Pembrolizumab plus dinaciclib in patients with hematologic malignancies: the phase 1b KEYNOTE-155 study

Blood Advances - Tập 6 - Trang 1232-1242 - 2022
Gareth P. Gregory1, Shaji Kumar2, Ding Wang3, Daruka Mahadevan4, Patricia Walker5, Nina Wagner-Johnston6, Carolina Escobar7, Rajat Bannerji8, Divaya Bhutani9, Julie Chang10, Francisco J. Hernandez-Ilizaliturri11, Andreas Klein12, John M. Pagel13, Witold Rybka14, Andrew J. Yee15, Anne Mohrbacher16, Mo Huang17, Mohammed Farooqui17, Patricia Marinello17, Hang Quach18
1Department of Hematology, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia
2Department of Hematology and Oncology, Mayo Clinic, Rochester, MN
3Department of Medical Oncology, Henry Ford Cancer Institute, Detroit, MI
4Division of Hematology/Medical Oncology, UT Health San Antonio, San Antonio, TX
5Department of Hematology, Peninsula Health and Peninsula Private Hospitals, Frankston, VIC, Australia
6Division of Oncology, Johns Hopkins Medical Institution, Baltimore, MD
7Department of Hematology and Oncology, Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas, TX
8Section of Hematologic Malignancies, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
9Department of Hematology and Oncology, Columbia University Medical Center, New York, NY
10Department of Hematology, University of Wisconsin Carbone Cancer Center, Madison, WI
11Medical Oncology, Roswell Park Cancer Institute, Buffalo, NY
12Department of Hematology and Oncology, Tufts Medical Center, Boston, MA
13Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer Institute, Seattle, WA
14Division of Hematology and Oncology, Penn State Cancer Institute, Hershey, PA
15Medical Oncology, Massachusetts General Hospital, Boston, MA
16Department of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, CA
17Department of Medical Oncology, Merck & Co., Inc., Kenilworth, NJ
18Department of Hematology, St. Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia

Tóm tắt

Abstract

Preclinical data demonstrated that combining an anti–programmed cell death 1 (PD-1) inhibitor with a cyclin-dependent kinase 9 (CDK9) inhibitor provided enhanced antitumor activity with no significant toxicities, suggesting this combination may be a potential therapeutic option. The multicohort, phase 1 KEYNOTE-155 study evaluated the safety and antitumor activity of the PD-1 inhibitor pembrolizumab plus the CDK9 inhibitor dinaciclib in patients with relapsed or refractory (rr) chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Patients enrolled were ≥18 years of age with a confirmed diagnosis of CLL, DLBCL, or MM. The study included 2 phases: a dose-evaluation phase to determine dose-limiting toxicities and a signal-detection phase. Patients received pembrolizumab 200 mg every 3 weeks plus dinaciclib 7 mg/m2 on day 1 and 10 mg/m2 on day 8 of cycle 1 and 14 mg/m2 on days 1 and 8 of cycles 2 and later. Primary endpoint was safety, and a key secondary endpoint was objective response rate (ORR). Seventy-two patients were enrolled and received ≥1 dose of study treatment (CLL, n = 17; DLBCL, n = 38; MM, n = 17). Pembrolizumab plus dinaciclib was generally well tolerated and produced no unexpected toxicities. The ORRs were 29.4% (5/17, rrCLL), 21.1% (8/38, rrDLBCL), and 0% (0/17, rrMM), respectively. At data cutoff, all 72 patients had discontinued treatment, 38 (52.8%) because of progressive disease. These findings demonstrate activity with combination pembrolizumab plus dinaciclib and suggest that a careful and comprehensive approach to explore anti–PD-1 and CDK9 inhibitor combinations is warranted. This trial was registered at www.clinicaltrials.gov as NCT02684617.


Tài liệu tham khảo

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Blood Advances

Tập 6

1232-1242

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