Significant Survival Benefit Seen With Addition of Bemarituzumab to Chemotherapy in FGFR2b-Positive Gastric/GEJ Cancer

stomach cancer
Five Prime Therapeutics, Inc. announced topline data from the phase 2 FIGHT study comparing bemarituzumab and chemotherapy with chemotherapy alone.

Bemarituzumab was found to significantly improve progression-free survival (PFS) and overall survival (OS) when added to frontline chemotherapy for patients with fibroblast growth factor receptor 2b (FGFR2b)-positive locally advanced or metastatic gastric and gastroesophageal junction (GEJ) cancer, according to topline data from the phase 2 FIGHT study.

All 3 of FIGHT’s ( Identifier: NCT03694522) efficacy end points — PFS, OS, and overall response rate (ORR) — achieved prespecified statistical significance at a 2-sided alpha of 0.20. Regarding PFS, the combination of bemarituzumab and modified leucovorin calcium, 5-fluorouracil, and oxaliplatin (mFOLFOX) led to a median PFS of 9.5 months vs 7.4 months with chemotherapy alone (HR, 0.68; 95% CI, 0.44-1.04; P =.073).

The median OS was 12.9 months with chemotherapy and had not yet been reached with the bemarituzumab-containing regimen (HR, 0.58; 95% CI, 0.35-0.95; P =.027). Adding bemarituzumab, a first-in-class targeted therapy, to chemotherapy correlated with a 13.1% improvement in ORR (P =.106).

Safety data showed that the incidence of all-grade (100.0% vs 98.7%) and serious toxicities (31.6% vs 36.4%) were comparable between the experimental and control arms. Toxicities that resulted in death occurred in 6.6% and 5.2% of patients who received the doublet therapy or chemotherapy only, respectively. Grade 3 or higher adverse events were observed to present at a higher frequency in the bemarituzumab plus modified FOLFOX arm (82.9% vs 74.0%).

The FIGHT trial enrolled 155 patients with histologically confirmed gastric or GEJ adenocarcinoma that was not amenable to curative treatment and FGFR2b overexpression. In the oncology space, FGFR2b, which is overexpressed in approximately 30% of HER2-positive gastric cancers worldwide, is regarded as a novel target not only in gastric and GEJ cancer, but also in squamous non–small cell lung cancer, triple-negative breast cancer, ovarian cancer, pancreatic cancer, and intrahepatic cholangiocarcinoma.

“We have known for some time that FGFR is a viable target in gastric cancer and many other malignancies. This is the first data to signal that a targeted therapy directed [at] FGFR2b may reduce the risk of disease progression and improve overall survival in gastric cancer,” said Zev A. Wainberg, MD, co-director of the Gastrointestinal Oncology Program and director of Early Phase Clinical Research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.


Five Prime announces bemarituzumab plus chemotherapy demonstrates significant progression-free and overall survival benefit compared to placebo plus chemotherapy in front-line advanced gastric and gastroesophageal junction cancer. News release. November 10, 2020. Accessed November 12, 2020.