Cho, May

TPS228 Background: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and the second leading cause of cancer-related mortality worldwide. PD-1/PD-L1 inhibition, in combination with other modalities, has demonstrated significant benefit in patients (pts) with microsatellite instability-high or mismatch repair–deficient CRC. However, these agents have limited, if any, clinical benefit in pts with microsatellite stable (MSS) or mismatch repair–proficient (pMMR) CRC. RP2 is an enhanced potency oncolytic herpes simplex virus type 1 which expresses the fusogenic gibbon ape leukemia virus glycoprotein with the R sequence deleted (GALV-GP-R–), granulocyte-macrophage colony-stimulating factor (GM-CSF), and an anti–CTLA-4 antibody-like molecule; RP3 additionally expresses 4-1BB and CD40 activating ligands but does not express GM-CSF. Both agents have demonstrated preliminary safety and antitumor activity in pts with solid tumors. This study will evaluate the safety and activity of RP2 and RP3 in combination with atezolizumab (Atezo) plus bevacizumab (Bev) in pts with advanced MSS/pMMR CRC (NCT05733611). Methods: Pts with a histologic diagnosis of unresectable and/or metastatic CRC, with documented MSS or pMMR status, and previously treated with up to 3 standard-of-care systemic regimens will be enrolled in the RP2 + Atezo + Bev or RP3 + Atezo + Bev treatment groups (30 pts per group). Further key inclusion criteria include Eastern Cooperative Oncology Group performance status 0 to 1 and adequate hepatic, renal, and hematologic function. RP2/RP3 will be injected into tumors by direct or image-guided injection. Pts will receive 8 total doses of up to 10 mL of RP2 or RP3, with a first dose concentration of 1 × 106 plaque-forming units (PFU)/mL, followed by 3 doses of 1 × 107 PFU/mL every 2 weeks, and then 4 doses of 1 × 107 PFU/mL every 3 weeks. Pts may receive a second course of up to 8 injections of RP2/RP3 if study criteria are met. Bev will be administered starting on week 1; Atezo will be administered starting week 7. The primary endpoint is objective response rate; secondary endpoints are safety, overall survival, progression-free survival, duration of response, and complete response rate. Antitumor activity will be evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 as modified for this study. Safety will be assessed by physical examination, clinical laboratory evaluations, vital signs, and monitoring for adverse events (AEs; including serious AEs). Clinical trial information: NCT05733611 .

e16200 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Indoleamine-2,3-dioxygenase (IDO) is an intracellular enzyme expressed by HCC which helps to orchestrate immune suppression within the tumor microenvironment (TME) and may contribute to primary and acquired resistance of PD-(L)1 inhibitors. BMS-986205 is a novel oral drug that potently and selectively inhibits IDO1. This Phase I/II study is evaluating the safety and tolerability of the combination of BMS-986205 and nivolumab as first-line therapy in HCC. Methods: Patients (pts) ≥18y with untreated, unresectable/metastatic HCC received BMS-986205 in combination with nivolumab. A fixed dose of Nivolumab 240mg/m2 IV was administered on Day 1 of each 14-day cycle. BMS-986205 was an oral tablet administered daily; a total of two dose levels (50-100mg) were given to determine dose limiting toxicities (DLT) during the dose-escalation Phase I of the study. Safety was assessed using CTCAE v5.0 criteria, and efficacy was assessed by objective response rate (ORR) using RECIST v1.1 criteria. Secondary objectives included preliminary data on disease control rate (DCR), duration of response (DOR), ORR using immune RECIST criteria (iRECIST), progression free survival (PFS) and overall survival (OS). Results: Here we report the results of the dose escalation cohort. Eight pts were treated with median age 69y [60-76]; 75% male; and PS 0 (3 pts) or 1 (5 pts). Pts were White (62.5%), Asian (25%), and African American (12.5%). Six of 8 pts had underlying viral hepatitis (5 hepatitis C, 1 hepatitis B), and all pts were Child Pugh A at enrollment with median baseline alpha-fetoprotein (AFP) level 41.8 [3.8–917.2]; 4 pts received prior local therapies. A total of 91 cycles of therapy were administered; 2 pts received 27 and 43 cycles of treatment each. Six pts were evaluable for DLT; 2 pts were replaced for DLT assessment due to insufficient dose administered, unrelated to toxicity. No DLTs were observed at either the 50 or 100mg dose of BMS-986205. There were 24 treatment-related adverse events (TRAEs), 4 of which were Grade 3 events; there were no Grade 4-5 events. The most common TRAEs of all grades were AST elevation and ALT elevation in 3 pts, and diarrhea, maculopapular rash and increased alkaline phosphatase in 2 pts each. Grade 3 events were diarrhea and AST elevation (1 pt), and hyperglycemia and pancreatitis requiring treatment discontinuation (1 pt). Eight pts were evaluable for efficacy with best response of partial response in 1 pt (12.5%) and stable disease in 3 pts (37.5%), yielding a DCR of 50%. Median PFS was 8.5 weeks; median OS has not been reached. Conclusions: Combination BMS-986205 and nivolumab showed a manageable safety profile with durable benefit as 1st line therapy in a meaningful subset of patients with unresectable/metastatic HCC. Clinical trial information: NCT03695250.

