BridgeBio Oncology Therapeutics reported data from its phase 1 Onkoras-101 trial suggesting its KRAS G12C inhibitor BBO-8520 may be more effective than existing drugs in the class.
The company said BBO-8520 achieved a 65% overall response rate (ORR) in second-line KRAS G12C-mutant non-small cell lung cancer (NSCLC) among 17 patients; that figure includes one unconfirmed response. Excluding the unconfirmed response yields a confirmed ORR of 58%. By comparison, Amgen’s Lumakras produced a 36% ORR and Bristol Myers Squibb’s Krazati a 43% ORR in trials supporting accelerated approval. Revolution Medicines’ elironrasib, which also targets the on state of KRAS G12C, has reported a 56% ORR in a similar setting.
BBO-8520 targets both the “on” and “off” states of KRAS G12C, while approved drugs only target the off state. BridgeBio says this dual-state activity could increase potency and lower the drug levels needed for efficacy.
BridgeBio also presented early combination data for BBO-8520 plus the PD-1 inhibitor pembrolizumab (Keytruda). Among eight patients — both treatment-naive and previously treated — five had partial responses: three of three in the treatment-naive cohort and two of five in the treatment-experienced cohort (all of whom had prior KRAS G12C inhibitor therapy). Responses were observed across PD-L1 expression levels, including two in patients with 1–2% expression.
Combining KRAS G12C inhibitors with checkpoint inhibitors has been challenging previously, with liver enzyme elevations derailing some efforts. BridgeBio reported one case of grade 3 liver enzyme elevation in the BBO-8520/Keytruda cohort, which the company attributed to concomitant medications; the event resolved and the patient remained on therapy.
Investors reacted positively to the update, sending BridgeBio Oncology Therapeutics’ stock up about 4% on Wednesday. BridgeBio expects another BBO-8520 update in the second half of 2026 and plans a combination program pairing the agent with its PI3Kα:RAS breaker BBO-10203.
Leave a Reply