Bemarituzumab response for gastric/GEJ cancers correlates with FGFR2b levels

Presented by

Prof. Zev Wainberg, UCLA, USA

Conference

ASCO GI 2021

Trial

Phase 2, FIGHT

An update of the randomised placebo-controlled phase 2 FIGHT trial continued to underscore the potential of bemarituzumab plus chemotherapy as a frontline therapy in FGFR2b-overexpressing gastric and gastroesophageal junction (GEJ) adenocarcinomas. The primary and key secondary endpoints demonstrated statistically significant and clinically meaningful improvements, with a 56% reduction in disease progression.

Prof. Zev Wainberg (UCLA, USA) presented the updated results of the randomised phase 2 FIGHT trial (NCT03694522), which evaluated bemarituzumab plus mFOLFOX6 chemotherapy versus placebo plus mFOLFOX6 chemotherapy in patients with fibroblast growth factor receptor 2b (FGFR2b)-positive, HER2-negative frontline advanced and metastatic gastric or GEJ cancers [1]. Bemarituzumab (anti-FGFR2b) is a first-in-class targeted antibody for tumours overexpressing FGFR2b. The primary outcome of this study was progression-free survival (PFS). Key secondary endpoints were overall survival (OS) and overall response rate (ORR).

FGFR2b-positivity was determined by centrally performed prospective immunohistochemistry (IHC) for FGFR2b overexpression and/or a circulating tumour DNA blood assay demonstrating FGFR2 gene amplification. Of the 910 evaluated patients, 275 (30%) were FGFR2b-positive. Eventually, 155 patients were randomised.

Prof. Wainberg reported a positive correlation between benefit and the percentage of FGFR2b-positive tumour cells. For patients with IHC results showing FGFR2b overexpression in at least 10% of the sample, the median PFS was 14.1 months for the bemarituzumab cohort, compared with 7.3 months for the placebo cohort (HR 0.44; 95% CI 0.25-0.77). The 1-year PFS rates were 57.0% and 26.4% in the bemarituzumab and placebo arms, respectively. In those with IHC FGFR2b overexpression in at least 5% of cells, the median PFS was 10.2 months in the bemarituzumab arm versus 7.3 months with the placebo arm (HR 0.54; 95% CI 0.33-0.87). The 1-year PFS rates were 56.3% and 28.6%, respectively. Overall, in the intent-to-treat population, the median PFS was 9.5 months and 7.4 months for the bemarituzumab and placebo arms, respectively (HR 0.68; 95% CI 0.44-1.04; P=0.0727). The 1-year PFS rates were 52.5% and 33.8%, respectively. The median OS was not reached in the bemarituzumab arm, versus 12.9 months in the placebo arm (HR 0.58; 95% CI 0.35-0.95; P=0.0268). Again, the percentage of FGFR2b-positive cells was indicative of OS; in the patients whose tumours were at least 5% FGFR2b-positive, the median OS was not reached with bemarituzumab versus 12.5 months with the placebo arm (HR 0.52; 95% CI 0.30-0.91), and for 10% or more FGFR2b-positivity the benefit was even more marked (HR 0.41; 95% CI 0.22-0.79).The ORR was 47% in the bemarituzumab arm, and 33% with placebo.

Corneal events, commonly associated with FGFR inhibition, were reported more frequently in the bemarituzumab arm (67.1% vs 10.4%), with the most common in the bemarituzumab arm being dry eye (26.3%), keratitis (15.8%), and punctate keratitis (14.5%). Stomatitis (31.6% vs 13.0%) and elevated transaminases (34.2% vs 19.5%) were also more common in the bemarituzumab arm. Grade 3 and higher adverse events (82.9% vs 74.0%), serious adverse events (31.6% vs 36.4%), and deaths (6.6% vs 5.2%) were comparable across arms.

Overall, these results justify a prospective, randomised phase 3 trial of bemarituzumab.

Wainberg ZA, et al. Randomized double-blind placebo-controlled phase 2 study of bemarituzumab combined with modified FOLFOX6 (mFOLFOX6) in first-line (1L) treatment of advanced gastric/gastroesophageal junction adenocarcinoma (FIGHT). ASCO Gastrointestinal Cancers Symposium 2021, 15-17 January. Abstract 160.

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