BridgeBio collaborates with Bristol Myers Squibb

BridgeBio Pharma has entered a clinical collaboration with Bristol Myers Squibb to evaluate the combination of BBP-398, a potentially best-in-class SHP2 inhibitor, with OPDIVO (nivolumab) in patients with advanced solid tumours with KRAS mutations with the hope of providing an effective new treatment option for patients with difficult-to-treat cancers. 

The collaboration will also include the initiation of a Phase I/II study to evaluate the safety and preliminary efficacy of BBP-398 in combination with both OPDIVO as doublet therapy, and OPDIVO plus a KRASG12C inhibitor as triplet therapy in non-small cell lung cancer (NSCLC) with KRAS mutations, as first- and second-line treatment options.  

SHP2 is a protein-tyrosine phosphatase that links growth factor, cytokine and integrin signaling with the downstream RAS/ERK MAPK pathway to regulate cellular proliferation and survival. Overactivity of the SHP2 pathway, often driven by distinct genetic mutations, is a critical contributor to many forms of cancer, and is a mechanism of resistance to several targeted therapies. 

“Cancers that are driven by hyperactive MAPK signaling, including certain RAS mutations such as KRASG12C, may be sensitive to SHP2 inhibition,” said Frank McCormick, Chairman of Oncology at BridgeBio. “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.” 

KRAS mutations occur in approximately 27% of NSCLC cases and approximately 17% of malignant solid tumours. Combination of anti-PD-1 treatment with BBP-398, and other targeted therapies, could be promising for patients with KRAS mutations. 

“A priority of ours is to develop innovative medicines that target tumour intrinsic mechanisms including the MAPK pathway,” said Emma Lees, Senior Vice President of Oncology Research at Bristol Myers Squibb. “We look forward to beginning the clinical exploration of the mechanistic rationale and therapeutic benefit from combining robust MAPK pathway inhibition and PD-1 blockade in KRAS mutant NSCLC.” 

Image credit: National Cancer Institute

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