Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma.
Authors
Kirkwood, John MLorigan, Paul C
Hersey, Peter
Hauschild, Axel
Robert, Caroline
McDermott, David F
Marshall, Margaret A
Gomez-Navarro, Jesus
Liang, Jane Q
Bulanhagui, Cecile A
Affiliation
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. kirkwoodjm@upmc.eduIssue Date
2010-02-01
Metadata
Show full item recordAbstract
PURPOSE: This phase II study assessed the antitumor activity of tremelimumab, a fully human, anti-CTL-associated antigen 4 monoclonal antibody, in patients with melanoma. EXPERIMENTAL DESIGN: Patients with refractory/relapsed melanoma received 15 mg/kg tremelimumab every 90 days. After 4 doses, patients with tumor response or stable disease were eligible to receive < or =4 additional doses. Primary endpoint was best overall tumor response assessed by an independent endpoint review committee, and secondary endpoints included duration of response, overall survival, progression-free survival, and safety. RESULTS: Of 251 patients enrolled, 246 (241 response-evaluable) received tremelimumab. Objective response rate was 6.6% (16 partial responses); duration of response was 8.9 to 29.8 months. Eight (50%) objective responses occurred in patients with stage IV M(1c) disease, and 11 (69%) were ongoing at last tumor assessment. Eight (3.3%) patients achieved responses in target lesions (Response Evaluation Criteria in Solid Tumors) despite progressive disease within the first cycle. All 8 survived for >20 months; 5 (63%) remained alive. Clinical benefit rate (overall response + stable disease) was 21% (16 partial responses and 35 stable disease), and median overall survival was 10.0 months. Progression-free survival at 6 months was 15%, and survival was 40.3% at 12 months and 22% at 24 months. Common treatment-related adverse events were generally mild to moderate, and grade 3/4 adverse events included diarrhea (n = 28, 11%), fatigue (n = 6, 2%), and colitis (n = 9, 4%). There were 2 (0.8%) treatment-related deaths. CONCLUSIONS: Tremelimumab showed an objective response rate of 6.6%, with all responses being durable > or =170 days since enrollment, suggesting a potential role for tremelimumab in melanoma.Citation
Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma. 2010, 16 (3):1042-8 Clin Cancer ResJournal
Clinical Cancer ResearchDOI
10.1158/1078-0432.CCR-09-2033PubMed ID
20086001Type
ArticleLanguage
enISSN
1078-0432ae974a485f413a2113503eed53cd6c53
10.1158/1078-0432.CCR-09-2033
Scopus Count
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