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Peer-Reviewed Publication
Nat Med2026;32(4):1267-1277.April 1, 2026Journal Article

Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial.

Zev A Wainberg1, Gulam A Manji2,3, Nathan Bahary4, Susanna V Ulahannan5, Shubham Pant6, David R Spigel7, Nataliya V Uboha8,9, Paul E Oberstein10, Anwaar Saeed11, Brandon Beagle12, Ji Yun Kim12, Ning Wang12, Ben Weeder12, Shravani Shitole12, Karim Mrouj12, Jennifer R Scott12, Lisa G Ensign13, Daniel M DiRenzo12, Matthew J Walters12, Wilson Wu12, Angelo Kaplan12, Soonweng Cho12, Omar Kabbarah14, Eileen M O'Reilly15,16
1Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. zwainberg@mednet.ucla.edu.
2Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
3Department of Gastrointestinal Medical Oncology, Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
4Department of Medical Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA.
5Hematology-Oncology Section, Department of Internal Medicine, Stephenson Cancer Center, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
6Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
7Oncology Department, Sarah Cannon Research Institute, Nashville, TN, USA.
8Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin, Madison, WI, USA.
9Carbone Cancer Center, Madison, WI, USA.
10Department of Medicine, Division of Hematology & Medical Oncology, NYU Langone Health, New York, NY, USA.
11Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
12Arcus Biosciences, Inc., Hayward, CA, USA.
13Medidata Solutions, Inc., a Dassault Systèmes company, New York, NY, USA.
14Arcus Biosciences, Inc., Hayward, CA, USA. okabbarah@arcusbio.com.
15Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. oreillye@mskcc.org.
16Department of Medicine, Weill Cornell Medical College, New York, NY, USA. oreillye@mskcc.org.
PubMed PMC DOI PDF

Abstract

Quemliclustat potently inhibits CD73, a key enzyme producing immunosuppressive adenosine. In a phase 1b trial (ARC-8), we evaluated safety and efficacy of quemliclustat combined with gemcitabine/nab-paclitaxel (G/nP) with or without zimberelimab (anti-programmed cell death protein 1 (PD-1)) in first-line metastatic pancreatic ductal adenocarcinoma (PDAC). During the dose-escalation phase, 22 patie…

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