Zai Lab and Amgen's FGFR2b-Targeted Monoclonal Antibody Bemarituzumab Receives Breakthrough Therapy Designation in Both China and the U.S. for First-Line Treatment of Gastric and GEJ Cancers

September 15, 2021 /BioonBIOON/ --Zai Lab recently announced,The Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) to bemarituzumab (FPA144 Injection)., in combination with the modified FOLFOX6 chemotherapy regimen (mFOLFOX6: 5-fluorouracil + calcium folinate + oxaliplatin), as first-line therapy for patients with fibroblast growth factor receptor 2b (FGFR2b)-overexpressing, HER2-negative, metastatic or locally advanced gastric and gastroesophageal junction (GEJ) cancer.

bemarituzumab (anti-FGFR2b monoclonal antibody) was developed by Five Prime Therapeutics,Zai Lab holds the exclusive license for Greater China.. In early March this year, Amgen announced that it had entered into a definitive agreement with Five Prime to acquire the latter's shares in an all-cash transaction at $38 per share, representing a total equity value of approximately $1.9 billion. On April 16, Amgen announced that the acquisition had been successfully completed. In addition to bemarituzumab, Five Prime's pipeline also for Amgen'sTumorSupplements the pipeline.

In April this year, the U.S. FDA granted bemarituzumab BTD:In combination with the modified FOLFOX6 chemotherapy regimen, first-line treatment based onFDAApproved Companion DiagnosticDiagnosisAnalysis shows at least 10%TumorPatients with FGFR2b-overexpressing, HER2-negative, metastatic and locally advanced gastric or GEJ adenocarcinoma.

In China and the United States, bemarituzumab was granted BTD, both based on the results of the Phase 2 FIGHT trial. Data indicate that,In the aforementioned patient population, first-line treatment with bemarituzumab + mFOLFOX6 demonstrated clinically significant and substantial benefits compared with placebo + mFOLFOX6, significantly prolonging progression-free survival (PFS) and overall survival (OS) and improving the objective response rate (ORR), all of which met pre-specified statistical significance.. Further analysis showed,Patient benefit is positively correlated with the proportion of FGFR2b+ tumor cells., confirming the importance of the FGFR2b target and the activity of bemarituzumab against this target. The Breakthrough Therapy Designation for bemarituzumab was based on data from this patient subset, pathologyDiagnosisin the immunohistochemistry (IHC) testing showed that at least 10% ofTumorCells overexpress FGFR2b.

bemarituzumab Mechanism of Action (Click the image to view a larger version)

Globally, every year, newDiagnosisGastric cancer cases exceed 1 million, with approximately half occurring in China. Nearly 88% of patients with advanced gastric cancer and GEJ cancer are HER2-negative, of whom approximately 30% exhibit FGFR2b overexpression.

Bemarituzumab is a first-in-class targeted antibody that blocks FGF binding to and activation of FGFR2b, inhibits multiple downstream tumor-promoting signaling pathways, and potentially delays cancer progression.Currently, bemarituzumab is being developed for gastric cancer and GEJ cancer as a treatment for FGFR2b overexpression.Tumortargeted therapy.

Zai Lab holds the exclusive license to develop and commercialize bemarituzumab in Greater China, and collaborated with Five Prime (subsequently acquired by Amgen) to conduct the Phase 2 FIGHT trial in Greater China.

Amgen plans to initiate the registrational program for bemarituzumab in the fourth quarter of 2021. Clinical development of bemarituzumab in other FGFR2b-overexpressing solid tumors (including squamous non-small cell lung cancer) is ongoing.

FIGHT Clinical Data (Click image to view larger image)

The Phase 2 FIGHT trial is the first study to evaluate targeting FGFR2b overexpression in cancer. As a first-line treatment, bemarituzumab demonstrated clinical significance at key endpoints in patients with advanced gastric or gastroesophageal cancer.

FIGHT is a global, randomized, double-blind, placebo-controlled study, in newDiagnosisconducted in patients with fibroblast growth factor receptor 2b-positive (FGFR2b+), HER2-negative, advanced gastric or gastroesophageal junction (GEJ) cancer to evaluate the efficacy and safety of bemarituzumab versus placebo, each in combination with chemotherapy (mFOLFOX6), as first-line treatment. The trial enrolled 155 patients across 15 countries in Asia, the European Union, and the United States, of whom 77 were randomized to the bemarituzumab treatment group (bemarituzumab + mFOLFOX6) and 78 to the placebo group (placebo + mFOLFOX6).

Results showed that in the patient population with FGFR2b overexpression in at least 10% of tumor cells, patients in the bemarituzumab group demonstrated clinically significant and substantial improvements compared with the placebo group in the primary endpoint of progression-free survival (PFS) and the secondary endpoint of overall survival (OS). Additional analyses showed that the treatment benefit was associated with FGFR2b+TumorThe percentage of cells showed a positive correlation, confirming the importance of the FGFR2b target and the activity of bemarituzumab against this target.

The specific data are: (1)For the primary endpoint PFS, progression-free survival was significantly prolonged in the bemarituzumab group compared with placebo (median PFS: 14.1 months vs 7.3 months), with a 56% reduction in the risk of disease progression or death.（HR=0.44；95%CI:0.25-0.77）。（2）For the secondary endpoint of OS, the bemarituzumab group demonstrated a significant prolongation compared with placebo (median OS: not reached [NR] vs. 11.1 months), with a 59% reduction in the risk of death.(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