Merck's Bintrafusp Alfa (M7824), a Next-Generation PD-L1/TGF-β Bispecific Fusion Protein, Receives Chinese Clinical Approval for Cervical Cancer

On March 24, the CDE’s list of clinical trial implicit approvals showed that Merck’s bispecific antibody M7824 (MSB0011359C) had been approved for clinical trials, with cervical cancer as the indication.

M7824 is a bifunctional fusion protein that acts as a PD-L1/TGF-β bispecific antibody, composed of two distinct domains. One end features an antibody structure (Y) capable of recognizing and binding to PD-L1, similar to approved PD-L1 antibodies such as durvalumab, avelumab, and atezolizumab; the other end consists of a type II TGF-β receptor fusion protein (Trap) that binds to TGF-β, thereby sequestering it and reducing pro-tumorigenic TGF-β levels within tumor tissues and their microenvironment. Given this unique mechanism of action, M7824 is referred to as a second-generation or enhanced PD-1 inhibitor.

At the 2018 ASCO Annual Meeting, Merck presented multiple clinical study updates on M7824, one of which demonstrated the efficacy of M7824 in treating HPV-positive tumors. The study enrolled 17 patients with HPV-associated cancers, including anal cancer, cervical cancer, and a small number of head and neck squamous cell carcinoma cases. Among them, 12 patients had confirmed HPV infection and were treated with varying doses of M7824. Of these 12 patients with confirmed HPV infection, one achieved complete tumor regression, four showed significant tumor shrinkage, and one had stable disease without progression, resulting in an overall objective response rate of 41.7%.

Currently, clinical studies of M7824 are being conducted simultaneously across multiple cancer types, with the biliary tract cancer (BTC) indication having received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA). Existing clinical data have demonstrated favorable outcomes for M7824 in various refractory cancers, including advanced non-small cell lung cancer (NSCLC), human papillomavirus (HPV)-associated cancers, biliary tract cancer, and gastric cancer.

In China, M7824 is currently conducting two international multicenter clinical trials, including Phase II trials for cholangiocarcinoma and advanced non-small cell lung cancer.

Original Title: Second-Generation PD-1: M7824 Approved for Clinical Trials in China, Indication: Cervical Cancer