Merck Reports Promising Clinical Activity of Bintrafusp Alfa, a Bifunctional TGF-β/PD-L1 Fusion Protein, in Second-Line Treatment of Biliary Tract Cancer

March 16, 2021 News /BioValleyBIOON/ -- Merck KGaA recently announced top-line data from the Phase 2 INTR@PID BTC 047 study. This study evaluated bintrafusp alfa (M7824) as a monotherapy for second-line treatment in patients with locally advanced or metastatic biliary tract cancer (BTC) who had experienced failure or intolerance to first-line platinum-based chemotherapy.

A total of 159 patients were enrolled in this study. After more than 9 months of follow-up, the data confirmed the efficacy and durability of bintrafusp alfa monotherapy, with a manageable safety profile. The objective response rate (ORR) assessed by the Independent Review Committee (IRC) according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) was 10.1% (95% CI: 5.9–15.8). Although activity of bintrafusp alfa monotherapy was observed, the study did not meet the prespecified threshold that would have enabled regulatory filing for second-line treatment of biliary tract cancer (BTC). The results of this study will be presented at an upcoming medicalMeetingpublished online or in peer-reviewed journals.

Investigators of the INTR@PID BTC 047 study, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterTumorProfessor Milind Javle stated, “Given the high unmet medical need in the treatment of BTC and the fact that single-agent immunotherapy has shown an overall response rate (ORR) of only 5.8% across all PD-L1 expression levels, we are encouraged by the clinical activity of bintrafusp alfa as a single agent in the second-line setting in this study. The bintrafusp alfa 047 study is one of the most significant clinical studies conducted in chemotherapy-refractory cholangiocarcinoma. I would like to thank the patients, their families, and the research team for their invaluable participation.”

Danny Bar Zohar, M.D., Global Head of Development for Merck Healthcare Business Sector, stated: “This study demonstrates that bintrafusp alfa has single-agent activity in locally advanced or metastatic BTC, a disease that has historically been difficult to treat. These data will help us understand”Tumor“Inhibitory Effects of TGF-β and PD-L1 in the Microenvironment.”

Currently, a phase 2/3 study (INTR@PID BTC 055) is evaluating bintrafusp alfa in combination with chemotherapy as first-line treatment for biliary tract cancer (BTC). This study is assessing a hypothesis distinct from that of the second-line monotherapy studies; enrollment for the phase 2 portion has been completed, and the study is ongoing.

Cholangiocarcinoma - Cholangiocarcinoma

Biliary tract cancer (BTC) is an umbrella term for a group of rare, aggressive gastrointestinal cancers, including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC). It is estimated that 16,000 BTC cases are diagnosed annually in the United States, with most patients presenting at an advanced stage. BTC carries a poor prognosis and limited treatment options; the median overall survival for patients with advanced disease is less than one year, the objective tumor response rate to standard chemotherapy is typically below 10%, and responses are often short-lived. Currently, there is no globally accepted standard for second-line therapy, and both chemotherapy and immunotherapy exhibit low response rates in BTC. Epithelial–mesenchymal transition (EMT) isTumormarkers of progression and resistance, which play a crucial role in BTC and have been shown to be triggered by TGF-β signaling.

Bintrafusp alfa (M7824) is a bifunctional immunotherapy discovered internally by Merck KGaA, currently being developed in collaboration withGlaxoSmithKlinestrategic alliance for clinical development. This drug combines a transforming growth factor-beta (TGF-β) trap and an anti-PD-L1 mechanism into a single fusion protein, designed to simultaneously block two immunosuppressive pathways, TGF-β and PD-L1, within the tumor microenvironment. This bifunctional immunotherapy is believed to control tumor growth by potentially restoring and enhancing anti-tumor immune responses. In preclinical studies, bintrafusp alfa has demonstrated efficacy as both monotherapy and in combination with chemotherapy.Tumoractivity. Based on its mechanism of action, bintrafusp alfa has the potential to provide a targeted approach to addressing the underlying pathophysiology of refractory cancers. (Bioon.com)

Original Source: Merck Reports Topline Data for Bintrafusp Alfa as Second-Line Monotherapy Treatment in Biliary Tract Cancer