Bristol Myers Squibb (BMS) will work with commercial-stage biopharmaceutical company BridgeBio Pharma to evaluate a study combining Opdivo (nivolumab) and BBP-398 (an SHP2 inhibitor). The study is designed to test the effectiveness and safety of the dual treatment in patients with advanced solid non-small cell lung cancer (NSCLC).
"Cancers that are driven by hyperactive MAPK signaling, including certain RAS mutations such as KRASG12C, may be sensitive to SHP2 inhibition," said Frank McCormick, BridgeBio’s chairman of oncology. "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."
Additionally, the collaboration also will include initiation of a Phase I/II study to evaluate the safety and preliminary efficacy of the SHP2 in combination with Opdivo as a doublet therapy, and Opdivo plus a KRASG12C inhibitor as triplet therapy in NSCLC with KRAS mutations, used as first- and second-line treatment options. According to the parties of the non-exclusive partnership, BMS will provide the nivolumab, and BridgeBio will act as sponsor of the clinical study; both will share the cost of clinical development activities.
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. According to BridgeBio, overactivity of the SHP2 pathway (frequently driven by distinct genetic mutations) is a critical contributor to many forms of cancer and is a mechanism of resistance to several targeted therapies.
"A priority of ours is to develop innovative medicines that target tumor intrinsic mechanisms including the MAPK pathway," said Emma Lees, BMS senior vice president of oncology research for BMS. "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."
"We are pleased to collaborate with Bristol Myers Squibb and advance BridgeBio's larger strategy to fully interrogate BBP-398, a potentially best-in-class SHP2 inhibitor, as an ideal combination agent for certain cancer patients given its profile and potential for once-daily dosing," said Eli Wallace, chief scientific officer of oncology at BridgeBio. "By partnering with one of the strongest oncology players in the industry, we hope to provide a new therapeutic approach to cancer patients in need."
BridgeBio is currently advancing its Phase I clinical trial in patients with solid tumors driven by mutations in the MAPK signaling pathway, including RAS and receptor tyrosine kinase genes.