FDA Fast Tracks BBP-398 and Sotorasib Combination for Adults With Advanced KRAS G12C+ NSCLC


Considering the potential to fill a treatment gap in the KRAS G12C-mutant non–small cell lung cancer population, the FDA has granted a fast track designation to the combination of BBP-398 and sotorasib.

The FDA has granted fast track designation (FTD) to BBP-398 in combination with sotorasib (Lumakras) for the treatment of adult patients with previously-treated, KRAS G12C-mutated, metastatic non–small cell lung cancer (NSCLC).1

The FTD was announced in a press release by BridgeBio Pharma, Inc. It was granted based on the combinations ability to serve an unmet medical need for patients with KRAS G12C-mutated NSCLC.

“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,” said Frank McCormick, PhD, chairman of oncology at BridgeBio, 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 a SHP2 inhibitor, which is known to regulate cellular proliferation and survival by connecting growth factor, cytokine, and integrin signaling with the downstream RAS/ERK MAPK pathway. preclinical research suggests that the SHP2 inhibitor may have synergy with sotorasib. An evaluation of the safety/tolerability, andante-tumor activity of BBP-398 and sotorasib is ongoing in the phase 1 Argonaut clinical trial (NCT05480865).2

About the Phase 1 Argonaut Trial

Trial Name: A Phase 1 Study of the SHP2 Inhibitor BBP-398 (Formerly Known as IACS-15509) in Combination With the KRAS-G12C Inhibitor Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation

ClinicalTrials.gov Identifier: NCT05480865

Sponsor: Navire Pharma Inc., a BridgeBio company

Recruitment Contact: Danielle.Mcmullin@bridgebio.com 415-676-8911

Completion Date: June 2025

"To date, preclinical data for SHP2 inhibition has shown promise in unlocking possible combination strategies to treat patients suffering from 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. I am extremely pleased to see that work from our group and others has now reached the clinic, where we will be able to study the benefit it could have for cancer patients with KRAS G12C mutations," said Benjamin G. Neel, MD, PhD, co-founder of Navire Pharma Inc., a BridgeBio company, and director of the L/I Perlmutter Cancer Center at NYU Langone and Professor of Medicine at NYU Grossman SoM,” in the press release.1

The first patient with KRAS G12C-mutated NSCLC has been dosed with the investigational combination in the Argonaut trial, according to the announcement by BridgeBio Pharma, Inc.

The study will be conducted in 2 parts. Phase 1a is the dose escalation portion of the study. The goal in the phase 1a stage is to evaluate safety/tolerability and determining the recommended dose to administer in the phase 1b stage. In phase 1b, the primary goals are to evaluate safety/tolerability, as well as antitumor activity, which will be defined by the primary end point overall response rate, and the secondary end points of duration or response, progression-free survival, and overall survival.2

The study will enroll up to 85 patients with advanced solid tumors that harbor KRAS G12C mutations. The prospective completion date for the study is June 2025.


1. 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). https://bit.ly/3COxkUe

2. SHP2 Inhibitor BBP-398 in combination with sotorasib in patients with advanced solid tumors and a KRAS-G12C mutation (Argonaut). Clinicaltrials.gov. Updated August 17, 2022. Accessed October 12, 2022. https://clinicaltrials.gov/ct2/show/NCT05480865?term=BBP-398&draw=2&rank=3

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