1386P - Phase II study of bavituximab (bavi), a first-in-class antibody targeting phosphatidylserine (PS), plus pembrolizumab (pembro) in advanced gastric or gastroesophageal junction (GEJ) cancer

Background

Bavi, a monoclonal antibody designed to inhibit the immunosuppressive effects of PS through interaction with TIM andTAM receptor family members in the tumor microenvironment (TME), is being evaluated in combination with pembro in patients with advanced gastric and GEJ cancer.

Methods

ONCG100 is a phase II, multicenter, open-label, two-cohort global study designed to assess the safety, tolerability, and antitumor activity of bavi (3 mg/kg, QW) in combination with pembro (200 mg, Q3W) in patients with advanced gastric or GEJ cancer regardless of programed death-ligand 1 (PD-L1) status who have progressed on ≥1 prior standard therapy (NCT04099641). Patients were either naïve to checkpoint inhibitors (CPIs, Group 1) or previously relapsed on a CPI (Group 2); if known, MSI-H patients were excluded. Pre-treatment biopsies were required for pre-specified biomarker analysis using the Xerna™ TME Panel.

Results

A total of 75 patients have been enrolled (Group 1 n=61, Group 2 = 14). The most frequent grade 3 TEAEs were anemia (14%), ascites and increased aspartate aminotransferase (6%). There were no related grade 4 or grade 5 TEAEs. Antitumor activity for Group 1 is summarized in the Table. Table: 1386P

Anti-tumor activity in CPI naïve patients ¹

¹ Includes MSS status unknown.

Conclusions

The combination of bavi + pembro is well tolerated and active in gastric cancer, including in patient with CPS<1, a group less responsive to CPI. In addition, the Xerna™ TME Panel was likely predictive of treatment response. Retrospective analysis suggests baseline NLR may have a prognostic or predictive role. The anti-tumor activity of bavi + pembro across high and low CPS suggests that bavi sensitizes cancers to CPI activity, potentially expanding the use of the combination to patients typically less responsive to CPIs, and warrants confirmation.

Clinical trial identification

NCT04099641.

Editorial acknowledgement

Legal entity responsible for the study

OncXerna Therapeutics.

Funding

OncXerna Therapeutics.

