Merck Halts Phase II Study of M7824 (Bintrafusp Alfa) in First-Line Biliary Tract Cancer Due to Futility

Source: PharmaCube Info

Author: Shibei

On August 23, Merck announced that, based on the review by the Independent Data Monitoring Committee (IDMC), the company has decided to terminate the Phase II INTR@PID BTC 055 study due to the low likelihood of meeting the primary endpoint of overall survival (OS). The study was designed to evaluate the efficacy and safety of Merck’s TGF-β/PD-L1 bifunctional fusion protein bintrafusp alfa in combination with gemcitabine and cisplatin as first-line treatment for locally advanced or metastatic biliary tract cancer (BTC). No new safety signals were identified in the study.

It is understood that this marks the fourth Phase II/III clinical trial of bintrafusp alfa to fail this year. On January 15, the Phase II trial (NCT03436563) evaluating bintrafusp alfa in patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) solid tumors who experienced disease progression following prior immune checkpoint inhibitor (ICB) therapy failed to demonstrate antitumor activity and was subsequently terminated.

On January 20, the phase III INTR@PID Lung 037 trial comparing bintrafusp alfa versus pembrolizumab as first-line treatment for stage IV non-small cell lung cancer (NSCLC) with high PD-L1 expression was also terminated early due to the unlikelihood of meeting the co-primary endpoints.

On March 16, the phase II INTR@PID BTC 047 trial evaluating bintrafusp alfa monotherapy as second-line treatment for locally advanced or metastatic biliary tract cancer (BTC) was also terminated due to failure to meet the primary endpoint. The study enrolled 159 patients. After 9 months of follow-up, the objective response rate (ORR) assessed by the Independent Review Committee (IRC) was 10.1% (95% CI: 5.9%–15.8%), which did not meet the pre-specified criteria.

Bintrafusp alfa (M7824), discovered by Merck KGaA, is a potential first-in-class bifunctional fusion protein that simultaneously blocks the TGF-β and PD-L1 immunosuppressive pathways in the tumor microenvironment, thereby reversing immune suppression and enhancing the immune system's cytotoxic activity against cancer cells.

bintrafusp alfa structure

In February 2019, Merck KGaA and GSK entered into a global strategic collaboration to jointly develop M7824. Both parties will jointly be responsible for the global clinical development and commercialization of M7824, with all associated costs and profits shared equally between them.

Among drugs targeting the same target, Hengrui's SHR-1701 is currently in Phase III clinical trials, Mabwell's PM8001 is in Phase I/II studies, and CSPC's Y101 has submitted an IND application.