Phase I/II trial of tremelimumab in patients with metastatic melanoma

Luis H. Camacho, Scott Antonia, Jeffrey Sosman, John M. Kirkwood, Thomas F. Gajewski, Bruce Redman, Dmitri Pavlov, Cecile Bulanhagui, Viviana A. Bozon, Jesus Gomez-Navarro, Antoni Ribas

Research output: Contribution to journalArticlepeer-review

277 Scopus citations


Purpose Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with tremelimumab (CP-675,206), a fully human anti-CTLA4 monoclonal antibody, was tolerated and demonstrated antitumor activity in a single dose, dose-escalation phase I trial in patients with solid tumors. This phase I/II trial was conducted to examine safety of multiple doses of tremelimumab, to further assess efficacy, and to identify an appropriate dosing regimen for further development. Patients and Methods Twenty-eight patients with metastatic melanoma received monthly intravenous infusions of tremelimumab at 3, 6, or 10 mg/kg for up to 1 year to determine recommended monthly phase II dose. During phase II, 89 patients received tremelimumab 10 mg/kg once every month or 15 mg/kg every 3 months. Results No dose-limiting toxicity was observed in phase I once every month dosing. In phase II, 8 (10%) of 84 response-assessable patients attained objective antitumor responses; best overall objective response was one complete response and three partial responses in each dosing regimen. Most responses were durable (range, 3 to 30+ months). Most frequent treatment-related adverse events (AEs) were diarrhea, rash, and pruritus. Frequency of grade 3/4 AEs was 13% in the 15 mg/kg every 3 months arm and 27% in the 10 mg/kg once every month. Serious AEs were also less frequent in the 15 mg/kg once every 3 months cohort (9% v 23% in 10 mg/kg arm). Conclusion Multiple infusions of tremelimumab were generally tolerable and demonstrated single-agent antitumor activity. Both phase II regimens generated durable tumor responses. Based on its more favorable safety profile, 15 mg/kg every 3 months was selected for further clinical testing.

Original languageEnglish (US)
Pages (from-to)1075-1081
Number of pages7
JournalJournal of Clinical Oncology
Issue number7
StatePublished - Mar 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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