Disclosure

I. Chau: Financial Interests, Personal, Advisory Board: Astella; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Boehinger Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eli-Lilly; Financial Interests, Personal, Invited Speaker: Eli-Lilly; Financial Interests, Personal, Other, DMC chairman: Five Prime Therapeutics; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Merck-Serono; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: OncXerna Therapeutics; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Other, Coordinating PI: Cilag-Janssen; Financial Interests, Institutional, Other, Coordinating PI: Eli-Lilly. K. Culm-Merdek: Financial Interests, Personal, Stocks/Shares: OncXerna Therapeutics; Financial Interests, Personal, Stocks/Shares: BMS. J.C. Bendell: Financial Interests, Institutional, Advisory Role: Amgen; Financial Interests, Institutional, Advisory Role: Apexigen; Financial Interests, Institutional, Advisory Role: Arch Oncology; Financial Interests, Institutional, Advisory Role: ARMO BioSciences; Financial Interests, Institutional, Advisory Role: Array BioPharma; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Bayer; Financial Interests, Institutional, Advisory Role: Beigene; Financial Interests, Institutional, Advisory Role: Bicycle Therapeutics; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Role: Celgene; Financial Interests, Institutional, Advisory Role: Cerulean Pharma; Financial Interests, Institutional, Advisory Role: Continuum Clinical; Financial Interests, Institutional, Advisory Role: Cyteir; Financial Interests, Institutional, Advisory Role: Daiichi Sankyo; Financial Interests, Institutional, Advisory Role: EMD Serono; Financial Interests, Institutional, Advisory Role: Evelo Therapeutics; Financial Interests, Institutional, Advisory Role: Five Prime Therapeutics; Financial Interests, Institutional, Advisory Role: FORMA Therapeutics; Financial Interests, Institutional, Advisory Role: Fusion Pharmaceuticals; Financial Interests, Institutional, Advisory Role: Genentech/Roche; Financial Interests, Institutional, Advisory Role: Gilead Sciences; Financial Interests, Institutional, Advisory Role: GlaxoSmithKline; Financial Interests, Institutional, Advisory Role: Incyte; Financial Interests, Institutional, Advisory Role: Innate Pharma; Financial Interests, Institutional, Advisory Role: Ispen; Financial Interests, Institutional, Advisory Role: Janssen; Financial Interests, Institutional, Advisory Role: Kyn Therapeutics; Financial Interests, Institutional, Advisory Role: Leap Therapeutics; Financial Interests, Institutional, Advisory Role: Lilly; 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Financial Interests, Institutional, Funding, Research: Zymeworks; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: ARMO BioSciences; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: Boehringer Ingeheim; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: Celgene; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: Daiichi Sankyo; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: FORMA Therapeutics; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: Gilead Sciences; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: Ispen; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: Lilly; 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D.V. Catenacci: Financial Interests, Institutional, Other, Honoraria: Amgen; Financial Interests, Institutional, Other, Honoraria: Astellas Pharma; Financial Interests, Institutional, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Honoraria: Five Prime Therapeutics; Financial Interests, Institutional, Other, Honoraria: Foundation Medicine; Financial Interests, Institutional, Other, Honoraria: Genentech/Roche; Financial Interests, Institutional, Other, Honoraria: Gritstone Oncology; Financial Interests, Institutional, Other, Honoraria: Guardant Health; Financial Interests, Institutional, Other, Honoraria: Lilly; Financial Interests, Institutional, Other, Honoraria: Merck; Financial Interests, Institutional, Other, Honoraria: Seattle Genetics; Financial Interests, Institutional, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Institutional, Other, Honoraria: Tempus; Financial Interests, Institutional, Advisory Role: Amgen; Financial Interests, Institutional, Advisory Role: Astellas Pharma; Financial Interests, Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Role: Genentech/Roche; Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: Merck; Financial Interests, Institutional, Advisory Role: Seattle Genetics; Financial Interests, Institutional, Advisory Role: Taiho Pharmaceutical; Financial Interests, Institutional, Speaker’s Bureau: Foundation Medicine; Financial Interests, Institutional, Speaker’s Bureau: Genentech; Financial Interests, Institutional, Speaker’s Bureau: Guardant Health; Financial Interests, Institutional, Speaker’s Bureau: Lilly; Financial Interests, Institutional, Speaker’s Bureau: Merck; Financial Interests, Institutional, Speaker’s Bureau: Tempus. J. Lee: Financial Interests, Personal, Advisory Board: Mirati; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: OncXerna Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca. M.F. Chaney: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc; Other, Personal, Member: ASCO; Other, Personal, Member: AACR; Other, Personal, Member: SITC. S. MacIntyre: Financial Interests, Personal, Full or part-time Employment: OncXerna Therapeutics; Financial Interests, Personal, Stocks/Shares: OncXerna Therapeutics; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. S. Gopal: Financial Interests, Personal, Full or part-time Employment: OncXerna Therapeutics. V. Chamberlain Santos: Financial Interests, Personal, Full or part-time Employment: OncXerna Therapeutics. H. Youssoufian: Financial Interests, Personal, Full or part-time Employment: OncXerna Therapeutics. C. Mockbee: Financial Interests, Personal, Full or part-time Employment: OncXerna Therapeutics; Financial Interests, Personal, Stocks/Shares: OncXerna Therapeutics. L. Benjamin: Financial Interests, Personal, Full or part-time Employment, CEO, founder: OncXerna Therapeutics; Financial Interests, Personal, Stocks/Shares: OncXerna Therapeutics. H. Park: Financial Interests, Institutional, Principal Investigator, Local: Ambrx; Financial Interests, Institutional, Principal Investigator, Local: Amgen; Financial Interests, Institutional, Principal Investigator, Local: Aprea Therapeutics AB; Financial Interests, Institutional, Principal Investigator, Local: Array BioPharma; Financial Interests, Institutional, Principal Investigator, Local: Bayer; Financial Interests, Institutional, Principal Investigator, Local: BeiGene; Financial Interests, Institutional, Principal Investigator, Local: BJ Bioscience; Financial Interests, Institutional, Principal Investigator, Local: Bristol-Myers Squibb; Financial Interests, Institutional, Principal Investigator, Local: Daiichi Pharmaceutical; Financial Interests, Institutional, Principal Investigator, Local: Eli Lilly; Financial Interests, Institutional, Principal Investigator, Local: Elicio Therapeutics; Financial Interests, Institutional, Principal Investigator, Local: EMD Serono; Financial Interests, Institutional, Principal Investigator, Local: Genentech; Financial Interests, Institutional, Principal Investigator, Local: Gilead Sciences; Financial Interests, Institutional, Principal Investigator, Local: GlaxoSmithKline; Financial Interests, Institutional, Principal Investigator, Local: Gossamer Bio; Financial Interests, Institutional, Principal Investigator, Local: Hoffman-LaRoche; Financial Interests, Institutional, Principal Investigator, Local: Hutchison MediPharma; Financial Interests, Institutional, Principal Investigator, Local: ImmuneOncia Therapeutics; Financial Interests, Institutional, Principal Investigator, Local: Incyte; Financial Interests, Institutional, Principal Investigator, Local: Jounce Therapeutics; Financial Interests, Institutional, Principal Investigator, Local: Mabspace Biosciences; Financial Interests, Institutional, Principal Investigator, Local: MacroGenics; Financial Interests, Institutional, Principal Investigator, Local: Medimmune; Financial Interests, Institutional, Principal Investigator, Local: Medivation; Financial Interests, Institutional, Principal Investigator, Local: MERCK; Financial Interests, Institutional, Principal Investigator, Local: Millennium; Financial Interests, Institutional, Principal Investigator, Local: Mirati Therapeutics; Financial Interests, Institutional, Principal Investigator, Local: Novartis Pharmaceuticals; Financial Interests, Institutional, Principal Investigator, Local: OncXerna Therapeutics; Financial Interests, Institutional, Principal Investigator, Local: Pfizer; Financial Interests, Institutional, Principal Investigator, Local: PsiOxus Therapeutics; Financial Interests, Institutional, Principal Investigator, Local: Puma Biotechnology; Financial Interests, Institutional, Principal Investigator, Local: Regeneron Pharmaceuticals; Financial Interests, Institutional, Principal Investigator, Local: Seattle Genetics; Financial Interests, Institutional, Principal Investigator, Local: Synermore; Financial Interests, Institutional, Principal Investigator, Local: Taiho Pharmaceutical; Financial Interests, Institutional, Principal Investigator, Local: TopAlliance Biosciences; Financial Interests, Institutional, Principal Investigator, Local: Turning Point Therapeutics; Financial Interests, Institutional, Principal Investigator, Local: Vedanta Biosciences; Financial Interests, Institutional, Principal Investigator, Local: Vertex Pharmaceuticals; Financial Interests, Institutional, Principal Investigator, Local: Xencor Inc.