146P - Phase (ph) Ib results of bemarituzumab (BEMA) added to capecitabine/oxaliplatin (CAPOX) or S-1/oxaliplatin (SOX) with or without nivolumab (NIVO) for previously untreated advanced gastric/gastroesophageal junction cancer (G/GEJC): FORTITUDE-103 study

Background

In the ph2 FIGHT trial, BEMA+mFOLFOX6 had promising efficacy in patients with FGFR2b-overexpressed (FGFR2b+) advanced G/GEJC. FORTITUDE-103 explores a Q3W dosing schedule of first-line BEMA in combination with other oral anticancer therapies among patients (pts) in South Korea, Taiwan, Singapore, and Japan (interim analysis, data cutoff 2 May 2023).

Methods

BEMA-dose level 1 (DL1) (15mg/kg Q3W with 1 additional 7.5mg/kg only on C1D8)+CAPOX was assessed in cohort A-DL1. After BEMA-DL1 was found to have an acceptable safety/tolerability profile, BEMA-DL2 (22mg/kg Q3W with 1 additional 11mg/kg only on C1D8) was initiated in newly-enrolled pts as cohort A-DL2, C, and D. Cohorts C and D received BEMA-DL2, NIVO, and CAPOX (C) or SOX (D).

Results

24 pts were enrolled (17 m/7 f, mean age 60.3 y) as follows: BEMA-DL1+CAPOX (A-DL1; N=6), BEMA-DL2 +CAPOX (A-DL2; n=4), BEMA-DL2 +CAPOX+NIVO [C; n=7], BEMA-DL2+SOX+NIVO [D; n=7]. BEMA-DL1+CAPOX was found to have a favorable safety profile. No dose-limiting toxicities were reported across cohorts A-DL1, A-DL2, C, and D; no new safety signals were identified. Median (min-max) BEMA treatment duration was 16.0 wk (3.0-35.9). 6 pts (25.0%) had 8 serious AEs (including 1 pt with AE assessed by PI as BEMA-related); 14 pts (58.3%) had 24 grade ≥3 AEs (including 7 pts with AE assessed by PI as BEMA-related). 5 pts (20.8%) reported one or more grade ≥2 ocular AE. 2 pts in cohort A-DL1 discontinued BEMA for ocular-related non-serious AEs considered related to BEMA (visual acuity reduced [n=2] and corneal opacity [n=1]); both pts recovered. 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. Updated data will be presented at the congress.

Conclusions

This analysis suggest that bemarituzumab Q3W dosing in combination with CAPOX or SOX (with or without NIVO) has an acceptable safety profile.

Clinical trial identification

NCT05322577.

Editorial acknowledgement

Medical writing support was provided by Tim Peoples, MA, ELS, contractor to Amgen Inc.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

K. Lee: Financial Interests, Personal, Advisory Board: BMS (Korea), Bayer (Korea), Daiichi Sankyo (Korea), Merck Sharp & Dohme (Korea), Metafines, Vifor pharma (Korea), Astellas (Korea); Financial Interests, Personal, Invited Speaker: Boryung Co.; Financial Interests, Institutional, Local PI: ABLBIO, ALX Oncology, Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, BeiGene, Bolt therapeutics, Daiichi Sankyo, Exelixis, Genexine, Green Cross Corp, InventisBio, LSK BioPharma, Leap therapeutics, Macrogenics, MedPacto, Merck KGaA, Merck Sharp & Dohme, Oncologie, Ono pharmaceutical, Pfizer, Pharmacyclics, Seagen, Taiho Pharmaceutical, Trishula therapeutics, Y-BIOLOGICS, Zymeworks,; Non-Financial Interests, Personal, Leadership Role, SMC chair of ASPEN-06 study: ALX Oncology. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, Liscure. H. Hirano: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Ono Pharmaceutical, Teijin Phama, Novartis; Financial Interests, Personal, Writing Engagement: Nichi-Iko; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Ono Pharmaceutical, Janssen Pharmaceutical, Merck Biopharma, Bristol Myers Squibb, Pfizer, Eisai, Amgen, Astellas, Seagen, MSD, Insyte, BeiGene, Novartis. Y. Sunakawa: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Bristol-Byers Squibbb, Chugai Pharmaceutical, Takeda, Taiho Pharmaceutical, Merck Biopharma, Daiichi Sankyo, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Merck Biopharma; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda, Otsuka Pharm, Parexel International Inc., IQVIA, Ono Pharmaceutical, CMIC Shift Zero K.K., PRA health sciences, Inc., Amgen; Non-Financial Interests, Personal, Project Lead: Japan Clinical Cancer Research Organization. C. Lin: Financial Interests, Personal, Other, Travel support: BeiGene, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo, Novartis, AbbVie, PharmaEngine, Merck KGaA, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Roche; Financial Interests, Personal, Other, Travel Support: IMPACT Therapeutics. W.P. Yong: Financial Interests, Personal, Invited Speaker: DKSH Singapore Pte Ltd, AstraZeneca Singapore Pte Ltd, Bristol Myers Squibb (S) Pte Ltd, MSD Pharma (Singapore) Pte Ltd, Novartis (S) Pte Ltd; Financial Interests, Personal, Advisory Board: Ipsen Pharma Singapore Pte Ltd, Amgen; Financial Interests, Institutional, Local PI: Novartis (S) Pte Ltd, Amgen. T. Kawakami: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, honoraria: Bristol Myers Squibb, Ono Pharmaceutical, Yakult Honsha, Daiichi Sankyo. T. Oshima: Financial Interests, Personal, Invited Speaker: Taiho, Astellas; Financial Interests, Personal, Writing Engagement: Astellas; Financial Interests, Personal, Other, research grant: Taiho, Kyowa Kirin, Chugai, Nihon kayaku. Z. Li: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. M. Hopkins: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. A. Levin: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. H. Wang: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. L. Goldstein: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. D. Zhou: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas; Financial Interests, Personal, Invited Speaker: MSD, Lilly, 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, Coordinating PI, Drug supply for clnical trial: Incyte. All other authors have declared no conflicts of interest.