Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors
2017; American Association for Cancer Research; Volume: 23; Issue: 18 Linguagem: Inglês
10.1158/1078-0432.ccr-17-1243
ISSN1557-3265
AutoresAnthony W. Tolcher, Mario Sznol, Siwen Hu‐Lieskovan, Kyriakos P. Papadopoulos, Amita Patnaik, Drew Rasco, Donna Di Gravio, Bo Huang, Dhiraj Gambhire, Ying Chen, Aron D. Thall, Nazima Pathan, Emmett V. Schmidt, Laura Q.M. Chow,
Tópico(s)Immunotherapy and Immune Responses
ResumoAbstract 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 AACR. See related commentary by Pérez-Ruiz et al., p. 5326
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