Bristol-Myers Squibb (BMS) has entered into a clinical development collaboration with, to evaluate Exelixis’ Cabometyx (cabozantinib), a small molecule inhibitor of receptor tyrosine kinases indicated for treating advance renal cell carcinoma (RCC), or kidney cancer, with BMS’ Opdivo (nivolumab), a programmed death-1 immune checkpoint inhibitor indicated for treating several cancers, either alone or in combination with Yervoy (ipilimumab), BMS anti-cancer agent indicated for treating metastatic melanoma. Opdivo, approved by the US Food and Drug Administration (FDA) in 2014, is a blockbuster drug for BMS with 2016 sales of $3.77 billion.

The clinical development program for the combination regimen of Opdivo and Cabometyx will be co-funded by the companies. The program is expected to include a Phase III pivotal trial in first-line RCC treatment, with additional trials planned in bladder cancer, hepatocellular carcinoma (HCC), and potentially other tumor types. The collaboration builds on previously published preclinical and clinical data that provide a scientific rationale for combining Cabometyx with immunotherapies.

Opdivo and Cabomyetyx have both received approval in the US and European Union for specific uses in previously treated renal cell carcinoma, and both compounds are the subject of ongoing, global Phase III pivotal trials in HCC.

Opdivo indications include use as a single agent for treating BRAF V600 mutation-positive unresectable or metastatic melanoma and BRAF V600 wild-type unresectable or metastatic melanoma; use in combination with Yervoy for treating unresectable or metastatic melanoma; treating metastatic non-small cell lung cancer; treating advanced RCC; treating classical Hodgkin lymphoma; treating recurrent or metastatic squamous cell carcinoma of the head and neck; and treating locally advanced or metastatic urothelial carcinoma.

Cabometyx is the tablet formulation of cabozantinib and is available in 20-mg, 40-mg, or 60-mg doses. The FDA approved Cabometyx tablets in April 2016 for treating patients with advanced RCC, and the European Commission approved it for use in the European Union, Norway, and Iceland in September 2016 for the same indication.

Other collaborations the companies formed for their respective products include BMS’ 2011 agreement with Ono Pharmaceutical, an Osaka, Japan-headquartered specialty pharmaceutical company, which expanded BMS’ territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea, and Taiwan. Under this agreement, Ono retained all rights to Opdivo at the time. In July 2014, BMS and Ono further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies, as single agents and in combination regimens, for cancer indications in Japan, South Korea, and Taiwan.

Exelixis holds agreements with Ipsen and Takeda. Under its February 2016 agreement with Ipsen, a Paris-headquartered pharmaceutical company, Exelixis granted Ipsen an exclusive license for the commercialization and further development of indications for cabozantinib, the active ingredient in Cabometyx, outside of the US, Canada, and Japan. This agreement was amended in December 2016 to include commercialization rights for Ipsen in Canada. Ipsen, Exelixis’ global partner for cabozantinib in all geographies outside the US and Japan, has opted in to participate in the Phase III pivotal trial in first-line RCC and will have access to the results to support potential future regulatory submissions. They may also participate in future studies at their choosing.

In its January 2017 agreement with Takeda, Exelixis granted Takeda an exclusive license for the commercialization and further development of cabozantinib indications in Japan. Takeda may also participate in these and future studies and have access to the results to support potential future regulatory submissions in Takeda’s territories, if the company opts into funding obligations under the respective collaboration agreements. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the US.

Source: Bristol-Myers Squibb