TY - JOUR
T1 - Pembrolizumab plus dinaciclib in patients with hematologic malignancies
T2 - the phase 1b KEYNOTE-155 study
AU - Gregory, Gareth P.
AU - Kumar, Shaji
AU - Wang, Ding
AU - Mahadevan, Daruka
AU - Walker, Patricia
AU - Wagner-Johnston, Nina
AU - Escobar, Carolina
AU - Bannerji, Rajat
AU - Bhutani, Divaya
AU - Chang, Julie
AU - Hernandez-Ilizaliturri, Francisco J.
AU - Klein, Andreas
AU - Pagel, John M.
AU - Rybka, Witold
AU - Yee, Andrew J.
AU - Mohrbacher, Anne
AU - Huang, Mo
AU - Farooqui, Mohammed
AU - Marinello, Patricia
AU - Quach, Hang
N1 - Funding Information:
This study was supported by research funding from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenil-worth, NJ, USA. No grant number is applicable.
Funding Information:
The authors thank the patients and their families and all investigators and site personnel. They also thank Jennifer Gwo (employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA) for her statistical expertise. Medical writing and editorial assistance were provided by Matthew Grzywacz of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Funding Information:
Conflict-of-interest disclosure: G.P.G. received honoraria from Roche; is a member of the advisory boards for Roche, Janssen, Novartis/Sandoz, and Gilead; and received research funding from BeiGene, Janssen, Merck, and AbbVie. S.K. received research funding for clinical trials to the institution for AbbVie, Amgen, Bristol Myers Squibb, Carsgen, Janssen, Kite, Merck, AstraZeneca, Novar-tis, Roche/Genentech, Takeda, and Tenebio; is a consultant/advisory board member (no personal payments) for AbbVie, Amgen, Bristol Myers Squibb, Janssen, Roche/Genentech, Takeda, Kite, AstraZeneca, and Bluebird Bio; and is a consultant/advisory board member (with personal payment) for Oncopeptides, Beigene, and Antengene. N.W.-J. is on advisory boards for Epizyme, Karyopharm, Seattle Genetics, Grunenthal, Regeneron, ADC Therapeutics, and Verastem. R.B. received clinical trial funding (to the institution) from AbbVie, Roche, Genentech, Regeneron, and Pharmacyclics and has a family member who is an employee of Sanofi-Pasteur. D.B. received research funding from and is an advisory board member for Sanofi Pharmaceuticals. F.J.H.-I. is a consultant for and received honoraria from AstraZeneca, Amgen, Pharmacyclics, Seattle Genetics, Kite Pharmaceuticals, Curio, Novartis, and Karyopharm. J.M.P. is
Publisher Copyright:
© 2022 by The American Society of Hematology.
PY - 2022/2/22
Y1 - 2022/2/22
N2 - 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 5 17; DLBCL, n 5 38; MM, n 5 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.
AB - 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 5 17; DLBCL, n 5 38; MM, n 5 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85125328675&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2021005872
DO - 10.1182/bloodadvances.2021005872
M3 - Article
C2 - 34972202
AN - SCOPUS:85125328675
SN - 2473-9529
VL - 6
SP - 1232
EP - 1242
JO - Blood advances
JF - Blood advances
IS - 4
ER -