2. Academic Validation
  3. Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors

Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors

  • Clin Cancer Res. 2017 Sep 15;23(18):5349-5357. doi: 10.1158/1078-0432.CCR-17-1243.
Anthony W Tolcher 1,  Mario Sznol 2,  Siwen Hu-Lieskovan 3,  Kyriakos P Papadopoulos 4,  Amita Patnaik 4,  Drew W Rasco 4,  Donna Di Gravio 5,  Bo Huang 6,  Dhiraj Gambhire 7,  Ying Chen 8,  Aron D Thall 8,  Nuzhat Pathan 8,  Emmett V Schmidt 9,  Laura Q M Chow 10
Affiliations

Affiliations

  • 1 START Center for Cancer Care, San Antonio, Texas. atolcher@start.stoh.com.
  • 2 Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut.
  • 3 David Geffen School of Medicine at UCLA, Los Angeles, California.
  • 4 START Center for Cancer Care, San Antonio, Texas.
  • 5 Pfizer Oncology, Collegeville, Pennsylvania.
  • 6 Pfizer Oncology, Groton, Connecticut.
  • 7 Pfizer Oncology, New York, New York.
  • 8 Pfizer Oncology, La Jolla, California.
  • 9 Merck & Co., Inc., Kenilworth, New Jersey.
  • 10 University of Washington, Seattle, Washington.
PMID: 28634283 DOI: 10.1158/1078-0432.CCR-17-1243
Abstract

Purpose: This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors.Experimental Design: Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event continual reassessment method.Results: Twenty-three patients received combination treatment with no dose-limiting toxicities. Treatment-emergent adverse events were mostly grades 1 to 2, without any treatment-related discontinuations. Six patients (26.1%) had confirmed complete or partial responses. Pharmacokinetics and immunogenicity of utomilumab and pembrolizumab were similar when administered alone or in combination. A trend toward higher levels of activated memory/effector peripheral blood CD8+ T cells was observed in responders versus nonresponders.Conclusions: The safety, tolerability, and clinical activity demonstrated by utomilumab in combination with pembrolizumab support further investigation in patients with advanced solid tumors. Clin Cancer Res; 23(18); 5349-57. ©2017 AACRSee related commentary by Pérez-Ruiz et al., p. 5326.

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