Amgen reports late-stage, first-line gastric cancer win for anti-FGFR2b mAb

More than four years since Amgen shelled out nearly $2 billion to acquire Five Prime and its FGFR2b-targeting monoclonal antibody (mAb), new data for bemarituzumab seem to back up the pharma's bet. 

Amgen reported top-line results from a Phase III gastric cancer study on Monday showing that the mAb met its main survival endpoint. While the drugmaker didn't share specifics behind the clinical win, it promised to provide detailed data at a future medical meeting.

The Phase III FORTITUDE-101 trial enrolled 547 patients with unresectable, locally advanced or metastatic non-HER2–positive, FGFR2b-overexpressing gastric or gastroesophageal junction (GEJ) cancer.

Participants were randomised to receive either first-line bemarituzumab plus chemotherapy (mFOLFOX6), or chemotherapy alone. 

Per a pre-specified interim analysis, the combo met its primary endpoint of a statistically significant and clinically meaningful improvement in overall survival (OS) compared with chemotherapy.

"Most patients with gastric cancer are diagnosed at an advanced stage, with poor prognosis, low survival rates and limited therapeutic options," said Jay Bradner, Amgen's EVP of R&D. The study results, he added, "mark a meaningful advance in the development of effective targeted therapy for gastric cancer."

The results seem to confirm Phase II findings, in which the mAb plus chemotherapy significantly improved progression-free survival and OS versus chemotherapy alone.

However, that trial also showed a higher rate of corneal and stomatitis adverse events (AEs) in patients who received bemarituzumab, with AEs of at least Grade 3 occurring in 82.9% of those in the experimental arm compared with 74% in the placebo group. In addition, 34.2% of patients discontinued treatment with bemarituzumab due to an AE, versus 5.2% of those taking placebo.

In the Phase III study, ocular AEs continued to occur "with greater frequency and severity" in the bemarituzumab arm. More than a quarter of patients who received the mAb experienced reduced visual acuity, punctate keratitis, anaemia, neutropenia, nausea, corneal epithelium defect or dry eye.

FORTITUDE-101 was supported by Zai Lab, which in 2017 exclusively licensed co-development and commercialisation rights for bemarituzumab from Five Prime in China, Hong Kong, Macau and Taiwan.

The partners are also conducting a Phase III study of bemarituzumab plus chemotherapy and Bristol Myers Squibb's Opdivo (nivolumab) as a first-line treatment for gastric cancer, with a data readout expected in the second half of the year.