- Not intended for US-, Canada- or UK-based media

Merck, a leading science and technology company, today announced topline data 
from the Phase II INTR@PID BTC 047 study evaluating bintrafusp alfa as a 
monotherapy in the second-line treatment of patients with locally advanced or 
metastatic biliary tract cancer (BTC) who have failed or are intolerant of 
first-line platinum-based chemotherapy. 

In the study of 159 patients, bintrafusp alfa demonstrated single-agent 
efficacy and durability with a manageable safety profile after more than nine 
months of follow-up, with an Independent Review Committee (IRC)-adjudicated 
objective response rate (ORR) of 10.1% (95% CI: 5.9% to 15.8%) per RECIST 1.1. 
Though single-agent activity was observed, the study did not meet the 
pre-defined threshold that would have enabled regulatory filing for BTC in the 
second line setting. The results will be submitted for presentation at an 
upcoming medical meeting or publication.

"Given the high unmet treatment need in BTC, where single agent immunotherapy 
in PD-L1 all comers has shown an ORR of 5.8%, we are encouraged by the single 
agent clinical activity of bintrafusp alfa in this study as a second-line 
treatment," said Milind Javle, MD, professor of GI medical oncology, MD 
Anderson Cancer Center, and an investigator for the INTR@PID BTC 047 study. 
"The bintrafusp alfa 047 study is one of the most important clinical 
investigations conducted for chemo-refractory biliary cancers, and I would like 
to thank the patients, families, and study team for their valuable 
participation." 

"This study demonstrates single-agent activity with bintrafusp alfa in locally 
advanced or metastatic BTC, a disease that has been historically difficult to 
treat," said Danny Bar-Zohar, M.D., Global Head of Development for the 
Healthcare business sector of Merck. "The data will contribute to our 
understanding of addressing both TGF-Beta and PD-L1 inhibition in the tumor 
microenvironment."

A Phase II/III study of bintrafusp alfa in combination with chemotherapy as a 
first-line treatment for BTC (INTR@PID BTC 055), which is assessing a different 
hypothesis than the second-line monotherapy study, has completed enrollment in 
the Phase II portion and is currently ongoing.

*Bintrafusp alfa is currently under clinical investigation and not approved for 
any use anywhere in the world.

About Biliary Tract Cancer (BTC)
BTCs are a group of rare, aggressive gastrointestinal cancers associated with 
poor outcomes and limited treatment options. There is currently no globally 
accepted standard of care in the second-line setting and chemotherapy as well 
as immunotherapies have demonstrated low response rates in BTC. 
Epithelial-to-mesenchymal transition (EMT), a hallmark of tumor progression and 
drug resistance, plays an important role in BTC, and has been shown to be 
triggered by TGF-Beta signaling.

About Bintrafusp Alfa 
Bintrafusp alfa (M7824), discovered in-house at Merck, and currently in 
clinical development through a strategic alliance with GSK, is a potential 
first-in-class investigational bifunctional fusion protein designed to 
simultaneously block two immunosuppressive pathways, TGF-Beta and PD-L1, within 
the tumor microenvironment. This bifunctional approach is thought to control 
tumor growth by potentially restoring and enhancing anti-tumor responses. In 
preclinical studies, bintrafusp alfa has demonstrated antitumor activity both 
as monotherapy and in combination with chemotherapy. Based on its mechanism of 
action, bintrafusp alfa offers a potential targeted approach to addressing the 
underlying pathophysiology of difficult-to-treat cancers.

About the INTR@PID Clinical Trial Program
INTR@PID is a global clinical trial program investigating the potential 
co-localized, dual inhibition of TGF-Beta and PD-L1 with bintrafusp alfa 
(M7824) in multiple tumor types. Current clinical trial information can be 
found on the INTR@PID website at www.intrapidclinicaltrials.com. To date, 
globally more than 1,300 patients with various types of solid tumors have 
received bintrafusp alfa in the INTR@PID clinical development program.

The INTR@PID clinical development strategy is comprehensive and is pursuing 
non-redundant hypotheses grounded in preclinical and early clinical data 
findings that continue to be explored and may yield clinically meaningful 
insights to patients in need, including exploring settings where simultaneous, 
synchronized targeting of TGF-Beta and PD-L1 may offer the key to expanding the 
potential of immunotherapy; focusing on opportunities where PD-1/PD-L1 has 
suboptimal clinical activities and pathogenesis linked to TGF-Beta biology; and 
targeting specific tumors with biomarkers with a strong link to TGF-Beta 
signaling pathway.

All Merck Press Releases are distributed by e-mail at the same time they become 
available on the Merck Website. Please go to www.merckgroup.com/subscribe to 
register online, change your selection or discontinue this service. 

About Merck
Merck, a leading science and technology company, operates across healthcare, 
life science and electronics. Around 58,000 employees work to make a positive 
difference to millions of people's lives every day by creating more joyful and 
sustainable ways to live. From advancing gene editing technologies and 
discovering unique ways to treat the most challenging diseases to enabling the 
intelligence of devices - the company is everywhere. In 2020, Merck generated 
sales of EUR17.5 billion in 66 countries.

Scientific exploration and responsible entrepreneurship have been key to 
Merck's technological and scientific advances. This is how Merck has thrived 
since its founding in 1668. The founding family remains the majority owner of 
the publicly listed company. Merck holds the global rights to the Merck name 
and brand. The only exceptions are the United States and Canada, where the 
business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma 
in life science, and EMD Electronics.

Your Contacts 
Media Relations 
gangolf.schrimpf@merckgroup.com  
Phone: +49 6151 72-9591 

Investor Relations 
investor.relations@merckgroup.com  
Phone: +49 6151 72-3321 

Logo - https://mma.prnewswire.com/media/1136775/Merck_Logo.jpg  

SOURCE  Merck