Zai Lab/Amgen's FGFR2b targeted monoclonal antibody has been certified as a breakthrough therapy in China and the U.S.

Zai Lab announced recently that CDE has granted bemarituzumab (FPA144 injection) breakthrough therapy designation (BTD), combined with an improved FOLFOX6 chemotherapy regimen (mFOLFOX6: fluoropyrimidine + leucovorin + oxaliplatin), as a first-line treatment for fibroblasts Growth factor receptor 2b (FGFR2b) overexpression, HER2-negative, metastatic and locally advanced gastric and gastroesophageal junction (GEJ) cancer patients
.

bemarituzumab (anti-FGFR2b monoclonal antibody) is developed by Five Prime Therapeutics, and Zai Lab has an exclusive license in Greater China
.

At the beginning of March this year, Amgen announced that it had reached a final agreement with Five Prime to acquire the latter's shares in cash at a price of $38 per share, corresponding to a total equity of approximately $1.

In April of this year, the US FDA granted bemarituzumab BTD: combined with a modified version of FOLFOX6 chemotherapy regimen, first-line treatment based on FDA-approved companion diagnostic analysis showed that at least 10% of tumor cells overexpress FGFR2b, HER2-negative, metastatic and locally advanced gastric or GEJ adenocarcinoma patients
.

In China and the United States, bemarituzumab obtained BTD based on the results of the Phase 2 FIGH trial
.

Data show that in the above-mentioned patient population, compared with placebo+mFOLFOX6, bemarituzumab+mFOLFOX6 first-line treatment shows clinically significant and substantial benefits, significantly prolonging progression-free survival (PFS) and overall survival (OS), and improving The objective response rate (ORR) has reached the pre-set statistical significance

bemarituzumab mechanism of action

Globally, there are more than 1 million newly diagnosed gastric cancer cases each year, and about half of the cases occur in China
.

Nearly 88% of patients with advanced gastric cancer and GEJ cancer are HER2-negative, and about 30% of them show FGFR2b overexpression

bemarituzumab is a first-in-class targeting antibody that prevents FGF from binding and activating FGFR2b, inhibits a variety of downstream pro-tumor signaling pathways, and potentially delays cancer progression
.

Currently, bemarituzumab is being developed in gastric cancer and GEJ cancer as a targeted therapy for FGFR2b overexpressing tumors

Zai Lab has the exclusive license to develop and commercialize bemarituzumab in the Greater China region, and cooperated with Five Prime (later acquired by Amgen) to conduct a two-phase FIGH test in the Greater China region
.

Amgen plans to start the registration project of bemarituzumab in the fourth quarter of 2021
.

The clinical research plan of bemarituzumab in other FGFR2b overexpressing solid tumors (including squamous non-small cell lung cancer) is ongoing

FIGHT clinical data

The Phase 2 FIGHT trial is the first study to evaluate the overexpression of FGFR2b in targeted cancers
.

As a first-line treatment, bemarituzumab has shown clinical significance as a key endpoint in patients with advanced gastric cancer or gastroesophageal cancer

FIGHT is a global, randomized, double-blind, placebo-controlled study in newly diagnosed fibroblast growth factor receptor 2b positive (FGFR2b+), non-HER2 positive, advanced gastric or gastroesophageal junction (GEJ) cancer patients To evaluate the efficacy and safety of bemarituzumab and placebo combined with chemotherapy (mFOLFOX6) for first-line treatment
.

The trial enrolled 155 patients in 15 countries in Asia, the European Union, and the United States, of which 77 were randomly assigned to the bemarituzumab treatment group (bemarituzumab+mFOLFOX6), and 78 patients were assigned to the placebo group (placebo+mFOLFOX6)

The results showed that in the patient population with at least 10% of tumor cells overexpressing FGFR2b, compared with the placebo group, patients in the bemarituzumab group showed progression-free survival (PFS) primary endpoints and overall survival (OS) secondary endpoints.
A clinically significant and substantial improvement
.

Additional analysis showed that treatment benefit was positively correlated with the percentage of FGFR2b+ tumor cells, confirming the importance of the FGFR2b target and the activity of bemarituzumab on this target

The specific data are: (1) In terms of the primary endpoint of PFS, the bemarituzumab group was significantly prolonged compared with placebo (median PFS: 14.
1 months vs 7.
3 months), and the risk of disease progression or death was reduced by 56% (HR=0.
44; 95%) CI: 0.
25-0.
77)
.
(2) In terms of secondary endpoint OS, the bemarituzumab group was significantly prolonged compared with placebo (median OS: not reached [NR] vs 11.
1 months), and the risk of death was reduced by 59% (HR=0.
41; 95%CI: 0.
22- 0.
79)
.
(Bioon.
com)

Original source: Zai Lab Announces Breakthrough Therapy Designation Granted for Bemarituzumab (FPA144) in China

Original source: Zai Lab Announces Breakthrough Therapy Designation Granted for Bemarituzumab (FPA144) in China