FDA Grants BBO-8520 Fast Track Designation for KRASG12C-Mutant mNSCLC

The decision was supported by efficacy findings from the phase 1 ONKORAS-101 trial, which evaluated the therapy in KRASG12C non–small cell lung cancer.

The FDA has granted BBO-8520 fast track designation as an oral therapy for the treatment of adult patients with previously treated KRAS^G12C-mutatated metastatic non–small cell lung cancer (NSCLC), according to a news release from the drug’s developer, BridgeBio Oncology Therapeutics.¹

The FDA decision was supported by efficacy findings from the ongoing phase 1 ONKORAS-101 trial (NCT06343402), which is currently assessing the safety, tolerability, preliminary antitumor activity, and pharmacokinetics of the oral therapy in KRAS^G12C metastatic NSCLC. BBO-8520, which is designed as an inhibitor to provide optimal target coverage and to address KRAS^G12C amplification and tyrosine kinase receptor activation, drove substantial tumor growth inhibition in multiple preclinical models, even after displaying sotorasib (Lumakras) resistance.

“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, chief medical and development officer of BBOT, said in the news release.¹ “BBO-8520 represents a first-in-class approach with the 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 NSCLC pre-treated with first generation KRAS^G12C “OFF” inhibitors or with no prior KRAS^G12C targeted therapy experience.”

The phase 1a/1b open-label trial enrolled 229 adult patients with advanced KRAS^G12C-mutant NSCLC and colorectal cancers to receive either BBO-8520 monotherapy or BBO-8520 in combination with pembrolizumab (Keytruda).² Patients in this study were assigned to 1 of 4 cohorts: cohorts 1a and 1b were dose escalation cohorts evaluating BBO-8520 monotherapy and in combination with pembrolizumab, respectively, and cohorts 2a and 2b were dose expansion cohorts assessing the matching interventions.

Patients enrolled in the 1a cohort received BBO-8520 at different dose levels once daily as a monotherapy. In the 1b cohort, BBO-8520 was given at different dose levels once daily in combination with pembrolizumab. Patients in cohorts 2a and 2b received matching regimens once daily at the maximum tolerated dose level found during the dose escalation phase.

The coprimary end points of the study are incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), and dose-limiting toxicities. Secondary end points include progression-free survival, duration of response, overall survival, and pharmacokinetics.

Eligibility criteria for the trial include histologically confirmed locally advanced or metastatic KRAS^G12C-mutated NSCLC or colorectal cancer, measurable disease by RECIST v1.1, and an ECOG performance status of 0 or 1.

Patients were excluded if they had a protocol-specified malignancy within the last 2 years, those with untreated brain metastases, and those with a known hypersensitivity to BBO-8520 or its excipients. For cohorts 2a and 2b, patients with a known hypersensitivity to pembrolizumab, those with an active autoimmune disease or history of an autoimmune disease that might recur, and patients with a history of interstitial lung disease (ILD) or pneumonitis that required steroids, as well as current ILD or pneumonitis, were excluded.

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://tinyurl.com/y8mk9dr3
2. Study of BBO-8520 in adult subjects with KRASG12C non-small cell lung and colorectal cancer. ClinicalTrials.gov. Updated October 30, 2024. Accessed January 8, 2025. https://tinyurl.com/4c9zztfe