1526P - Phase Ib results of bemarituzumab (BEMA)+mfolfox6+nivolumab (NIVO) for advanced gastric/gastroesophageal junction cancer (G/GEJC): Fortitude-102 part 1

Background

In the phase (ph) 2 FIGHT trial, BEMA+mFOLFOX6 had promising efficacy in patients with FGFR2b-selected G/GEJC. FORTITUDE-102 comprises part 1 (open-label ph1b) evaluated the safety and tolerability of BEMA+mFOLFOX6+NIVO and part 2 (randomized ph3) the safety and efficacy compared with placebo. Here, we present the results of part 1.

Methods

Up to 20 patients (pts) with/without FGFR2b overexpression could be enrolled. The initial dose of BEMA was 15 mg/kg IV Q2W with one 7.5 mg/kg dose on cycle 1 day 8. The dose-limiting toxicity (DLT) period was 28 days. At least 6 pts were treated at a dose level with less than 33% incidence of DLTs to determine the recommended ph3 dose (RP3D). An ad hoc review was performed 6mo after the DLT period.

Results

Eight pts (50-71 y) were enrolled and evaluated for DLTs: 6 pts were men, 4 pts were Asian, and 4 pts were White. No DLTs were reported; no new safety signals were identified. Mean exposures for the first 3 cycles and estimated terminal elimination half-life (7-11 days) were consistent with historical data. No meaningful BEMA exposure changes were observed with the addition of NIVO, indicating no drug interactions. The RP3D was 15 mg/kg Q2W with one 7.5mg/kg dose on cycle 1 day 8. Six mo post-DLT period, the median treatment duration was ∼34 weeks (8-40). Four pts had 6 serious AEs (n=1 AE [hyponatremia] considered BEMA-related); 7 pts had 13 grade ≥3 AEs (n=4 [neutropenia, mucositis, hyponatremia, and delirium] in 2pts considered BEMA-related). Five pts reported 8 ocular AEs of grades ≤2, with a median time to onset of ∼17 weeks. No AEs led to BEMA discontinuation. Treatment was interrupted in 4 pts due to BEMA-related AEs (1 was ocular related). PR was seen in 3 pts, SD in 4 pts, and PD in 1 pt. BEMA was stopped for consent withdrawal in 1pt and PD in 2pts. Updated data will be presented at the congress.

Conclusions

This is the first time a combination of BEMA, mFOLFOX6, and NIVO is assessed. In part 1, consistent safety and PK profiles suggest no negative interaction, with no new safety signals after 6 mo.

Clinical trial identification

NCT05111626.

Editorial acknowledgement

Sahishnu Patel of Amgen Inc provided medical writing support.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

Z.A. Wainberg: Financial Interests, Personal, Funding, Honoraria: Amgen, Arcus, AstraZeneca, Daiichi Sankyo, Bayer, BMS, Merck, Ipsen, Gilead, Arcus, Astellas, Seagen, Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor, Advisory/Consultancy: Amgen, Arcus, AstraZeneca, Daiichi Sankyo, Bayer, BMS, Merck, Ipsen, Novartis, Gilead, Arcus, Astellas, Seagen; Financial Interests, Institutional, Research Funding: Amgen, AstraZeneca, Daiichi Sankyo, Bayer, BMS, Merck, Ipsen, Five Prime, Gilead, Arcus, Astellas, Molecular Templates, Roche/Genentech, Array/Pfizer. K. Yamaguchi: Financial Interests, Personal, Invited Speaker: Taiho Pharm; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Bristol Myers Squibb, Ono, Eli Lilly Japan; Financial Interests, Institutional, Funding: Taiho. J.A. Ajani: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting: BMS, Merck, Astellas, Taiho, More, Zymeworks, BeiGene, Dava, AstraZeneca, Acrotech, Daiichi Sankyo, Vaccinogen, Innovent, Merck Serrono, Oncotherics, Bayer, OncLive, FivePrime, Amgen, GRAIL, Novartis, Geneos, Arcus, Servier, BI, Gilead. J. Chao: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Institutional, Research Funding: Astellas Pharma, Merck, and Eterna Therapeutics; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: Eli Lilly, Merck, AstraZeneca, Foundation Medicine, Daiichi Sankyo, MacroGenics, Amgen, Ono Pharmaceutical, Bristol Myers Squibb, Astellas Pharma, Turning Point Therapeutics, Silverback Therapeutics, Novartis, Coherus BioSciences, Geneos Therapeutics, Roc; Financial Interests, Personal, Advisory Board, Advisory board/DSMB: Yiviva. M. Moehler: Financial Interests, Personal, Advisory Board: BMS, Servier, Amgen, Lilly, BeiGene, Novartis, Taiho, Daiichi Sankyo, Amgen, MD; Financial Interests, Personal, Invited Speaker: MSD, BMS, Falk foundation, AIO, BeiGene, Amgen; Financial Interests, Institutional, Advisory Board: Bayer, Sanofi; Financial Interests, Personal, Other, Chair: EORTC. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, LISCure. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, ALX, Amgen, Array, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks; Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. P. Yen, Y. Motii, D. Zhou, T. Murias Dos Santos: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. K. Shitara: Financial Interests, Personal, Advisory Board: Lilly, Bristol Myers Squibb, Takeda, Pfizer, Ono Pharmaceutical, MSD, Taiho, Novartis, AbbVie, GSK, Daiichi Sankyo, Amgen, Boehringer Ingelheim, Guardant Health Japan Corp, Astellas; Financial Interests, Personal, Invited Speaker: Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Research Grant: Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho, Chugai Pharmaceutical, MSD, Eisai, Amgen.