Phase II Trial of Tremelimumab (CP-675,206) in Patients with Advanced Refractory or Relapsed Melanoma

• Published in: Clinical cancer research Vol. 16; no. 3; pp. 1042 - 1048
• Main Authors: KIRKWOOD, John M, LORIGAN, Paul, HERSEY, Peter, HAUSCHILD, Axel, ROBERT, Caroline, MCDERMOTT, David, MARSHALL, Margaret A, GOMEZ-NAVARRO, Jesus, LIANG, Jane Q, BULANHAGUI, Cecile A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-02-2010
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; anti-CTLA4 monoclonal antibody; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antineoplastic agents; Biological and medical sciences; Dermatology; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Humans; Male; Medical sciences; melanoma; Melanoma - drug therapy; Melanoma - pathology; Middle Aged; Pharmacology. Drug treatments; Recurrence; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Tumors of the skin and soft tissue. Premalignant lesions; Human; Tremelimumab; Relapse; Treatment resistance; Phase II trial; Malignant melanoma; Patient; Advanced stage; Malignant tumor; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-2033

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 ≤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 ≥170 days since enrollment, suggesting
a potential role for tremelimumab in melanoma. Clin Cancer Res; 16(3); 1042–8