BridgeBio and Amgen Announce Clinical Collaboration to Evaluate BBP-398 and LUMAKRAS® Combination Therapy for KRAS G12C-Mutated Advanced Solid Tumors

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Recently, BridgeBio and Amgen reached a non-exclusive clinical collaboration to evaluate the combination regimen of BBP-398 and the KRASG12C inhibitor Lumakras (sotorasib) for the treatment of patients with advanced solid tumors carrying the KRAS G12C mutation.

The Phase 1/2 study will include a dose-escalation phase, followed by dose expansion and optimization. The study aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of BBP-398 in combination with Lumakras. According to the non-exclusive collaboration terms, BridgeBio will sponsor the study, and Amgen will provide Lumakras globally.

Lumakras is the first KRAS-targeted therapy approved for marketing after nearly 40 years of research, receiving U.S. FDA approval in May 2021. The drug selectively and irreversibly inhibits KRAS proteins carrying the G12C mutation by locking the G12C-mutant KRAS protein in an inactive GDP-bound state, thereby specifically suppressing its pro-proliferative activity.

BBP-39 is a potent small-molecule inhibitor targeting SHP2. SHP2 is a protein tyrosine phosphatase that links growth factor, cytokine, and integrin signaling to the downstream RAS/ERK MAPK pathway, regulating cell proliferation and survival. In cancer patients with KRAS G12C mutations, the combination of BBP-398 + Lumakras has the potential to prevent tumorigenesis and hyperactive cell proliferation by combining SHP2 inhibition with KRASG12C inhibition.

Image Source: cancer.gov

Approximately 17% of malignant solid tumors exhibit KRAS mutations. BBP-398, as a monotherapy or in combination with other targeted therapies, may represent a promising treatment for patients with KRAS G12C mutations.

BBP-398 is a potential best-in-class SHP2 inhibitor. Earlier this year, BridgeBio entered into a non-exclusive, co-funded clinical collaboration with Bristol-Myers Squibb to evaluate the combination of BBP-398 and the anti-PD-1 therapy Opdivo (nivolumab) for the treatment of patients with advanced solid tumors harboring KRAS mutations.

In August 2020, BridgeBio also entered into a strategic collaboration with LianBio to jointly conduct clinical development and commercialization of BBP-398 in combination with various drugs in mainland China and other major Asian markets, for the treatment of solid tumors such as non-small cell lung cancer, colorectal cancer, and pancreatic cancer.

Currently, BridgeBio is also advancing a Phase 1 clinical trial of the SHP2 inhibitor BBP-398 for the treatment of patients with solid tumors caused by mutations in the MAPK signaling pathway (including RAS and receptor tyrosine kinase genes).

Reference Source: BridgeBio Announces Clinical Collaboration with Amgen to Study BBP-398, a Potentially Best-in-class SHP2 Inhibitor, in Combination with LUMAKRAS® (sotorasib) in Advanced Solid Tumors with the KRAS G12C Mutation