BridgeBio Pharma has entered a clinical collaboration to assess BBP-398 in combination with Bristol Myers Squibb (BMS)’s Opdivo (nivolumab) to treat advanced solid tumours with KRAS mutations.
With the collaboration, BridgeBio aims to offer a new treatment that is effective against difficult-to-treat cancers.
Developed in alliance with the Therapeutics Discovery unit of the University of Texas MD Anderson Cancer Center, BBP-398 inhibits src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2).
SHP2 connects growth factor, cytokine and integrin signalling with the downstream RAS/ERK MAPK pathway to modulate cellular proliferation and survival.
The SHP2 pathway’s overactivity is frequently driven by different genetic mutations. This overactivity is associated with various cancers and resistance to multiple targeted treatments.
BridgeBio Pharma oncology chairman Frank McCormick said: “Cancers that are driven by hyperactive MAPK signalling, including certain RAS mutations such as KRASG12C, may be sensitive to SHP2 inhibition.
“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.”
The non-exclusive, co-funded partnership will involve a Phase I/II clinical trial of BBP-398 plus Opdivo as doublet treatment, and BBP-398 plus Opdivo along with a KRASG12C inhibitor as triplet treatment.
During the trial, the combinations will be analysed for their safety and preliminary efficacy as first- and second-line therapies in non-small cell lung cancer (NSCLC) patients with KRAS mutations.
As per the deal, BridgeBio will fund the trial while BMS will supply nivolumab. The partners will split the clinical development expenses related to the study.
BridgeBio is presently conducting a Phase I trial for solid tumours with the MAPK signalling pathway mutations such as RAS and receptor tyrosine kinase genes.
Earlier this month, BMS reported that Opdivo plus Yervoy failed to meet the primary goals of Phase III CheckMate -651 trial in platinum-eligible recurrent or metastatic squamous cell carcinoma of the head and neck patients.
