NEW YORK & SOUTH SAN FRANCISCO, Calif.—On Nov. 24, Bristol-Myers Squibb and Five Prime Therapeutics announced an exclusive clinical collaboration to evaluate the combination of investigational immunotherapies Opdivo (nivolumab) and FPA008 in six tumor types.
Under the agreement, they will work to evaluate the safety, tolerability and preliminary efficacy of combining Opdivo, 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 1a/1b 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.
Opdivo and FPA008 are both immunotherapies that are designed to harness the body’s own immune system to fight cancer, and Opdivo is already approved in Japan for the treatment of patients with unresectable melanoma—the compound is also being developed in multiple other tumor types in more than 50 clinical trials. FPA008, in development as a potential treatment for rheumatoid arthritis (RA) and solid tumors, has initiated dosing for a Phase 1 clinical trial in RA. Preclinical data suggest that combining antibodies targeting PD-1 and CSF1R may lead to an enhanced antitumor immune response compared to either approach alone in treating cancer.
“This collaboration supports our strategy to expand the clinical development of Opdivo, including novel combination regimens and across numerous tumor types,” said Michael Giordano, senior vice president, head of development, Oncology, Bristol-Myers Squibb. “We are excited to build upon our existing relationship with Five Prime Therapeutics in immuno-oncology, and explore the full potential of Opdivo and FPA008 in multiple tumor types.”
“We are pleased to establish a second collaboration with Bristol-Myers Squibb in the area of immuno-oncology,” said Dr. Lewis T. “Rusty” Williams, president and CEO of Five Prime. “Their vision aligns with our commitment to advancing promising immune-modulating targets, alone or in combination, to create next-generation immunotherapies for cancer patients. We look forward to initiating this study and expanding the development of FPA008 as a potential immunotherapy for these six types of cancer.”
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.
In 2012, the FDA granted Fast Track designation for Opdivo in NSCLC, melanoma and renal cell carcinoma. In April 2014, the company initiated a rolling submission with the FDA for Opdivo in third-line pretreated squamous cell NSCLC and expects to complete the submission by year’s 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 Sept. 26, 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, which inhibits 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, thereby facilitating an immune response against tumors.