By Jennifer Lubell
Adding bemarituzumab to modified FOLFOX (mFOLFOX) chemotherapy significantly improves survival and response rates for patients with advanced gastric cancer. The approach was associated with an increase in corneal adverse events and stomatitis.
Zev Wainberg, MD, presented these findings at the American Society of Clinical Oncology’s 2021 Gastrointestinal Cancers Symposium (Abstract 160).
The first-line treatment of advanced gastric/gastroesophageal junction adenocarcinoma (FIGHT) trial is the first study to target the overexpression of FGFR2b in any cancer, according to Dr. Wainberg, who is the co-director of the UCLA Gastrointestinal Oncology Program. In this study, about 30% of patients overexpressed FGFR2b using a centrally performed immunohistochemistry (IHC) assay.
Bemarituzumab is a first-in-class humanized IgG1 monoclonal antibody that selectively binds to FGFR2b. It inhibits ligand binding and mediates antibody-dependent cell-mediated cytotoxicity. FGFR2b has been shown to be overexpressed in a wide variation, depending on the stage of the tumor and IHC assay used. A phase 1 study of bemarituzumab monotherapy in patients with refractory FGFR2b+ gastric cancer had a confirmed objective response rate of 18% and reported no serious side effects.
“We have known for a while that FGFR and FGFR2B, in particular, is a viable target in gastric cancer. Our approach using an antibody (bemarituzumab) with chemo was felt to be the best way to target this cancer,” Dr. Wainberg told OBR.
The FIGHT trial, a randomized, double-blind placebo-controlled phase 2 study, enrolled patients who had no prior therapy for unresectable locally advanced or metastatic disease and whose gastric cancer was not HER2+. Tumors positive for FGFR2b overexpression by centrally performed IHC or for FGFR2 amplification by circulating tumor DNA (ctDNA) also determined eligibility.
Among 910 patients whose tumors were evaluated, 275 (30%) were FGFR2b+. Investigators further screened 191 patients, then randomized 155 into two cohorts: 77 in the bemarituzumab plus mFOLFOX6 arm and 78 in the mFOLFOX6 plus placebo arm. Approximately 45% of patients in both arms received a single dose of mFOLFOX prior to randomization. Patients averaged 60 years of age. Overall, age, gender, race, and ethnicity did not differ much among the two groups.
Progression-free survival (PFS) was the primary endpoint; overall survival (OS) and response rate (ORR) were the secondary endpoints. Patients continued treatment until disease progression, intolerable toxicity, or death. The trial met all three endpoints.
“We showed a statistically significant improvement in progression-free survival, overall survival and overall response rate with FOLFOX plus bema over FOLFOX plus placebo,” Dr. Wainberg said.
PFS improved from 7.4 months to 9.5 months (Hazard Ratio [HR], 0.68; 95% CI 0.44-1.04; P=0.07).
The PFS and OS survival benefit rose with higher levels of overexpression of FGFR2b on tumor cells. ORR improved from 40% with placebo to 53% with bemarituzumab among patients with measurable disease.
The median duration of response also improved from 7.1 months in the placebo arm to 12.2 months in the bemarituzumab arm.
The findings demonstrate that bemarituzumab in combination with mFOLFOX has potential as a first-line treatment for advanced gastric cancer, Dr. Wainberg said. “I think this makes FGFR2B one of the most important targets in gastric cancer. Phase 3 trials are being planned,” Dr. Wainberg added.
Bemarituzumab patients experienced slightly higher grade 3 adverse events (AEs); 83% compared with 74% in the placebo arm. Overall, 34% of patients experienced toxicity requiring discontinuation of bemarituzumab, compared with 5% of patients on placebo.
Grade 3 stomatitis increased from 1.3% in the placebo arm to 9.2 % with bemarituzumab. Dry eye, seen in no patients with placebo, appeared in 2.6% of patients receiving bemarituzumab. The majority of these conditions were reversible, Dr. Wainberg said. No reported AEs of retinal detachment or hyperphosphatemia occurred in the bemarituzumab arm.