Bemarituzumab, Chemotherapy Show Potential for Treatment of Gastric, Gastroesophageal Junction Cancers

Results from the phase 2 FIGHT trial presented at the 2021 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Virtual Symposium have shown both the importance of fibroblast growth factor receptor 2 (FGFR2b) overexpression as well as the potential of bemarituzumab plus chemotherapy in the frontline treatment for FGFR2b-positive gastric and gastroesophageal junction (GEJ) cancers.

The fibroblast growth factor (FGF) and FGFR pathway is implicated in the development and growth of cancer cells, according to a press release. FGFR2b is a splice form of FGFR found in tumors of epithelial origin. Data from the FIGHT trial suggests that approximately 30% of patients with non-human epidermal growth factor 2 (HER2)-positive GEJ cancers overexpress FGFR2b.

The FIGHT trial evaluated bemarituzumab plus chemotherapy compared to a placebo plus chemotherapy in patients with FGFR2b-positive, HER2-negative frontline advanced gastric or GEJ cancer. It enrolled 155 patients in 15 countries, with 77 patients randomized to the bemarituzumab arm and 78 patients to the placebo arm.

According to a Five Prime Therapeutics, a clinical stage biotechnology company, the phase 2 trial met all 3 efficacy endpoints and demonstrated statistically significant and clinically meaningful improvements in the primary endpoint of progression-free survival (PFS). It also demonstrated meaningful improvements in the secondary endpoints of overall survival (OS) and overall response rates (ORR).

Furthermore, additional analysis showed a positive correlation between benefit and the percentage of FGFR2b-positive tumor cells. The study authors said this finding confirms the importance of the FGFR2b target and the activity of bemarituzumab.

“Systemic chemotherapy is the standard of care for this deadly and aggressive form of gastric cancer,” said Zev A. Wainberg, MD, associate professor of medicine at the University of California, Los Angeles, in a prepared statement. “The FIGHT trial results demonstrate that treatment with bemarituzumab in combination with chemotherapy can deliver a significant reduction in the risk of disease progression and death in [patients with gastric cancer] whose tumors overexpress FGFR2b.”

The incidence of all grade adverse events was similar in both arms of the trial, with 100% in the bemarituzumab arm and 98.7% in the placebo arm. Corneal events were more frequent in the bemarituzumab arm (67.1% vs 10.4%), with the most common events being dry eye, keratitis, and punctate keratitis. Stomatitis and elevated transaminases were also more common in the bemarituzumab arm. Grade 3 and higher adverse events, serious adverse events, and deaths were comparable across arms.

The investigators noted that ocular events are common in therapies targeting FGFR, and more patients in the FIGHT trial discontinued bemarituzumab compared to placebo due to an adverse event (34.2% vs 5.2%) with the majority of those patients discontinuing due to an ocular event.

“The phase 2 FIGHT clinical trial results validate our pioneering work on the role of FGFR2b overexpression in gastric cancer, and we’re excited about the implications of this new scientific understanding for other cancers,” said Helen Collins, MD, executive vice president and chief medical officer of Five Prime, in a statement. “With these data in hand, we plan to continue to collaborate with regulatory agencies on next steps, initiate a global phase 3 trial in gastric cancer, and begin studying bemarituzumab in other epithelial cancers that overexpress FGFR2b.”

REFERENCE

Phase 2 FIGHT Trial Results Presented at ASCO GI Validate Importance of FGFR2b Overexpression and Reinforce Potential of Bemarituzumab Plus Chemotherapy as a Frontline Targeted Treatment for FGFR2b+ Gastric and GEJ Cancers [news release]. Business Wire; January 15, 2021. https://www.businesswire.com/news/home/20210115005136/en. Accessed January 25, 2021.