Bristol-Myers Squibb (BMS) and Five Prime Therapeutics said today they will launch a Phase Ia/Ib study to assess the safety, tolerability, and preliminary efficacy of combining the pharma giant’s Opdivo (nivolumab) with the biotech’s monoclonal antibody FPA008 in six types of tumors.
Five Prime will generate $30 million-plus from the exclusive clinical collaboration, intended to study the cancer combination therapy for patients with non-small cell lung cancer (NSCLC), melanoma, head and neck cancer, pancreatic cancer, colorectal cancer, and malignant glioma.
The collaboration is the companies’ second in cancer and expands a cancer-treatment alliance between the companies launched in March. Back then, BMS agreed to use Five Prime Therapeutics’ target protein discovery platform to discover, develop and commercialize new immuno-oncology therapies for two undisclosed immune checkpoint pathways. That deal could be worth as much as $350.5 million to Five Prime.
“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,” Michael Giordano, BMS’ svp and head of development, oncology, said in a statement.
Today, the companies said, BMS will make a one-time payment of $30 million to Five Prime toward the cancer combo study, as well as fund study costs. Five Prime agreed in return to conduct the clinical trial, which is expected to begin in 2015.
The trial will assess Opdivo, BMS’ programmed death-1 (PD-1) immune checkpoint inhibitor, with FPA008, Five Prime's monoclonal antibody designed to inhibit colony stimulating factor-1 receptor (CSF1R).
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. BMS will have a time-limited right of first refusal subject to certain conditions if Five Prime wishes to seek a partner for FPA008, the companies said.
Opdivo is approved in Japan for the treatment of patients with unresectable melanoma. Opdivo is being developed in multiple tumor types in more than 50 clinical trials—as monotherapy or in combination with other therapies—in which more than 7,000 patients have been enrolled worldwide. Among these are several potentially registrational trials in NSCLC, melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and non-Hodgkin lymphoma (NHL).
In April, the company 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. A month later, the FDA granted Opdivo its Breakthrough Therapy Designation for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab. And on July 4, On July 4, Ono Pharmaceutical won manufacturing and marketing approval in Japan for Opdivo, making the drug the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world.
On September 26, the FDA accepted for priority review the Biologics License Application for Opdivo in previously treated advanced melanoma, with a Prescription Drug User Fee Act (PDUFA) decision date goal of March 30, 2015. The FDA also granted Opdivo Breakthrough Therapy status for that 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.
The compound has enjoyed FDA’s Fast Track designation in NSCLC, melanoma and RCC since 2012.
FPA008, a compound developed 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, the companies said.
FPA008 is designed to work by blocking the activation and survival of monocytes and macrophages. Inhibition of CSF1R in inflamed RA joints in turn 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, according to Five Prime.