1075TiP - KEYNOTE-029: Phase 1/2 study of MK-3475 in combination with pegylated interferon alfa-2b (PEG-IFN) or ipilimumab (IPI) in patients (Pts) with advan...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Renal Cell Cancer
Cancer Immunology and Immunotherapy
Melanoma and other Skin Tumours
Presenter Toni Choueiri
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors T. Choueiri1, A. Ribas2, F.S. Hodi3, J. Thompson4, W. Hwu5, A. Tosolini6, R. Iannone7, Z. Yang8, C. Gause9, R. Perini10, M.B. Atkins11
  • 1Medical Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, 02215 - BOSTON/US
  • 2Medical Oncology/hematology, UCLA, Los Angeles/US
  • 3Medical Oncology, Dana-Farber Cancer Institute, Boston/US
  • 4Medical L Oncology, Seattle Cancer Care Alliance, Seattle/US
  • 5Department Of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 6Oncology Clinical Research, Merck Research Laboratories, North Wales/US
  • 7Clinical Oncology Research, Merck & Co., Inc., North Wales/US
  • 8Bards, Merck & Co., Inc., North Wales/US
  • 9Late Development Statistics, Bard, Merck Sharp & Dohme Corp, North Wales/US
  • 10Oncology, Merck & Co., Inc., North Wales/US
  • 11Oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington DC/US

Abstract

Background

The interaction between programmed cell death protein 1 (PD-1) and its ligands PD-L1 and PD-L2 permits evasion of antitumor immune responses. PD-l inhibition has been shown to possess significant antitumor activity in patients with advanced MEL and RCC. Preclinical data suggest that adding PEG-IFN or IPI may increase the antitumor activity of PD-1 inhibitors. Clinically, IPI + the PD-1 antibody nivolumab has shown a greater response rate than nivolumab alone in pts with MEL. MK-3475 is a potent, highly selective, humanized IgG4/kappa, anti-PD-1 monoclonal antibody designed to block the interaction between PD-1 and its ligands.

Trial design

This is an open-label, multicenter, phase 1/2 study of MK-3475 in combination with PEG-IFN or IPI for pts with advanced MEL or RCC. Phase 1 is a dose escalation study designed to determine the maximum tolerated/administered dose and/or recommended phase 2 dose of MK-3475 + PEG-IFN and MK-3475 + IPI. Using a modified 3 + 3 design followed by a toxicity probability interval for dose confirmation, 3-14 pts per dose level will be enrolled sequentially at escalating/de-escalating MK-3475 doses (2 mg/kg intravenously [IV] 3 times/wk [Q3W] or 10 mg/kg Q2W) in combination with PEG-IFN (subcutaneous 1, 2, or 3 µg/kg/wk) or IPI (4 IV doses of 1 mg/kg Q3W). If dose levels are open for both PEG-IFN and IPI, pts will be randomized between the combinations. Pending phase 1 results, a randomized phase 2 study designed to evaluate the efficacy of combination therapy will be initiated. Up to 150 pts with MEL will be randomized 1:1:1 to MK-3475 + PEG-IFN, MK-3475 + IPI, or MK-3475 alone. Treatment will continue until progression, intolerable toxicity, or 24 mo of MK-3475. Primary endpoint is progression-free survival. Secondary endpoints include objective response rate, overall survival, and safety. Response will be evaluated by investigator by RECIST v1.1 at wk 12, every 6 wk thereafter until wk 30, and then every 12 wk. Adverse events will be monitored and graded according to NCI CTCAE v4.0. Phase 1 pt enrollment is ongoing.

Disclosure

T.K. Choueiri: Advisory board for Pfizer, GSK, Novartis, Aveo. Research funding from Pfizer (institutional) A. Ribas: Advisory board for Merck; F.S. Hodi: Nonpaid role on advisory board for Merck. Research support to institution from Merck; W. Hwu: Advisory board member, Merck. Corporate-sponsored research, Merck; A. Tosolini: Full-time employee of Merck Sharp & Dohme with stock ownership; R. Iannone: Full-time employee of Merck & Co., Inc., with stock ownership; Z. Yang: Full-time employee of Merck & Co., Inc., with stock ownership; C. Gause: Full-time employee of Merck Sharp & Dohme with stock ownership; R. Perini: Full-time employee of Merck & Co., Inc., with stock ownership; M.B. Atkins: Advisory board for BMS, Merck, Genentech. All other authors have declared no conflicts of interest.