BridgeBio Oncology Therapeutics' BBO-8520, an investigational oral therapy, has received Fast Track designation from the FDA for the treatment of adult patients with previously treated KRASG12C-mutated metastatic non-small cell lung cancer (NSCLC). This designation is intended to accelerate the development and review process for drugs addressing unmet medical needs in serious conditions.
BBO-8520 is designed to inhibit both the active ("ON") and inactive ("OFF") states of the KRASG12C protein, a mechanism intended to overcome resistance to existing therapies. Preclinical models have demonstrated that BBO-8520 effectively inhibits tumor growth, even in cases where resistance to sotorasib (Lumakras) has developed.
ONKORAS-101 Phase 1 Trial
Currently, BBO-8520 is being evaluated in the Phase 1 ONKORAS-101 trial (NCT06343402), a first-in-human, open-label, multicenter study. This trial aims to assess the safety, tolerability, and pharmacokinetics of BBO-8520 as a single agent and in combination with pembrolizumab (Keytruda) in patients with KRASG12C-mutated NSCLC and colorectal cancer. The trial includes a dose escalation phase (cohorts 1a and 1b) and a dose expansion phase (cohorts 2a and 2b).
Patients enrolled in the trial have histologically documented locally advanced or metastatic KRASG12C-mutated NSCLC, measurable disease by RECIST v1.1, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Exclusion criteria include malignancy within the last 2 years, untreated brain metastases, and known hypersensitivity to BBO-8520 or its excipients. For cohorts 2a and 2b, additional exclusion criteria include known hypersensitivity to pembrolizumab, active autoimmune disease, or a history of interstitial lung disease or pneumonitis.
The primary endpoints of the study are the incidence and severity of treatment-emergent adverse events (AEs) and serious AEs, as well as dose-limiting toxicities. Secondary endpoints include progression-free survival, duration of response, overall survival, and pharmacokinetics of BBO-8520, including Cmax, time to Cmax, and half-life.
Industry Perspective
"Receiving fast track designation for BBO-8520 is a significant milestone in our efforts to overcome the limitations of existing therapies for KRASG12C-mutant cancers," said Yong Ben, MD, chief medical and development officer of BridgeBio Oncology Therapeutics. "BBO-8520 represents a first-in-class approach with potential to address high unmet medical needs and shift the paradigm for cancer treatment."
The first patients were dosed with BBO-8520 in June 2024, and the estimated primary completion date for the study is August 2027.
