Bristol-Myers Squibb and Five Prime Therapeutics, Inc., a biopharmaceutical company based in South San Francisco, California, have entered into an exclusive clinical collaboration agreement to evaluate the safety, tolerability, and preliminary efficacy of combining Opdivo (nivolumab), Bristol-Myers Squibb's investigational PD-1 (programmed death-1) immune checkpoint inhibitor, with FPA008, Five Prime's monoclonal antibody that inhibits colony stimulating factor-1 receptor (CSF1R).

The Phase Ia/IIb study will evaluate the combination of Opdivo and FPA008 as a potential treatment option for patients with non-small cell lung cancer (NSCLC), melanoma, head and neck cancer, pancreatic cancer, colorectal cancer, and malignant glioma. Bristol-Myers Squibb has proposed the name Opdivo, which, if approved by health authorities, will serve as the trademark for nivolumab.

Under the terms of this agreement, Bristol-Myers Squibb will make a one-time payment of $30 million to Five Prime and will be responsible for study costs. Five Prime will conduct the clinical trial, which is expected to begin in 2015. The agreement provides for exclusivity with respect to the development, with a collaborative partner, of combination regimens of anti-PD-1/PDL1 antagonists together with an anti-CSF1R antagonist. Bristol-Myers Squibb will have a time-limited right of first refusal subject to certain conditions if Five Prime wishes to seek a partner for FPA008.

Opdivo and FPA008 are part of a new class of cancer treatments known as immunotherapies that are designed to harness the body's own immune system to fight cancer. Opdivo is approved in Japan for the treatment of patients with unresectable melanoma and is being developed in multiple tumor types in more than 50 clinical trials, including as treatments for NSCLC, melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma, and non-Hodgkin lymphoma (NHL). FPA008, in development as a potential treatment for rheumatoid arthritis (RA) and solid tumors, has initiated dosing for a Phase I clinical trial in RA. Preclinical data suggest that combining antibodies targeting PD-1 and CSF1R may lead to an enhanced anti-tumor immune response compared to either approach alone in treating cancer.

In 2012, the US Food and Drug Administration granted Fast Track designation for Opdivo in NSCLC, melanoma, and RCC. In April 2014, BMS initiated a rolling submission with the FDA for Opdivo in third-line pre-treated squamous cell NSCLC and expects to complete the submission by year-end. The FDA granted Opdivo Breakthrough Therapy Designation in May 2014 for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab. On July 4, 2014, Ono Pharmaceutical Co. announced that Opdivo received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma, making Opdivo the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. On September 26, 2014, Bristol-Myers Squibb announced that the FDA accepted for priority review the biologics license application for previously treated advanced melanoma, and the Prescription Drug User Fee Act goal date for a decision is March 30, 2015. The FDA also granted Opdivo Breakthrough Therapy status for this indication. In the European Union, the European Medicines Agency (EMA) has validated for review the Marketing Authorization Application (MAA) for Opdivo in advanced melanoma. The application has also been granted accelerated assessment by the EMA's Committee for Medicinal Products for Human Use. The EMA also validated for review the MAA for Opdivo in NSCLC.

FPA008, an antibody that inhibits colony stimulating factor-1 receptor (CSF1R), blocks the activation and survival of monocytes and macrophages. Inhibition of CSF1R in inflamed RA joints blocks the production of inflammatory cytokines by macrophages and inhibits osteoclasts, monocyte-lineage cells that can cause bone erosions and joint destruction. Inhibition of CSF1R in many cancers reduces the number of immunosuppressive tumor-associated macrophages (TAMs), thereby facilitating an immune response against tumors.

Source: Bristol-Myers Squibb