Clinical study of MDX-010/MDX-1379 combination shows durable responses in patients with metastatic melanoma

Medarex, Inc. and Bristol-Myers Squibb Company announced today that complete or partial responses in seven of 56 patients with metastatic melanoma showed durability ranging from four months to the longest still ongoing at over 34 months, with five of the seven responses ongoing for more than two years.

These patients were treated in a Phase II clinical study with the investigational fully human anti-CTLA-4 antibody, MDX-010, in combination with MDX-1379, a gp100 melanoma vaccine. The Phase II clinical trial was conducted by Steven A. Rosenberg, M.D., Ph.D., Chief of Surgery at the National Cancer Institute, under a Cooperative Research and Development Agreement with Medarex. Results from the clinical trial were presented at the 96th Annual Meeting of the American Association of Cancer Research, April 16- 20, 2005, in Anaheim, CA.

The Phase II clinical trial evaluated two dose regimens of MDX-010 in combination with MDX-1379 in a total of 56 patients with metastatic melanoma. All patients had stage IV disease, Karnofsky performance status greater than or equal to 60, no previous MDX-010 treatment or gp100 vaccination, no evidence of autoimmune or immunodeficiency, and 3 weeks had elapsed since any previous systemic cancer therapy. Of the 56 patients, 29 patients (cohort 1) received 3.0 mg/kg intravenously over 90 minutes of MDX-010 and MDX-1379 every three weeks, and 27 patients (cohort 2) received an initial dose of 3.0 mg/kg intravenously over 90 minutes of MDX-010 and MDX-1379, followed by subsequent doses of 1.0 mg/kg of MDX-010 every three weeks. Data on the initial 14 patients in cohort 1 and the initial 24 patients in cohort 2 were previously presented at the 2003 annual meeting of the American Society of Clinical Oncology.

Four of the 29 patients treated in cohort 1 experienced complete or partial responses. Two patients experienced complete responses that are ongoing at over 30 and 31 months, respectively, and two additional patients experienced partial responses, with one response lasting four months and the other ongoing at over 34 months. In cohort 2, three of 27 patients experienced partial responses, with one partial response ongoing to six months and two partial responses ongoing at 25 and 26 months, respectively.

Grade III/IV adverse events were reported in nine of 29 patients in cohort 1 and five of 27 patients in cohort 2, with colitis (seven patients) and dermatitis (four patients) being the most frequently reported. All of the Grade III/IV events were normalized or managed with medical treatment involving hospitalization, intravenous hydration, steroids, or other medical management. The management of immune-mediated toxicities required strict attention to patient complaints and prompt diagnosis, as they could require surgery or potentially be lethal if not vigorously treated. Of the seven patients who experienced complete or partial responses in the Phase II clinical trial, Grade III/IV events were reported in all five patients with ongoing duration of response greater than or equal to 25 months; no Grade III/IV events were reported in the two patients who experienced partial responses of four and six months duration.

"We are encouraged by the duration of responses in this metastatic melanoma patient population and look forward to the results of the Phase III clinical trial and other trials that investigate the ability of MDX-010 to offer a new approach to treating cancer," said Donald L. Drakeman, President & CEO of Medarex.