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Ref Type Journal Article
PMID (29549159)
Authors Segal NH, He AR, Doi T, Levy R, Bhatia S, Pishvaian MJ, Cesari R, Chen Y, Davis CB, Huang B, Thall AD, Gopal AK
Title Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 24
Issue 8
Date 2018 Apr 15
URL
Abstract Text Purpose: Utomilumab (PF-05082566) is an agonistic mAb that engages the immune costimulatory molecule 4-1BB/CD137. In this first-in-human, phase I, open-label, multicenter, multiple-dose study (NCT01307267) we evaluated safety, tolerability, pharmacokinetics, preliminary clinical activity, and pharmacodynamics of single-agent utomilumab in patients with advanced malignancies.Experimental Design: Dose escalation was based on a standard 3+3 design for doses of utomilumab from 0.006 to 0.3 mg/kg every 4 weeks and a time-to-event continual reassessment method for utomilumab 0.6 to 10 mg/kg every 4 weeks. The primary study endpoint was dose-limiting toxicity (DLT) in the first two cycles.Results: Utomilumab demonstrated a well-tolerated safety profile (N = 55). None of the patients experienced a DLT at the dose levels evaluated. The most common treatment-related adverse events were fatigue, pyrexia, decreased appetite, dizziness, and rash (<10% of patients). Only one (1.8%) patient experienced a grade 3-4 treatment-related adverse event (fatigue), and no clinically relevant elevations in transaminases were noted. Utomilumab demonstrated linear pharmacokinetics at doses ranging from 0.006 to 10 mg/kg, with similar safety and pharmacokinetics in anti-drug antibody (ADA)-negative and ADA-positive patients. The overall objective response rate was 3.8% (95% CI, 0.5%-13.0%) in patients with solid tumors and 13.3% in patients with Merkel cell carcinoma, including a complete response and a partial response. Circulating biomarkers support 4-1BB/CD137 engagement by utomilumab and suggest that circulating lymphocyte levels may influence probability of clinical benefit.Conclusions: The favorable safety profile and preliminary antitumor activity demonstrated by utomilumab warrant further evaluation in patients with advanced malignancies. Clin Cancer Res; 24(8); 1816-23. ©2018 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown Merkel cell carcinoma not applicable Utomilumab Phase I Actionable In a Phase I trial, Utomilumab (PF-05082566) treatment resulted in an overall objective response rate of 13.3% (2/15, 1 complete response, 1 partial response) in patients with Merkel cell carcinoma (PMID: 29549159; NCT01307267). 29549159
Unknown unknown Advanced Solid Tumor not applicable Utomilumab Phase I Actionable In a Phase I trial, Utomilumab (PF-05082566) treatment resulted in an overall objective response rate of 3.8% (2/53), a median progression-free survival of 1.7 months, and a median overall survival of 11.2 months in patients with advanced solid tumors (PMID: 29549159; NCT01307267). 29549159
Unknown unknown colorectal cancer no benefit Utomilumab Phase I Actionable In a Phase I trial, Utomilumab (PF-05082566) treatment resulted in no overall objective response (0/12) in patients with colorectal cancer (PMID: 29549159; NCT01307267). 29549159