Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma.
AuthorsKirkwood, John M
Lorigan, Paul C
McDermott, David F
Marshall, Margaret A
Liang, Jane Q
Bulanhagui, Cecile A
AffiliationUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. email@example.com
MetadataShow full item record
AbstractPURPOSE: 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.
CitationPhase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma. 2010, 16 (3):1042-8 Clin Cancer Res
JournalClinical Cancer Research
- Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer.
- Authors: Chung KY, Gore I, Fong L, Venook A, Beck SB, Dorazio P, Criscitiello PJ, Healey DI, Huang B, Gomez-Navarro J, Saltz LB
- Issue date: 2010 Jul 20
- Phase II study of biweekly plitidepsin as second-line therapy in patients with advanced malignant melanoma.
- Authors: Eisen T, Thomas J, Miller WH Jr, Gore M, Wolter P, Kavan P, Martín JA, Lardelli P
- Issue date: 2009 Jun
- Modulation of lymphocyte regulation for cancer therapy: a phase II trial of tremelimumab in advanced gastric and esophageal adenocarcinoma.
- Authors: Ralph C, Elkord E, Burt DJ, O'Dwyer JF, Austin EB, Stern PL, Hawkins RE, Thistlethwaite FC
- Issue date: 2010 Mar 1
- Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.
- Authors: Ribas A, Kefford R, Marshall MA, Punt CJ, Haanen JB, Marmol M, Garbe C, Gogas H, Schachter J, Linette G, Lorigan P, Kendra KL, Maio M, Trefzer U, Smylie M, McArthur GA, Dreno B, Nathan PD, Mackiewicz J, Kirkwood JM, Gomez-Navarro J, Huang B, Pavlov D, Hauschild A
- Issue date: 2013 Feb 10
- Ctla-4 blockade confers lymphocyte resistance to regulatory T-cells in advanced melanoma: surrogate marker of efficacy of tremelimumab?
- Authors: Ménard C, Ghiringhelli F, Roux S, Chaput N, Mateus C, Grohmann U, Caillat-Zucman S, Zitvogel L, Robert C
- Issue date: 2008 Aug 15