BBO-8520 Receives FDA Fast Track Designation in KRAS G12C–Mutated Metastatic NSCLC

The FDA has granted fast track designation to the investigational oral agent BBO-8520 for the treatment of adult patients with previously treated KRAS G12C–mutated metastatic non–small cell lung cancer (NSCLC).1

BBO-8520 is being evaluated in a phase 1 study (NCT06343402) of adult patients with pretreated KRAS G12C–mutated NSCLC and colorectal cancer (CRC). In June 2024, BridgeBio Oncology Therapeutics announced that the first patient was dosed in the phase 1 study of BBO-8520.2 BBO-8520 is designed to provide optimal target coverage and to address KRAS G12C amplification and receptor tyrosine kinase activation by inhibiting the on and off state.1

“Receiving fast track designation for BBO-8520 is a significant milestone in our efforts to overcome the limitations of existing therapies for KRAS G12C–mutant cancers,” Yong Ben, MD, MBA, chief medical and development officer of BridgeBio Oncology Therapeutics, stated in a news release. “BBO-8520 represents a first-in-class approach with potential to address high unmet medical needs and shift the paradigm for cancer treatment. We will continue to work closely with the FDA to expedite the development of BBO-8520, which is currently being evaluated in a phase 1 study of [patients with] KRAS G12C[–mutant] NSCLC pretreated with first-generation KRAS G12C ‘OFF’ inhibitors or with no prior KRAS G12C–targeted therapy experience.”

The open-label, multicenter phase 1 trial is the first-in-human study to examine the safety, tolerability, and pharmacokinetics of BBO-8520.3 The study is enrolling patients with locally advanced or metastatic KRAS G12C–mutated NSCLC or CRC who have measurable disease by RECIST 1.1 criteria and an ECOG performance status of 0 or 1.

Patients with a malignancy within the past 2 years, untreated brain metastases, and known hypersensitivity to BBO-8520 or its excipients will be excluded. In cohorts 2a and 2b, those with known hypersensitivity to pembrolizumab (Keytruda) or its excipients, active autoimmune disease or a history of autoimmune disease that might recur, and a history of interstitial lung disease/pneumonitis that necessitated steroid use or current interstitial lung disease/pneumonitis are not eligible for the trial.

In the dose escalation phase, patients will receive oral daily BBO-8520 at various dose levels as monotherapy in cohort 1a and in combination with intravenous pembrolizumab in cohort 1b. In the dose expansion phase, patients will receive the assigned dose of BBO-8520 either as monotherapy (cohort 2a) and in combination with pembrolizumab (cohort 2b).

The coprimary end points are adverse effects and dose-limiting toxicities. Secondary end points include progression free-survival and duration of response per RECIST 1.1 criteria, overall survival, and the pharmacokinetic characteristics of BBO-8520, including area under the curve, peak plasma drug concentration (Cmax), time to Cmax, and half-life.

The study is enrolling patients at 15 sites in the US and Australia. The estimated primary completion date is August 2027.

References

1. BridgeBio Oncology Therapeutics (BBOT) granted U.S. FDA fast track designation for BBO-8520 for KRASG12C-mutated metastatic non-small cell lung cancer. News release. BridgeBio Oncology Therapeutics. January 9, 2025. Accessed January 9, 2025. https://www.businesswire.com/news/home/20250109170439/en/BridgeBio-Oncology-Therapeutics-BBOT-Granted-U.S.-FDA-Fast-Track-Designation-for-BBO-8520-for-KRASG12C-Mutated-Metastatic-Non-Small-Cell-Lung-Cancer
2. BridgeBio Oncology Therapeutics announces first patient dosed with BBO-8520 in the ph. 1 ONKORAS-101 trial for KRASG12C NSCLC. BridgeBio Oncology Therapeutics. June 6, 2024. Accessed January 9, 2025. https://www.businesswire.com/news/home/20240606977682/en/BridgeBio-Oncology-Therapeutics-announces-first-patient-dosed-with-BBO-8520-in-the-Ph.-1-ONKORAS-101-trial-for-KRASG12C-NSCLC
3. Study of BBO-8520 in adult subjects with KRASG12C non-small cell lung and colorectal cancer. ClinicalTrials.gov. Updated October 30, 2024. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT06343402