FDA Grants Fast Track Designation to BBP-398 Plus Sotorasib for Advanced KRAS G12C–Mutant NSCLC

BBP-398 in combination with sotorasib (Lumakras) was granted fast track designation by the FDA for patients with KRAS G12C–mutated locally advanced NSCLC, according to a press release from BridgeBio Pharma.

The first patient was recently dosed as part of a phase 1/2 Argonaut trial (NCT05480865) assessing the combination in patients with advanced KRAS G12C–mutant solid tumors. This study will include a dose escalation and expansion portion to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the treatment combination. In the dose expansion portion of the trial, patients with NSCLC who have a KRAS G12C mutation but have not previously been exposed to KRAS G12C inhibitors will receive treatment. Data is expected by the end of 2024.

BBO-398 is a SHP2 inhibitor that has been developed for difficult-to-treat cancers. The protein SHP2 helps to link growth factors with cytokine and integrin signaling with downstream RAS/ERK MAPK pathway to regulate cellular proliferation and survival. When combining SHP2 inhibition with KRAS G12C inhibition in patients with KRAS G12C mutations, oncogenesis may be prevented with overactive cellular proliferation.

“The survival rate following a diagnosis of NSCLC with a KRAS mutation is extremely poor. We are hopeful that by launching this clinical trial with Amgen, we may be able to fill the current gap in unmet medical need for these cancer patients,” Frank McCormick, PhD, chairman of oncology at BridgeBio, said in the press release. “We are grateful the FDA has granted our program fast track designation and are hopeful it will allow us to address the needs of these patients more quickly following diagnosis.”

BBP-398 is also being used in combination with nivolumab (Opdivo) in patients in China and other Asian countries for patients with NSCLC and pancreatic cancer. In patients with advanced solid tumors with KRAS mutations, nivolumab can also be used in combination with BBP-398.

“To date, preclinical data for SHP2 inhibition has shown promise in unlocking possible combination strategies to treat patients [diagnosed with] a range of cancers, including NSCLC. By combining SHP2 inhibition with KRAS G12C inhibition, there is potential for this therapeutic arsenal to be impactful for patients since it could prevent overactive cellular proliferation and oncogenesis,” Benjamin G. Neel, MD, PhD, Co-founder of Navire Pharma Inc. (Navire), a BridgeBio company, and director of the L/I Perlmutter Cancer Center at NYU Langone and professor of medicine at NYU Grossman SoM.1, concluded.

Reference

BridgeBio Pharma announces first lung cancer patient dosed in phase 1/2 trial and US FDA fast track designation for SHP2 inhibitor BBP-398 in combination with Amgen’s LUMAKRAS® (sotorasib). News Release. BridgeBio Pharma. October 11, 2022. Accessed October 13, 2022. https://bit.ly/3g0seLM