53TiP - Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma: Randomized phase 3 KEYNOTE-204 study

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Pier Luigi Zinzani
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors P.L. Zinzani1, J. Kline2, R. Chen3, V. Ribrag4, G. Salles5, I. Matsumura6, Y. Zhu7, A. Ricart7, A. Balakumaran7, M. Fanale8
  • 1Oncology, Institute of Hematology “L. e A. Seràgnoli,” Università di Bologna, 40126 - Bologna/IT
  • 2Department Of Medicine, University of Chicago, Chicago/US
  • 3Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte/US
  • 4Oncology, Institut Gustave Roussy, Villejuif/FR
  • 5Hematologie, Centre Hospitalier, Lyon/FR
  • 6Division Of Hematology And Rheumatology Department, Kindai University, Osaka/JP
  • 7Oncology, Merck & Co., Inc., Kenilworth/US
  • 8Oncology, The University of Texas MD Anderson Cancer Center, Houston/US

Abstract

Aim/Background

Patients with classical Hodgkin lymphoma (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 demonstrated an objective response rate (ORR) of 65% in heavily pretreated patients with cHL.

Trial design

KEYNOTE-204 (NCT02684292) is a randomized, international, open-label phase 3 study designed to compare the efficacy and safety of pembrolizumab versus brentuximab vedotin (BV) in patients with R/R cHL. Key eligibility criteria include patients aged ≥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 chemotherapy-resistant disease (unable to achieve complete or partial remission to salvage chemotherapy), advanced age, or comorbidities, and have received ≥2 prior multiagent chemotherapy regimens that did not include BV. ∼300 patients will be randomized 1:1 to receive either pembrolizumab 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

ClinicalTrials.gov, NCT02684292

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Disclosure

R. Chen: Consulting Fees - Merck, Seattle Genetics, Genentech Membership on an entity\'s board of directors, speakers bureau, or its advisory committees - Seattle Genetics, Genentech, Millennium. V. Ribrag: Research Funding - ArgenX Membership on an entity\'s board of directors, speakers bureau, or its advisory committees - Gilead, Infinity, Pharmamar, BMS, Esai, Incyte, Nanostring. G. Salles: Research Funding and Honoraria - Gilead Consultancy, Research Funding and Honoraria - Roche/Genentech Consultancy and Honoraria - Janssen, Celgene, Amgen and Novartis Honoraria – Mundipharma. I. Matsumura: Ad board member - MDS Pharma and K.K. Pharma. Y. Zhu, A. Balakumaran: Employee of Merck & Co., Inc. A. Ricart: Employee of Merck & Co., Inc. Ownership interest (including stock options, but excluding indirect investments through mutual funds and the like) in a publicly traded company – Pfizer. M. Fanale: Research Funding - Merck Membership on an entity\'s board of directors, speakers bureau, or its advisory committees – Merck. All other authors have declared no conflicts of interest.