Bristol Myers Seeks Redeeming Combination for Struggling Checkpoint Inhibitor


California-based biopharmaceutical firm BridgeBio Pharma has announced a funding collaboration with Bristol Myers Squibb to evaluate a potential treatment for patients with difficult-to-treat cancers. 

Under the terms of the agreement, the companies will co-finance a clinical study that will test the combination of SHP2 inhibitor BBP-398 and OPDIVO (nivolumab) in treating patients with advanced solid tumors KRAS mutations. The collaboration will also be the start of the Phase 1 of 2 study to evaluate the preliminary efficacy and safety of BBP-398 with both OPDIVO as doublet therapy and OPDIVO plus a KRAS G12C inhibitor as a triplet therapy for non-small cell lung cancer (NSCLC). 

The collaboration is non-exclusive. BridgeBio will sponsor the trial, while Bristol Myers Squibb will be responsible for supplying nivolumab. The cost of clinical development for the combination trial will be shared between the two firms. 

“With this collaboration, we hope to better elucidate our SHP2 inhibitor’s ability to enhance immuno-oncology and other targeted therapies to potentially provide options for patients with difficult-to-treat cancers as quickly and safely as possible,” said Frank McCormick, Ph.D., the chairman of oncology at BridgeBio, in a statement. 

“Cancers that are driven by hyperactive MAPK signaling, including certain RAS mutations like KRAS G12C, might be sensitive to SHP2 inhibition,” added Dr. McCormick.

BridgeBio is currently in the advanced stages of its Phase 1 trial in patients with tumors driven by mutations in the MAPK signaling pathway. These include receptor tyrosine kinase and RAS genes. 

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In the same press release, Bristol Myers Squibb senior vice president for oncology research Emma Lees said it is their priority to develop new medications that will target tumor intrinsic mechanisms. KRAS mutations happen in around 27 percent of NSCLC cases and about 17 percent of malignant solid tumors. With that said, the combination of anti-PD-1 treatment with the SHP2 inhibitor and other similar therapies could bode well for the future of cancers with KRAS mutations. 

The collaboration comes on the heels of news that Bristol Myers Squibb withdrew OPDIVO for liver cancer around three months after the U.S. Food and Drug Administration decided not to push through with its approval for this indication. The FDA previously granted the drug accelerated clearance for second-line liver cancer but later decided against it in April after further tests failed to confirm its efficacy. The partnership with BridgeBio indicates that Bristol Myers Squibb remains optimistic about OPDIVO’s future for other indications. 

BBP-398 was developed through the joint efforts of BridgeBio and the Therapeutics Discovery division of The University of Texas MD Anderson Cancer Center. Previously, the company partnered with LianBio to develop and commercialize the component to address different solid tumors, including pancreatic and colorectal cancer, in China and other Asian markets.


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