Cholangiocarcinoma (CCA) is a heterogenous group of malignancies originating in the biliary tree, and associated with poor prognosis. Until recently, treatment options have been limited to surgical resection, liver-directed therapies, and chemotherapy. Identification of actionable genomic alterations with biomarker testing has revolutionized the treatment paradigm for these patients. However, several challenges exist to the seamless adoption of precision medicine in patients with CCA, relating to a lack of awareness of the importance of biomarker testing, hurdles in tissue acquisition, and ineffective collaboration among the multidisciplinary team (MDT). To identify gaps in standard practices and define best practices, multidisciplinary hepatobiliary teams from the University of California (UC) Davis and UC Irvine were convened; discussions of the meeting, including optimal approaches to tissue acquisition for diagnosis and biomarker testing, communication among academic and community healthcare teams, and physician education regarding biomarker testing, are summarized in this review.

e18521 Background: About 40% of the US population are from minority groups. Minority pts are under-represented in oncology clinical trials, which limits the applicability of results to the general population and perpetuates poor relationships between healthcare systems and minority communities. This assessment investigated underlying causes of this lack of minority representation in clinical trials and proposes plans to promote diversity. Methods: To better understand the limited inclusion of under-represented pts in oncology clinical trials, 10 specialists in cancer care were selected to provide their perspectives. Specialists were chosen because of their experience enrolling minority pts in clinical trials and met virtually in Dec 2020 via Within3, a secure digital communication platform, to discuss obstacles faced in recruiting minority pts and potential strategies to address these concerns. Specificity and alignment in responses were achieved through software analytics and follow-up queries. Results: The 10 specialists identified as Asian (10%), Black (30%), White (50%), and Hispanic (10%), and began practicing medicine in the 1980s-2010s. All are involved in clinical research and treat a range of minority pts in both urban and suburban settings. Most specialists (8/10) reported treating > 20 minority pts with cancer annually. However, few specialists (2/10) reported that > 20% of their minority pts have enrolled in clinical trials. Specialists agreed that minority pts experience barriers to participation in clinical research, including lack of trust in the healthcare system, materials in their native languages, financial support, minority investigators involved in clinical trials, and accessible study sites. The specialists proposed strategies that could be implemented to increase minority enrollment. These included study sites where minority populations live and industry funded outreach and educational efforts in minority communities. If sites are more accessible, this can reduce time and financial pressures associated with study participation. The specialists recommended that studies be designed to be more supportive of minority populations, specifically regarding inclusion and exclusion criteria and reimbursement of costs. They also advised that increased diversity among clinical researchers and allied personnel may increase the ability of the clinical team to connect with pts and assist in building trust in their communities. Finally, they emphasized the importance of providing informed consent forms and study materials in pts’ native languages. Conclusions: While challenges exist to increasing diversity in oncology clinical studies, a broad consortium of clinical specialists agreed that they can be addressed by community outreach and education, making study sites more accessible, availability of study materials in pts’ native languages, and improving diversity of clinical teams.