Investigational New Drugs

, Volume 29, Issue 3, pp 489–498

A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma

  • Evan M. Hersh
  • Steven J. O’Day
  • John Powderly
  • Khuda D. Khan
  • Anna C. Pavlick
  • Lee D. Cranmer
  • Wolfram E. Samlowski
  • Geoffrey M. Nichol
  • Michael J. Yellin
  • Jeffrey S. Weber
PHASE II STUDIES

DOI: 10.1007/s10637-009-9376-8

Cite this article as:
Hersh, E.M., O’Day, S.J., Powderly, J. et al. Invest New Drugs (2011) 29: 489. doi:10.1007/s10637-009-9376-8

Summary

Objective: Ipilimumab is a fully human, anti–cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody that has demonstrated antitumor activity in advanced melanoma. We evaluated the safety and efficacy of ipilimumab alone and in combination with dacarbazine (DTIC) in patients with unresectable, metastatic melanoma. Methods: Chemotherapy-naïve patients were randomized in this multicenter, phase II study to receive ipilimumab at 3 mg/kg every 4 weeks for four doses either alone or with up to six 5-day courses of DTIC at 250 mg/m2/day. The primary efficacy endpoint was objective response rate. Results: Seventy-two patients were treated per-protocol (ipilimumab plus DTIC, n = 35; ipilimumab, n = 37). The objective response rate was 14.3% (95% CI, 4.8–30.3) with ipilimumab plus DTIC and was 5.4% (95% CI, 0.7–18.2) with ipilimumab alone. At a median follow-up of 20.9 and 16.4 months for ipilimumab plus DTIC (n = 32) and ipilimumab alone (n = 32), respectively, median overall survival was 14.3 months (95% CI, 10.2–18.8) and 11.4 months (95% CI, 6.1–15.6); 12-month, 24-month, and 36-month survival rates were 62%, 24% and 20% for the ipilimumab plus DTIC group and were 45%, 21% and 9% for the ipilimumab alone group, respectively. Immune-related adverse events were, in general, medically manageable and occurred in 65.7% of patients in the combination group versus 53.8% in the monotherapy group, with 17.1% and 7.7% ≥grade 3, respectively. Conclusion: Ipilimumab therapy resulted in clinically meaningful responses in advanced melanoma patients, and the results support further investigations of ipilimumab in combination with DTIC.

Keywords

Metastatic melanomaIpilimumabCTLA-4Immune therapyDacarbazine

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Evan M. Hersh
    • 1
  • Steven J. O’Day
    • 2
  • John Powderly
    • 3
  • Khuda D. Khan
    • 4
    • 5
  • Anna C. Pavlick
    • 6
  • Lee D. Cranmer
    • 1
  • Wolfram E. Samlowski
    • 7
  • Geoffrey M. Nichol
    • 8
  • Michael J. Yellin
    • 8
  • Jeffrey S. Weber
    • 9
  1. 1.Arizona Cancer CenterUniversity of ArizonaTucsonUSA
  2. 2.The Angeles Clinic and Research InstituteSanta MonicaUSA
  3. 3.Carolina Bio-Oncology InstituteCancer Therapy & Research CenterHuntersvilleUSA
  4. 4.St. Francis Hospital & Health CentersIndianapolisUSA
  5. 5.Elizabethtown Hematology & OncologyElizabethtownUSA
  6. 6.New York University Medical CenterNew YorkUSA
  7. 7.Nevada Cancer InstituteOne Breakthrough WayLas VegasUSA
  8. 8.Medarex, IncPrincetonUSA
  9. 9.H. Lee Moffitt Cancer Center and Research InstituteTampaUSA