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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Authors | Anthony 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 |
Journal | Clinical 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 |
PMID | 28634283
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
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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
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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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