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

Gareth P. Gregory, Shaji Kumar, Ding Wang, Daruka Mahadevan, Patricia Walker, Nina Wagner-Johnston, Carolina Escobar, Rajat Bannerji, Divaya Bhutani, Julie Chang, Francisco J. Hernandez-Ilizaliturri, Andreas Klein, John M. Pagel, Witold Rybka, Andrew J. Yee, Anne Mohrbacher, Mo Huang, Mohammed Farooqui, Patricia Marinello, Hang Quach

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)1232-1242
Number of pages11
JournalBlood Advances
Volume6
Issue number4
DOIs
StatePublished - Feb 22 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology

Fingerprint

Dive into the research topics of 'Pembrolizumab plus dinaciclib in patients with hematologic malignancies: the phase 1b KEYNOTE-155 study'. Together they form a unique fingerprint.

Cite this