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BridgeBio, Amgen to Study SHP2 Inhibitor, Lumakras Combo in KRAS-Mutant Tumors

NEW YORK – BridgeBio Pharma and Amgen on Thursday said they will collaborate on a study of BridgeBio's SHP2 inhibitor BBP-398 combined with sotorasib (Amgen's Lumakras) in patients with advanced solid tumors driven by the KRAS G12C mutation.

The US Food and Drug Administration approved sotorasib last year for previously treated patients with advanced KRAS G12C-mutated non-small cell lung cancer. Since then, Amgen has reported results showing the drug has more limited efficacy in KRAS G12C-mutated colorectal cancer patients, raising questions about the drug's single-agent pan-tumor efficacy and spurring the drugmaker's interest in exploring combination therapy approaches.

For example, Amgen is conducting a randomized Phase III trial of sotorasib and its monoclonal antibody panitumumab (Vectibix) versus standard-of-care treatment in KRAS G12C-mutated colorectal cancer patients. The latest collaboration with BridgeBio represents another opportunity to study a combination treatment approach with sotorasib in a pan-tumor fashion.

BridgeBio will sponsor the Phase I/II trial of sotorasib and its SHP2 inhibitor BBP-398, which it developed in collaboration with MD Anderson Cancer Center's therapeutics discovery division.

"Overactivity of the MAPK pathway is a significant cause of many types of difficult-to-treat cancers, and by combining these two agents, we aim to reduce the oncogenic potential of tumor cells," Frank McCormick, chairman of oncology at BridgeBio, said in a statement. "Building on our collaborations with Bristol Myers Squibb and LianBio, we are excited to be working with Amgen on this new collaboration."

In 2021, BridgeBio partnered with BMS to study BBP-398 with nivolumab (BMS' Opdivo) in advanced solid tumors with KRAS mutations and with nivolumab plus a KRAS G12C inhibitor in KRAS-mutated NSCLC patients. In 2020, the company partnered with LianBio to develop and commercialize BBP-398 and other candidates in China.

The Palo Alto, California-based company also began a single-agent Phase I study in 2020 of BBP-398 in solid tumors harboring MAPK signaling pathway genetic mutations.

At the annual JP Morgan Healthcare Conference this week, BridgeBio discussed its own programs to develop a pan-KRAS inhibitor and a next-generation KRAS G12C inhibitor that could potentially overcome resistance to first-generation drugs.