Bemarituzumab Plus FOLFOX Superior to FOLFOX Alone Among Patients With FGFR2b-Positive Metastatic Gastric Cancer

Long-Term Follow-Up Results From the Phase 2 FIGHT Trial 

At the 2023 World Congress on Gastrointestinal Cancers, Zev Wainberg, MD, David Geffen School of Medicine at University of California – Los Angeles, California, presented the final analysis of the phase 2 FIGHT trial, which found bemarituzumab plus FOLFOX significantly improved PFS and OS among patients with FGFR2b >10% metastatic gastric cancer, compared with FOLFOX alone.

Dr Wainberg stated “Moving forward, the emphasis and primary analysis of the study will be performed in that group of patients who have [FGFRb] >10% so we’re trying to scrutinize this biomarker, which I think we’ve done somewhat successfully here, and now trying to determine the best effect size for this drug which will be in that group of patients with >10%.”

Transcript:

Hi, I am Dr Zev Wainberg, a GI medical oncologist from UCLA, Los Angeles, California, and at ESMO GI 2023 we analyzed the long-term results of the FIGHT trial.

The FIGHT trial was a trial targeting FGFR2b-positive metastatic gastric cancer. Primary results of the trial have been reported, I’ll briefly describe that: the trial took patients with newly diagnosed metastatic gastric cancer who were HER2-negative and looked for the impact of an FGFR2b antibody, the name of the drug is bemarituzumab, plus FOLFOX chemotherapy versus placebo plus FOLFOX chemotherapy. In order to determine which patients were the best ones to be treated, we'd already done a phase 1 and small phase 2 study that really showed the effect was in this group of patients who are FGFR2-positive as defined either by amplification, overexpression by immunochemistry, or ctDNA-positive as determined via a blood test. The results, which we published in the FIGHT trial showed that the group of patients who got FOLFOX plus bemarituzumab over FOLFOX plus placebo had an improvement in progression-free survival (PFS) and had an improvement in overall survival (OS) and, even though this was a phase 2 study, there were certain trends that were strongly suggestive of benefit in certain subgroups.

The purpose of this dataset presented today at ESMO GI 2023 was to look with longer follow-up, now at 2 years of follow-up, what trends start to be more obvious. And, in fact, we did isolate most of the effect to the FGFR2b >10% in any tumor cell subset. That means scrutinizing this biomarker cutoff from any positive FGFR2b staining, first to 5% and now in this analysis to 10%. This represents about 2/3 of the patients enrolled in the study and in total represents about 20% of HER2-negative gastric cancer. What we showed in this analysis that is where the best bang for your buck is with bemarituzumab plus chemotherapy. The group of patients who got the most benefit were those with the highest intense staining of this protein and we showed that the PFS was markedly improved with an improved hazard ratio in that group of patients but particularly, OS improved from about 12 months to about 24 months median [OS] in that group of patients who had FGFR2b >10% so, a real marked improvement there with a highly statistically significant P-value and hazard ratio.

This has very important implications because this drug bemarituzumab is now being studied in 2 large, randomized phase 3 trials and moving forward the emphasis and primary analysis of the study will be performed in that group of patients who have >10% so we're trying to scrutinize this biomarker, which I think we've done somewhat successfully here, and now trying to determine the best effect size for this drug, which will be in that group of patients with >10%.

All this data was presented at this congress which and hopefully we'll be able to enroll in these phase 3 studies and show the impact of this drug and get it out to patients. Thank you for your attention.

Source:

Wainberg Z, Kang Y, Lee K, et al. Bemarituzumab for treatment of previously untreated advanced and/or metastatic gastric and gastroesophageal cancer (GC): Final analysis of a randomized phase 2 trial (FIGHT). Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract SO-11