Gastric cancer has a new target: fibroblast growth factor receptor 2b (FGFR2b). Targeting FGFR2b with bemarituzumab plus chemotherapy led to clinically meaningful and statistically significant improvements in progression-free survival, overall survival, and response rates in the randomized phase II FIGHT trial of 155 previously untreated patients with advanced gastric or gastroesophageal junction cancer. These findings were presented by Zev Wainberg, MD, and colleagues at the 2021 Gastrointestinal Cancers Symposium (Abstract 160).

“The FIGHT trial is the first study to evaluate targeting overexpression of FGFR2b, and the only randomized dataset of any fibroblast growth factor receptor inhibitor in any malignancy,” said Dr. Wainberg, Assistant Professor of Medicine at the University of California, Los Angeles (UCLA) and Co-Director of UCLA's GI Oncology Program.

Zev Wainberg, MD

FIGHT Trial

Bemarituzumab is a first-in-class, humanized IgG1 monoclonal antibody that selectively binds to FGFR2b, inhibits ligand binding, and mediates antibody-dependent cell-mediated cytotoxicity. It was evaluated in the global, randomized, double-blind, placebo-controlled phase II FIGHT trial of patients with previously untreated, unresectable, locally advanced or metastatic gastric cancer that was not HER2-positive. All patients had tumors that expressed FGFR2b or had FGFR2 genetic amplifications.  

Of 910 previously untreated patients with gastric or gastroesophageal junction cancer whose tumors were evaluated, 275 (30%) were FGFR2b-positive. Ultimately, 155 patients were treated with modified FOLFOX6 (fluorouracil, leucovorin, oxaliplatin) and randomly assigned 1:1 to receive bemarituzumab 15 at mg/kg or placebo every 2 weeks with one additional bemarituzumab dose of 7.5 mg/kg on day 8. The primary endpoint was investigator-assessed progression-free survival.

Primary and Secondary Endpoints Met

The primary endpoint was met, with an improvement in median progression-free survival from 7.4 months with placebo to 9.5 months with bemarituzumab (hazard ratio [HR] = 0.68, P = .07). The secondary endpoint of overall survival was also met, with the median not being reached in the bemarituzumab arm compared to 12.9 months in the control arm (HR = 0.58, P = .03). Response rates increased from 40% to 53%, with median duration of response of 7.1 months with placebo vs 12.2 months with bemarituzumab.  

“Importantly, as FGFR2b expression increased, so too did benefit increase in groups receiving bemarituzumab, both for progression-free and overall survival,” said Dr. Wainberg.

Hazard ratios for the subgroup with the highest staining on immunohistochemistry (IHC 2+/3+ ≥ 10%) were 0.44 for progression-free survival and 0.41 for overall survival. 

Safety Profile

Overall, 34% of patients experienced toxicity requiring discontinuation of bemarituzumab, compared with 5% of patients on placebo, though exposure to bemarituzumab in both arms was similar (median = approximately 25 weeks). Of particular note was ocular toxicity, which is a known side effect of FGFR inhibitors.

Corneal events of any grade (mostly dry eye, keratitis, and punctate keratitis) were seen in 67% of patients in the bemarituzumab arm vs 10% of the placebo arm, with 24% vs 0% being grade ≥ 3. No cases of retinal detachment or hyperphosphatemia, however, occurred with the drug. Corneal toxicities resolved in 60% of patients at a median time to resolution of 27 weeks.

“In summary, we are very excited that this finding validates FGFR2 as an important target in gastric cancer. Our next steps are to move forward with the phase III trial to confirm these important results,” concluded Dr. Wainberg.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.