Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma

N. Yamazaki, H. Uhara, S. Fukushima, H. Uchi, N. Shibagaki, Y. Kiyohara, A. Tsutsumida, K. Namikawa, R. Okuyama, Y. Otsuka, T. Tokudome

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Purpose: Ipilimumab (IPI), a monoclonal antibody against immune-checkpoint receptor cytotoxic T lymphocyte antigen-4, is designed to enhance antitumor T cell function. IPI 10 mg/kg plus dacarbazine (DTIC) significantly improved overall survival in a phase 3 study involving predominantly Caucasian patients, with an adverse event (AE) profile similar to that of IPI monotherapy. We conducted a single-arm, phase 2 study to evaluate the safety and efficacy of IPI plus DTIC in Japanese patients. Methods: Previously untreated patients with unresectable stage III or IV melanoma received IPI 10 mg/kg plus DTIC 850 mg/m2 every 3 weeks for four doses (q3w × 4), followed by DTIC q3w × 4 and then IPI every 12 weeks until disease progression or intolerable toxicity. Results: All 15 treated patients reported drug-related AEs, the most common of which were increases in alanine aminotransferase (n = 12, 80 %) and aspartate aminotransferase (n = 11, 73 %). Treatment-related serious AEs were reported in 11 (73 %) patients. Nine patients (60 %) discontinued treatment due to drug-related toxicities. Immune-related AEs (irAEs) were reported in 14 patients (93 %). The most frequent irAEs were liver (n = 12, 80 %) and skin (n = 10, 67 %) toxicities. Five deaths were reported; all were caused by progressive disease. Efficacy evaluation showed one complete response, one partial response and four patients with stable disease. Best overall response rate was 13 % (2/15), and the disease control rate was 40 % (6/15). The study was terminated early due to frequent, high-grade liver toxicities. Conclusions: IPI 10 mg/kg plus DTIC 850 mg/m2 was not considered tolerable in the Japanese patient population. ClinicalTrials.gov identifier: NCT01681212.

Original languageEnglish
Pages (from-to)969-975
Number of pages7
JournalCancer chemotherapy and pharmacology
Volume76
Issue number5
DOIs
Publication statusPublished - Nov 1 2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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