NEW YORK – BridgeBio Pharma on Thursday said the first KRAS-mutant advanced non-small cell lung cancer patient has received its SHP2 inhibitor, BBP-398, and Bristol Myers Squibb's checkpoint inhibitor Opdivo (nivolumab) in a Phase I/II trial.
In the Phase I portion, BridgeBio will enroll up to 45 participants with KRAS-mutant advanced NSCLC who have failed standard treatment in the trial. Researchers will evaluate the safety, tolerability, and preliminary efficacy of the BBP-398-Opdivo combination. The company is expecting an initial data readout from the Phase I dose-expansion and -escalation portion of the trial this year.
The overall aim of the Phase I/II trial is to explore the activity of the SHP2-checkpoint inhibitor combo in KRAS-mutated advanced solid tumors, not just NSCLC. Approximately 27 percent of NSCLC patients harbor KRAS mutations in their tumors, and these aberrations occur in around 17 percent of solid tumors.
"In KRAS-mutant tumors, SHP2 promotes survival, proliferation, and decreased immunogenicity by driving the active form of KRAS, while in immune cells, it associates with PD-1, which leads to immunosuppression in the tumor microenvironment," Eli Wallace, BridgeBio's CSO of oncology, said in a statement. "By partnering with Bristol Myers Squibb on this trial, we hope to show that targeting PD-1 with a two-prong approach can unlock the potent benefits of immunotherapy against this cancer and provide new treatment options for patients who need them."
Last year, BMS licensed BBP-398 from BridgeBio to develop and commercialize the drug worldwide, except for in mainland China and other Asian markets, in a deal worth more than $905 million. Under that agreement, BridgeBio is overseeing ongoing Phase I studies of BBP-398, and BMS will take over all future clinical trials.
Palo Alto, California-based BridgeBio is also studying BBP-398 in combination with Amgen's Lumakras (sotorasib) in patients with advanced solid tumors driven by the KRAS G12C mutation. The firm is exploring the drug as a monotherapy in solid tumors harboring MAPK signaling pathway genetic mutations.