The PD-L1/PD-1 pathway may be an important mechanism of tumor immune escape in hematologic malignancies. In the multicohort, phase 1b KEYNOTE-013 study of pembrolizumab (pembro) in patients with hematologic malignancies, pembro was associated with a tolerable safety profile and a promising objective response rate (ORR, 40% [4/10]) in patients with rrPMBCL. In the phase 2 MC1485 study in patients with chronic lymphocytic leukemia (CLL) including RS, pembro showed promising preliminary efficacy (ORR, 43% [3/7]) in patients with rrRS. The open-label, multicenter, phase 2 KEYNOTE-170 study (NCT02576990) was designed to further evaluate the safety and efficacy of pembro in patients with rrPMBCL and rrRS.
Eligible patients must be aged ≥18 years and have either (1) diagnosis of rrPMBCL according to WHO 2008 criteria, failed to achieve a complete response (CR) or relapsed after autologous stem-cell transplantation (auto-SCT), or are ineligible for auto-SCT and have failed to respond or relapsed after ≥2 lines of prior treatment; or (2) pathologic diagnosis per local institutional review of rrRS that transformed from underlying CLL, have received at ≥1 prior therapy for rrRS, and have relapsed or refractory disease. Patients are to receive pembro 200 mg intravenously every 3 weeks for up to 35 cycles or until disease progression or unacceptable toxicity. In patients with rrRS, additional standard therapies to treat the underlying CLL may be added at the physician's discretion. Eligible patients who attain a CR as determined by the independent central imaging vendor may stop trial treatment and would be eligible for retreatment if they experience disease progression. Response is to be assessed every 12 weeks by independent central imaging vendor review based on International Working Group (IWG) response criteria. The primary end point is ORR by independent central imaging vendor according to IWG response criteria or IWG response criteria with special considerations for RS; secondary end points include PFS, OS, and safety and tolerability. Enrollment will continue until ∼106 patients have been enrolled.
Clinical trial identification
Legal entity responsible for the study
Merck & Co., Inc.
Merck & Co., Inc.
J-M. Michot: Advisory board member Bristol Myers Squibb. W. Ding: Corporate-sponsored research: Merck, research funding. A. Balakumaran, P. Marinello, S. Chlosta, Y. Zhang: Employee of Merck & Co, Inc. All other authors have declared no conflicts of interest.