Patients with cHL who relapse after autologous stem-cell transplantation (auto-SCT) or are ineligible to proceed to transplantation have poor prognosis. The PD-1 ligands, PD-L1 and PD-L2, are frequently overexpressed in relapsed or refractory (R/R) cHL, and this is typically associated with chromosome 9p24.1 amplification. In the phase 1b KEYNOTE-013 study, PD-1 blockade with pembrolizumab (pembro) demonstrated an objective response rate (ORR) of 65% in heavily pretreated patients with cHL. KEYNOTE-204 (NCT02684292) is a randomized, international, open-label phase 3 study designed to compare the efficacy and safety of pembro vs brentuximab vedotin (BV) in patients with R/R cHL.
This study will enroll patients age ≥18 years with R/R cHL who (1) have failed to achieve a response or progressed after auto-SCT and have not received prior BV; or (2) are not auto-SCT candidates because of chemo-resistant disease (unable to achieve complete or partial remission to salvage chemotherapy), advanced age, or comorbidities, and have received ≥2 prior multi-agent chemotherapy regimens that did not include BV. ∼300 patients will be randomized 1:1 to receive either pembro 200 mg Q3W or BV 1.8 mg/kg Q3W for up to 35 cycles or until documented disease progression, unacceptable toxicity, or investigator decision. Response will be assessed every 12 weeks by PET/CT scans per Revised Response Criteria for Malignant Lymphoma from the International Working Group (IWG) by central imaging vendor review. Primary end points are PFS and OS; secondary end points are ORR and complete remission rate. The primary assessment of efficacy end points will be based on blinded independent central review according to the IWG criteria; secondary/exploratory analyses of efficacy end points will be conducted using investigator assessment. Exploratory end points include PK profile, duration of response, and comparison of ORR in patients with PD-L1–positive versus PD-L1–negative lymphoid tumors. Enrollment to KEYNOTE-204 is ongoing.
Clinical trial identification
Legal entity responsible for the study
Merck & Co., Inc.
Merck & Co., Inc.
Y. Zhu, A.D. Ricart, A. Balakumaran: Employee and stock ownership at Merck & Co, Inc. All other authors have declared no conflicts of interest.