before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the participant, they may help the participant's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells, called graft versus host disease. Giving cyclophosphamide, tacrolimus, mycophenolate mofetil, and sirolimus after a transplant may stop this from happening.
A Phase II Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients with Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Risk-Adjusted Chemotherapy Only Cytoreduction with Busulfan, Cyclophosphamide and Fludarabine
NCT02143830

The purpose of this study is to determine whether the use of lower doses of busulfan and the elimination of cyclosporine will further reduce transplant-related side effects for patients with Fanconi Anemia (FA). Patients will undergo a transplant utilizing mis-matched related or matched unrelated donors following a preparative regimen of busulfan, fludarabine, anti-thymocyte globulin and cyclophosphamide.

A Phase 1/2, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0005 in Patients with Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)

Christina S. Baik, MD, MPH
NCT03093116

Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
RCI BMT 16-NTCD/PBMTC GVH1701: Multi-center Phase II Randomized Controlled Trial of Naïve T Cell Depletion for Prevention of Chronic Graft-Versus-Host Disease in Children and Young Adults
Marie E. Bleakley, MD, PhD, MMSC
NCT03779854

This phase II trial studies how well naive T-cell depletion works in preventing chronic graft-versus-host disease in children and young adults with blood cancers undergoing donor stem cell transplant. This study is comparing naïve T-cell depletion transplantation to the traditional stem cell transplantation. In these transplants, chemotherapy and total-body radiotherapy ('conditioning') are used to kill residual leukemia cells and the patient's normal blood cells, especially immune cells that could reject the donor cells. Following the chemo/radiotherapy, blood stem cells from the donor are infused. These stem cells will grow and eventually replace the patient's original blood system, including red cells that carry oxygen to our tissues, platelets that stop bleeding from damaged vessels, and multiple types of immune-system white blood cells that fight infections. Mature donor immune cells, especially a type of immune cell called T lymphocytes (or T cells) are transferred along with these blood-forming stem cells. T cells are a major part of the curative power of transplantation because they can attack leukemia cells that have survived the chemo/radiation therapy and also help to fight infections after transplantation. However, donor T cells can also attack a patient's healthy tissues in an often-dangerous condition known as Graft-Versus-Host-Disease (GVHD). Drugs that suppress immune cells are used to decrease the severity of GVHD; however, they are incompletely effective and prolonged immunosuppression used to prevent and treat GVHD significantly increases the risk of serious infections. Removing all donor T cells from the transplant graft can prevent GVHD, but doing so also profoundly delays infection-fighting immune reconstitution and eliminates the possibility that donor immune cells will kill residual leukemia cells. Work in animal models found that depleting a type of T cell, called naïve T cells or T cells that have never responded to an infection, can diminish GVHD while at least in part preserving some of the benefits of donor T cells including resistance to infection and the ability to kill leukemia cells. This clinical trial studies how well the selective removal of naïve T cells works in preventing GVHD after peripheral blood stem cell transplants compared to the subjects that receive unmanipulated bone marrow transplants.
A Phase 2 Trial Of Pt2977 In Combination With Cabozantinib In Patientswith Advanced Clear Cell Renal Cell Carcinoma
Scott S. Tykodi, MD, PhD
NCT03634540

An open-label Phase 2 study of PT2977 in combination with cabozantinib in patients with advanced ccRCC.
Allogeneic Hematopoietic Cell Transplantation for Patients with Nonmalignant Inherited Disorders Using a Treosulfan Based Preparative Regimen
Lauri M. Burroughs, MD
NCT00919503

This phase II clinical trial studies how well treosulfan and fludarabine phosphate with or without low dose radiation before donor stem cell transplantation works in treating patients with nonmalignant (noncancerous) diseases. Hematopoietic cell transplantation has been shown to be curative for many patients with nonmalignant (noncancerous) diseases such as primary immunodeficiency disorders, bone marrow failure syndromes, hemoglobinopathies, and inborn errors of metabolism (metabolic disorders). Powerful chemotherapy drugs and/or radiation are often used to condition the patient before infusion of the new healthy donor cells. The purpose of the conditioning therapy is to destroy the patient's abnormal bone marrow which doesn't work properly in order to make way for the new healthy donor cells which functions normally. Although effective in curing the patient's disease, many hematopoietic cell transplantation regimens use intensive chemotherapy and/or radiation which can be quite toxic, have significant side effects, and can potentially be life-threatening. Investigators are investigating whether a new conditioning regimen that uses less intensive drugs (treosulfan and fludarabine phosphate) with or without low dose radiation results in new blood-forming cells (engraftment) of the new donor cells without increased toxicities in patients with nonmalignant (noncancerous) diseases.
A Pilot Feasibility Study of Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants Using a Self-Inactivating Lentiviral Vector to Transduce Autologous CD34+ Hematopoietic Cells
Aleksandra Petrovic, MD
NCT01512888

SCID-X1 is a genetic disorder of blood cells caused by DNA changes in a gene that is required for the normal development of the human immune system. The purpose of this study is to determine if a new method, called lentiviral gene transfer, can be used to treat SCID-X1. This method involves transferring a normal copy of the common gamma chain gene into the participant's bone marrow stem cells. The investigators want to determine if the procedure is safe, whether it can be done according to the methods they have developed, and whether the procedure will provide a normal immune system for the patient. It is hoped that this type of gene transfer may offer a new way to treat children with SCID-X1 that do not have a brother or sister who can be used as a donor for stem cell transplantation.

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