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

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.
AuthorsAnthony W Tolcher, Mario Sznol, Siwen Hu-Lieskovan, Kyriakos P Papadopoulos, Amita Patnaik, Drew W Rasco, Donna Di Gravio, Bo Huang, Dhiraj Gambhire, Ying Chen, Aron D Thall, Nuzhat Pathan, Emmett V Schmidt, Laura Q M Chow
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 18 Pg. 5349-5357 (Sep 15 2017) ISSN: 1557-3265 [Electronic] United States
PMID28634283 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
Copyright©2017 American Association for Cancer Research.
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • utomilumab
  • pembrolizumab
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal (administration & dosage, pharmacokinetics)
  • Antibodies, Monoclonal, Humanized (administration & dosage, pharmacokinetics)
  • Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
  • Combined Modality Therapy
  • Diagnostic Imaging
  • Drug Monitoring
  • Female
  • Humans
  • Immunoglobulin G (administration & dosage)
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Neoplasms (diagnosis, drug therapy, metabolism, mortality)
  • Retreatment
  • T-Lymphocyte Subsets (drug effects, immunology, metabolism)
  • Treatment Outcome
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 (antagonists & inhibitors)

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