Bemarituzumab Plus Chemo Shows Promise in Front-Line Advanced Gastric & GEJ Cancer

The phase 2 FIGHT trial, whichcompared modified FOLFOX6 (mFOLFOX6; leucovorin calcium, fluorouracil, and oxaliplatin) chemotherapy in combination with bemarituzumab (bema, FPA144) in patients with FGFR2b-positive, HER2-negative front-line advanced gastric or gastroesophageal junction (GEJ) cancer, achieved pre-specified statistical significance across all 3 of its primary end points, according to Five Prime Therapeutics, the developer of the agent.

In the global, randomized, double-blind, placebo-controlled, progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) achieved pre-specified statistical significance at a 2-sided alpha of 0.20. Median PFS improved from 7.4 months to 9.5 months (HR, 0.68; 95% CI, 0.44-1.04; P = .073) and median OS improved from 12.9 months to not reached (HR, 0.58; 95% CI, 0.35-0.95; P = .027). ORR improved by 13.1% (P = .106).

“These results bring us one step closer to the first potential targeted therapy for advanced gastric cancer in over a decade,” Helen Collins, MD, executive vice president and chief medical officer at Five Prime, said in a press release. “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-positive],” added Collins. “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.”

The FGFR2b Inhibition in Gastric and Gastroesophageal Junction Cancer Treatment (FIGHT) trial (NCT03694522) was designed to evaluate the efficacy and safety of bemarituzumab in combination with mFOLFOX6 versus mFOLFOX6 plus placebo in the front-line setting of patients with newly diagnosed FGFR2b-positive, locally advanced or metastatic gastric and GEJ cancer.

Notably, patients’ tumors were deemed to be FGFR2b-positive by immunohistochemistry and by FGFR2 gene amplification using a blood-based circulating tumor DNA assay.

The trial enrolled a total of 155 patients in 15 countries across Asia, the EU, and the US.

Regarding safety, the incidence of all grade adverse events (AEs) was found to be similar in the treatment and control arms of the study (100% vs 98.7%, respectively), as were serious AEs (31.6% vs 36.4%) and deaths due to AEs (6.6% vs 5.2%). However, AEs of grade 3 or higher were reported more often in the treatment arm than in the placebo arm (82.9% vs 74.0%).

Moreover, corneal and stomatitis AEs were reported more frequently in the bemarituzumab arm, and more patients discontinued bemarituzumab (34.2%) due to an AE compared to placebo (5.2%). Importantly though, no AEs of retinal detachment or hyperphosphatemia were observed in the bemarituzumab arm.

Overall, Five Prime suggested that the phase 2 FIGHT trial results validate the importance of the novel target, FGFR2b, which is overexpressed in approximately 30% of HER2-negative gastric cancers worldwide. Further, the company indicated it will complete a full evaluation of the available FIGHT phase 2 data and work with investigators to share the results at an upcoming medical conference.

Reference:

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]. South San Francisco, California. Published November 10, 2020. Accessed November 11, 2020. https://investor.fiveprime.com/news-releases/news-release-details/five-prime-announces-bemarituzumab-plus-chemotherapy