On March 23, 2023 BridgeBio Pharma, Inc., (Nasdaq: BBIO) (BridgeBio), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported that the first patient with non-small cell lung cancer (NSCLC) has been dosed in its Phase 1/2 clinical trial of BBP-398, an investigational SHP2 inhibitor, with Bristol Myers Squibb’s OPDIVO (nivolumab) in advanced solid tumors with KRAS mutations (NCT05375084) (Press release, BridgeBio, MAR 23, 2023, View Source [SID1234629237]).

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KRAS mutations occur in approximately 27% of NSCLC cases and approximately 17% of malignant solid tumors. By combining SHP2 inhibition with KRAS inhibition in patients, there is potential to prevent oncogenesis and overactive cellular proliferation.

"SHP2 has been shown to be a key regulator of both tumor and immune cell signaling. 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," said Eli Wallace, Ph.D., chief scientific officer of oncology at BridgeBio. "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."

The Phase 1 study will include a dose escalation period followed by dose expansion, and is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of BBP-398 in combination with OPDIVO. Both the dose escalation and expansion periods will enroll patients who were unresponsive to standard of care with advanced NSCLC with a KRAS mutation. The dose expansion period will evaluate the antitumor activity of BBP-398 in combination with OPDIVO.

In May 2022, BridgeBio entered into an exclusive license agreement with Bristol Myers Squibb to develop and commercialize BBP-398 in oncology worldwide, except for in mainland China and other Asian markets. These territories are part of BridgeBio’s separate strategic collaboration with LianBio announced in 2020. The 2022 agreement with Bristol Myers Squibb expands upon the earlier agreement between the companies signed in 2021 to investigate the combination of BBP-398 with OPDIVO (nivolumab) in patients with advanced solid tumors with KRAS mutations.

Additionally, BridgeBio has a non-exclusive clinical collaboration with Amgen to evaluate the combination of BBP-398 with LUMAKRAS in patients with advanced solid tumors with the KRASG12C mutation.

BBP-398, as a monotherapy or in combination with other targeted therapies, could potentially be a promising therapy for patients with KRAS mutations. Initial Phase 1 data from the ongoing BBP-398 trial is expected in 2023.

OPDIVO (nivolumab) is a trademark of Bristol-Myers Squibb Company.

About BBP-398
BBP-398 is a SHP2 inhibitor that is being developed for difficult-to-treat cancers and was founded through a collaboration with The University of Texas MD Anderson Cancer Center’s Therapeutics Discovery division. 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. In May 2022, BridgeBio entered an exclusive license with Bristol Myers Squibb to develop and commercialize BBP-398, a potentially best-in-class SHP2 inhibitor. Additionally, BridgeBio has a strategic collaboration with LianBio for clinical development and commercialization of BBP-398 in combination with various agents in solid tumors such as non-small cell lung cancer, colorectal and pancreatic cancer, in mainland China and other Asian markets and clinical collaborations; with Bristol Myers Squibb for combination with OPDIVO (nivolumab) in patients with advanced solid tumors with KRAS mutations; and with Amgen for combination with LUMAKRAS (sotorasib), Amgen’s KRASG12C inhibitor, in patients with advanced solid tumors with KRASG12C mutations.