After meeting with the US Food and Drug Administration (FDA), Medarex, Inc. and Bristol-Myers Squibb Company said, the companies will delay the Biologics License Application (BLA) submission for ipilimumab, an investigational immunotherapy for patients with advanced metastatic melanoma.

The FDA has requested additional overall survival (OS) data to further demonstrate the benefit of ipilimumab. Revised timelines are under development, but a BLA for ipilimumab will not be submitted to the FDA in 2008.

The randomised phase III trial evaluating the efficacy of ipilimumab in combination with dacarbazine versus dacarbazine alone in patients with untreated unresectable Stage III or Stage IV melanoma is ongoing under Special Protocol Assessment (SPA). The companies are engaged in discussions with the FDA to change the primary endpoint in this trial from progression free survival (PFS) to OS. A potential submission for melanoma would include survival data from patients in the phase II second-line studies and the randomised phase II first-line trial currently ongoing.

Bristol-Myers Squibb and Medarex remain committed to the development of ipilimumab. The companies also have ongoing phase II studies in hormone-refractory prostate cancer and lung cancer as well as a phase II study, to be initiated shortly, in adjuvant melanoma.

Ipilimumab is a fully human antibody that binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that plays a critical role in regulating natural immune responses. The absence or presence of CTLA-4 can augment or suppress the immune system's T-cell response in fighting disease. Ipilimumab is designed to block the activity of CTLA-4, thereby sustaining an active immune response in its attack on cancer cells.

Twelve abstracts evaluating ipilimumab in melanoma will be presented at the American Society of Clinical Oncology (ASCO) annual meeting this year. These include data from the three phase II trials evaluating ipilimumab in patients with advanced Stage III or Stage IV metastatic melanoma (Abstract #9010, 9021 and 9025). Ipilimumab is being developed through a joint partnership between Bristol-Myers Squibb and Medarex. Based on nonclinical and clinical studies showing that antibody blockade of CTLA-4 plays an important role in sustaining an active immune response to fight cancer, the companies are pursuing a broad clinical development programme with ipilimumab. More than 2,000 patients have been treated in clinical trials with ipilimumab as a monotherapy or in combination with other agents.