First-In-Class Targeted Therapy Shows Survival Benefit Advanced Gastric/GEJ Adenocarcinoma Subset

Three efficacy end points, including progression-free survival (PFS), overall survival (OS), and overall response rate (ORR), met pre-specified statistical significance in the phase 2 FIGHT study (NCT03694522) of bemarituzumab (FPA144) in combination with modified FOLFOX6 (mFOLFOX6) as treatment of patients with FGFR2b-positive non-HER2-positive frontline advanced gastric or gastroesophageal junction (GEJ) cancer, Five Prime Therapeutics, Inc., announced in a press release.

The median PFS with the combination was 9.5 months with the combination versus 7.4 months with placebo (HR, 0.68; 95% CI, 0.44-1.04; P =.073), and the median OS was not reached with bemarituzumab treatment versus 12.9 months (HR, 95% CI, 0.35-0.95; P =.027). The ORR with the first-in-class FGFR2b-targeting antibody was improved by 13.1% (P =.106) in FIGHT.

“We have known for some time that FGFR is a viable target in gastric cancer and many other malignancies,” said Zev A. Wainberg, MD, associate professor of Medicine at University of California Los Angeles, co-director of the Gastrointestinal Oncology Program, and director of Early Phase Clinical Research at the Jonsson Comprehensive Cancer Center, in a statement. “This is the first data to signal that a targeted therapy directed to FGFR2b may reduce the risk of disease progression and improve overall survival in gastric cancer. This study result showing bemarituzumab’s potential benefit is an important and exciting development.”

The incidence of any grade adverse events (AEs) was comparable between the 2 arms, occurring in 100% in the combination arm and 98.7% in the control arm, and the incidence of serious AEs was also comparable (31.6% vs 36.4%, respectively). Deaths due to AEs occurred in 6.6% of the experimental arm versus 5.2% in the control arm.

Grade 3 or higher AEs were reported in 82.9% of the combination arm versus 74.0% with placebo. Corneal and stomatitis AEs were observed more frequently with the combination, and more patients discontinued treatment in the experimental arm as well (34.2%) compared with placebo (5.2%). Retinal detachment or hyperphosphatemia AEs were not reported in the bemarituzumab arm.

Although discontinuation was more common in the experimental arm, the efficacy end points all favored bemarituzumab.

“These results bring us one step closer to the first potential targeted therapy for advanced gastric cancer in over a decade,” said Helen Collins, MD, executive vice president and chief medical officer, Five Prime Therapeutics, in a statement. “Benefit was observed in patients whose tumors overexpressed FGFR2b, even without evidence of amplification, and that may broaden the therapeutic potential of bemarituzumab in more cancer types. We are excited about the results of the FIGHT trial and the opportunity to advance the development of bemarituzumab, the first and only investigational treatment targeting FGFR2b+. Five Prime is grateful to the patients and investigators who participated in our clinical trials, and we look forward to discussing next steps with health authorities worldwide.”

About 30% of patients with HER2-negative gastric cancers harbor an FGFR2b alteration in the tumor. FGFR2b is also overexpressed in a number of other cancers, including squamous non–small cell lung cancer, triple-negative breast cancer, ovarian cancer, pancreatic cancer, and intrahepatic cholangiocarcinoma.

FIGHT is a global randomized double-blind controlled study that is exploring the efficacy of bemarituzumab in combination with mFOLFOX6 compared with placebo and mFOLFOX6. To be included in the study, patients had to have gastric/GEJ adenocarcinoma not amenable to curative therapy, and ECOG performance status of 0 or 1, and adequate hematological, liver, and kidney function. They also had to have overexpression of FGFR2b and be eligible for mFOLFOX6.

The trial is still active but is no longer recruiting. Further results from this study will be presented at an upcoming medical meeting after the company completes a full evaluation of the FIGHT data.

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_{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. Give Prime Therapeutics, Inc. November 10, 2020. Accessed November 11, 2020. https://bit.ly/2UhZFLJ}