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

  • PHASE II STUDIES
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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.

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Acknowledgments

The authors thank Steven A. Fischkoff (currently at Palatin Technologies, Cranbury, NJ) for technical assistance and Georgia Brockway for assistance in preparing and reviewing the data. Writing and editorial support was provided by StemScientific, funded by Bristol-Myers Squibb Co.

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Author notes

  1. Khuda D. Khan

    Present address: Elizabethtown Hematology & Oncology, 1107 Woodland Drive, Elizabethtown, KY, 42701, USA

Authors and Affiliations

  1. Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ, 85724, USA

    Evan M. Hersh & Lee D. Cranmer

  2. The Angeles Clinic and Research Institute, 2001 Santa Monica Blvd, Suite 560W, Santa Monica, CA, 90404, USA

    Steven J. O’Day

  3. Carolina Bio-Oncology Institute, Cancer Therapy & Research Center, 9801 W. Kincey Ave, Suite 145, Huntersville, NC, 28078, USA

    John Powderly

  4. St. Francis Hospital & Health Centers, 8111 S. Emerson Ave, Indianapolis, IN, 46237, USA

    Khuda D. Khan

  5. New York University Medical Center, 160 East 34th Street, New York, NY, 10016, USA

    Anna C. Pavlick

  6. Nevada Cancer Institute, One Breakthrough Way, Las Vegas, NV, 89135, USA

    Wolfram E. Samlowski

  7. Medarex, Inc, 707 State Road, Princeton, NJ, 08540, USA

    Geoffrey M. Nichol & Michael J. Yellin

  8. H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA

    Jeffrey S. Weber

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  1. Evan M. Hersh
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Correspondence to Evan M. Hersh.

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Hersh, E.M., O’Day, S.J., Powderly, J. et al. A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma. Invest New Drugs 29, 489–498 (2011). https://doi.org/10.1007/s10637-009-9376-8

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  • DOI: https://doi.org/10.1007/s10637-009-9376-8

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