130MO - EDGE-Gastric Arm A1: Phase II study of domvanalimab (D), zimberelimab (Z), and FOLFOX in first-line (1L) advanced gastroesophageal (GE) cancer

Background

Adding programmed cell death protein 1 (PD-1) inhibitors to chemotherapy confers a survival advantage in 1L GE cancers, yet long-term outcomes remain poor. Dual PD-1 and anti-T-cell immunoglobulin and ITM domain (TIGIT) blockade increases tumor specific CD8+ T cells, resulting in potent antitumor activity. EDGE-Gastric Arm A1 (NCT05329766) evaluated safety/efficacy of the anti-TIGIT Fc-silent monoclonal antibody (mAb) D and the anti-PD-1 mAb Z in patients (pts) with 1L locally advanced unresectable/metastatic gastric/GE junction/E adenocarcinoma.

Methods

Pts received D 1600 mg intravenously (IV) every 4 weeks (Q4W) + Z 480 mg IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus + 2400 mg/m2 continuous 46-48-hour IV infusion) Q2W. Primary endpoints were safety and objective response rate (ORR) per RECIST 1.1. Secondary endpoints included ORR by PD-L1 status and PFS.

Results

As of data cutoff (12Mar2024), 41 pts were enrolled. There was an even distribution of pts from Asia vs. rest of world; 63% had gastric cancer. Median (m) time on treatment was 11.4 months, 13 pts (32%) continue on therapy. Confirmed ORR was 59% (95% CI 42, 74) and mPFS was 12.9 months (9.8, 13.8). Outcomes by PD-L1 status are in the table. Most common treatment-emergent adverse events (TEAE) were neutropenia (61%), nausea (59%), and anemia (29%). Infusion related reactions (investigator assessed) were observed in 20% (n=8); n=2 related to D/Z. Grade ≥3 TEAEs occurred in 73% of pts; 59% and 15% related to FOLFOX and D/Z, respectively. Serious TEAEs occurred in 37% of pts: 5% related to FOLFOX and none to D/Z. TEAEs leading to FOLFOX discontinuation occurred in 26 pts (63%), and D/Z discontinuation in 4 pts (10%). There were no treatment related deaths Table: 130MO

Tumor samples from 40 pts were available for central PD-L1 testing; NE: not estimable; PFS: progression free survival; TAP: Tumor Area Positivity.

Conclusions

Addition of DZ to FOLFOX showed encouraging ORR and mPFS, particularly in pts with PD-L1-high tumors. The regimen was well tolerated, with a similar AE profile to anti-PD-1+FOLFOX.

Clinical trial identification

NCT05329766.

Editorial acknowledgement

Medical writing assistance was provided by Emily Chastain, PhD of Arcus Biosciences, Inc.

Legal entity responsible for the study

Arcus Biosciences, Inc. and Gilead.

Funding

Arcus Bioscience, Inc. and Gilead.

Disclosure

S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: MSD, Daiichi Sankyo; Financial Interests, Personal, Steering Committee Member: Amgen; Financial Interests, Institutional, Funding: MSD, Lilly; Financial Interests, Institutional, Research Grant: BMS, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Indivumed, AstraZeneca; Financial Interests, Personal, Other, Durg supply for clinical trial: Merck; Financial Interests, Institutional, Coordinating PI, Drug supply for clincal trial: MSD; Financial Interests, Institutional, Local PI, drug supply for clinical trial: Zymeworks; Financial Interests, Institutional, Local PI, drug supply for clincial trial: Beigine; Financial Interests, Personal, Local PI: Roche. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono , Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD, LG Chem, Astellas, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, Idience, Alligator Bioscience AB; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. M. Pelster: Financial Interests, Institutional, Other, Consulting: AstraZeneca, CytomX, Daiichi Sankyo, Ipsen, Pfizer, Seagen, Arcus Biosciences, Elevation Oncology, EMD Serono, Jazz Pharmaceuticals, Stemline Therapeutics; Financial Interests, Institutional, Local PI: Agenus, Arcus Biosciences, Astellas, BeiGene, BioNTech, Bristol Myers Squibb, Codiak Biosciences, Eisai, Gilead, HiberCell, Immune-Onc Therapeutics, Leap Therapeutics, Novartis, OncXerna Therapeutics, Panbela Therapeutics, Revolution Medicines, Surface Oncology, SQZ Biotechnologies, Translational Genomics, TransThera Sciences, ZielBio, 1200 Pharma, Actuate Therapeutics, Compass Therapeutics, CytomX, Elevation Oncology, Exelixis, Impact Therapeutics, Tachyon Therapeutics, AbbVie, Affini-T Therapeutics, Elicio, Fate Therapeutics, Fog Pharmaceuticals, GSK, Jazz Pharmaceuticals, Kura Oncology, Neogene, Roche, SeaGen, Takeda. Z.A. Wainberg: Financial Interests, Personal, Advisory Board: Amgen, Astellas, Arcus, Bayer, AstraZeneca, Novartis, Roche, Ipsen, Daiichi, Merck, BMS, Merus; Financial Interests, Personal, Other, DMC: Pfizer; Financial Interests, Institutional, Steering Committee Member: Novartis, AstraZeneca; Financial Interests, Institutional, Coordinating PI: Ipsen; Financial Interests, Institutional, Local PI: Merck; Financial Interests, Institutional, Research Grant: BMS, Arcus. A. Sison, J. Scott, S. Nelson, D. Wishengrad, D.S.A. Nuyten: Financial Interests, Personal, Full or part-time Employment: Arcus Biosiences; Financial Interests, Personal, Stocks/Shares: Arcus Biosiences. J. Rhee: Financial Interests, Personal, Full or part-time Employment: Gilead; Financial Interests, Personal, Stocks/Shares: Gilead. Y.Y. Janjigian: Financial Interests, Personal, Advisory Board: AbbVie, Arcus Biosciences, Ask- Gene Pharma, Inc., AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Inc., Eli Lilly, GSK, Guardant Health, Inc., Imugene, Lynx Health, Merck, Sanofi Genzyme, Seagen, Zymeworks Inc.; Financial Interests, Personal, Other, Consulting: Amerisource Bergen, Astellas, Basilea Pharmaceutica, Geneos Therapeutics, Imedex, Inspirna, Mersana Therapeutics, Paradigm Medical Communications, Pfizer, Silverback Therapeutics; Financial Interests, Personal, Other, Consulting and Invited Speaker: Arcus Biosciences, AstraZeneca, Clinical Care Options, HMP Education, Merck Serono, PeerView Institue, Research to Practice; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Ed MedResources (OncInfo), H.C. Wainwright & Co., LLC, Merck, TotalCME, Talem Health; Financial Interests, Personal, Other, Consulting, Invited Speaker and Chair of Giants of Cancer Care Steering Committee: Michael J. Hennessy Associates; Financial Interests, Personal, Other, Consulting and Moderator: Physicians' Education Resource, LLC; Financial Interests, Personal, Stocks/Shares, Stock option: Inspirna; Financial Interests, Personal and Institutional, Research Grant: NCI, Department of Defense, Cycle for Survival, Fred's Team, Inspirna, Bayer, Genetech/Roche, Bristol Myers Squibb, Eli Lilly, Merck, Transcenta, Stand Up To Cancer, AstraZeneca, Arcus Biosciences, Astellas; Financial Interests, Personal, Steering Committee Member: AstraZeneca, Transcenta Holding Limited.