Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

4505 - M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-_, in Asian patients with pretreated biliary tract cancer: Preliminary results from a phase 1 trial


21 Oct 2018


Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology


Clinical Research

Tumour Site

Hepatobiliary Cancers


Changhoon Yoo


Annals of Oncology (2018) 29 (suppl_8): viii205-viii270. 10.1093/annonc/mdy282


C. Yoo1, D. Oh2, H.J. Choi3, M. Kudo4, M. Ueno5, S. Kondo6, L. Chen7, M. Osada8, C. Helwig9, I. Dussault10, M. Ikeda11

Author affiliations

  • 1 Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 2 Medical Oncology, Seoul National University Hospital, 110-744 - Seoul/KR
  • 3 Medical Oncology, Yonsei University College of Medicine, 120-752 - Seoul/KR
  • 4 Department Of Gastroenterology And Hepatology, Kindai University Faculty of Medicine, Osaka/JP
  • 5 Department Of Gastroenterology, Hepatobiliary And Pancreatic Medical Oncology Division, Kanagawa Cancer Center, 2410815 - Yokohama/JP
  • 6 Department Of Hepatobiliary And Pancreatic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 7 Internal Medicine, National Cheng-Kung University Hospital, National Institute of Cancer Research, Tainan/TW
  • 8 Medical Oncology, Merck Serono, Tokyo/JP
  • 9 Biostatistics, Merck KGaA, Darmstadt/DE
  • 10 Clinical Biomarkers, Immuno-oncology, EMD Serono, Billerica/US
  • 11 Department Of Hepatobiliary And Pancreatic Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP

Abstract 4505


Biliary tract cancers (BTCs) are a group of aggressive cancers with limited treatment options. Overall response rates (ORRs) with 2L chemotherapy in BTC are <10%, and no standard of care exists. M7824 is an innovative first-in-class bifunctional fusion protein composed of a human anti–PD-L1 IgG1 monoclonal antibody fused with 2 extracellular domains of the transforming growth factor β (TGF-β) receptor II (a TGF-β “trap”). We report on the safety and efficacy of M7824 in patients (pts) with pretreated BTC.


In this expansion cohort of the ongoing phase 1, open-label trial NCT02699515, Asian pts who progressed after platinum-based 1L treatment received M7824 1200 mg q2w until confirmed progressive disease, unacceptable toxicity or trial withdrawal. The primary objective is safety/tolerability; secondary objectives include assessment of best overall response per RECIST v1.1. Tumor cell PD-L1 expression was evaluated (antibody clone 73-10).


As of March 20, 2018, 30 pts with pretreated BTC received M7824 for a median duration of 8.9 (range, 2-57.6) wk; 5 pts remained on treatment. The most common treatment-related adverse events (TRAEs) were pyrexia, maculopapular rash (both 13.3%) rash and lipase increase (both 10%); 10 pts (33.3%) experienced grade ≥3 TRAEs. 3 deaths due to AEs were reported; 1 death was due to septic shock (bacteremia, etiology unknown) after 14 doses, and 2 deaths due to interstitial lung disease (ILD), 1 on treatment after 3 doses and 1 with grade 3 ILD after 3 doses that recovered, initiated chemotherapy due to PD, and worsened with death 6 months after initial ILD diagnosis and last M7824 dose. 7 pts had an objective response (ORR, 23.3%, including one late PR pending confirmation), with 4 of 6 PRs ongoing (0.7+, 2.8, 3.9+, 5.5+, 5.6, and 6.9+ mo) and 1 CR ongoing for 5.6+ mo. 1 additional pt had ongoing PR for 7.6+ mo after initial pseudoprogression. Confirmed ORR by PD-L1 expression was 25% and 15.4% in pts with PD-L1 + (≥1%) and PD-L1− tumors, respectively.


M7824 monotherapy has promising efficacy in Asian pts with pretreated BTC, including long-lasting responses in 8 of 30 pts (27%).

Clinical trial identification


Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany.


Merck KGaA, Darmstadt, Germany.

Editorial Acknowledgement

Medical writing support was provided by ClinicalThinking, and was funded by Merck KGaA, Darmstadt, Germany.


C. Yoo: Research funding: CKD pharm, Shire; Honoraria: Bayer, Ipsen. D-Y. Oh: Research funding: AstraZeneca. M. Ueno: Research Funding: Taiho Pharmaceutical, Shire, Daiichi Sankyo, Eisai, AstraZeneca, Ono Pharmaceutical, MSD, Merck Serono, NanoCarrier, Dainippon Sumitomo Pharma, Incyte; Honoraria: Taiho Pharmaceutical, Yakult Honsha, AstraZeneca, Novartis, Lilly, Teijin Pharma, Shire, Ono Pharmaceutical. S. Kondo: Research Funding: MSD, Bayer, Aslan, Pfizer, AstraZeneca, Lilly. M. Osada: Employee: Merck Serono, Tokyo, Japan. C. Helwig: Employee: Merck KGaA, Germany; Equity ownership: Merck KGaA, Germany. I. Dussault: Employee: EMD Serono. M. Ikeda: Research Funding: Bayer Yakuhin, Kyowa Hakko Kirin, Yakult, Taiho Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, Eisai, AstraZeneca, Zeria Pharmaceutical, Baxter, Chugai Pharmaceutical, Bristol Myers Squibb, Merck Serono, Kowa, Nano Carrier, ASLAN Pharmaceuticals; Honoraria: Novartis Pharma, Bayer Yakuhin, Bristol-Myers Squibb, Abbott Japan, Eisai, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Daiichi-Sankyo, Yakult, Otsuka Pharmaceutical, Nobelpharma; Membership board of directors or advisory committees: Nano Carrier, Bayer Yakuhin, Eisai, Kyowa Hakko Kirin, Novartis Pharma, Shire, MSD. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.