Shares in Five Prime Therapeutics jumped 300% on the back of data from a phase 2 trial that gave bemarituzumab as a front-line treatment to patients with advanced gastric and gastroesophageal junction cancers.
Gastric cancer is the third most common cause of cancer death globally, and patients have suffered from a dearth of new drugs. It is now more than a decade since the FDA approved a new front-line treatment, and chemotherapy remains the standard of care for most HER2-negative patients. Five Prime, which has been dogged by setbacks in recent years, wants to change the treatment paradigm, leading it to run a phase 2 trial of anti-FGFR2b antibody bemarituzumab.
Investigators enrolled 155 people with FGFR2b-positive tumors, a subpopulation that accounts for 30% of all non-HER2-positive patients, and randomized them to receive bemarituzumab or placebo on top of chemotherapy. The trial cleared the pre-specified bar for statistical significance against all three efficacy endpoints, although the p-values were higher than the 0.05 that typically serves as the cutoff for effectiveness.
Progression-free survival in patients who received bemarituzumab on top of chemotherapy was 9.5 months, more than two months longer than the figure in the control arm. The difference worked out at a p-value of 0.073 and a hazard ratio of 0.68. Ahead of the data readout, Five Prime Chief Medical Officer Helen Collins, M.D., told investors previously successful gastric cancer trials achieved hazard ratios of around 0.7.
The progression-free survival hazard ratio in the Bristol Myers Squibb Opdivo gastric cancer trial that read out earlier this year was 0.68, reflecting the 1.7 month improvement linked to the checkpoint inhibitor. Further back, Genentech won FDA approval for Herceptin in gastric cancer on the strength of a trial with a hazard ratio of 0.71 and a 1.2 month improvement in progression-free survival.
Those comparisons suggest bemarituzumab is promising in the context of the historical struggle to drive major improvements in the outcomes of gastric cancer patients. There is scope for the overall survival data to offer even more encouragement.
As of the cutoff, Five Prime was yet to reach the median overall survival in the bemarituzumab arm. The median overall survival in the control group was 12.9 months, leading Five Prime to calculate the hazard ratio at 0.58. Herceptin and Opdivo, respectively, drove 2.7 and 3.3 month improvements in overall survival, resulting in hazard ratios of 0.74 and 0.71. Five Prime also saw improvements in response rate that are in line with the results achieved by Herceptin and Opdivo.
As expected, corneal and stomatitis adverse events were more frequent in the bemarituzumab arm, but no patients suffered retinal detachment or hyperphosphatemia. The overall incidence of adverse events was similar across the treatment and control cohorts, although one-third of people stopped taking bemarituzumab due to adverse events and 12% reduced dosing. Five percent of participants discontinued placebo.
The unmet need in gastric cancer suggests the safety and tolerability issues may be manageable. The data set also offers encouragement for Five Prime as it considers developing bemarituzumab in other diseases with significant numbers of FGFR2b-positive patients, including non-small cell lung cancer and ovarian cancer.
Editor’s note: This story has been updated to correct the number of patients enrolled in the study.