BridgeBio Oncology Therapeutics (BBOT) reported phase 1 data suggesting its KRAS G12C inhibitor BBO-8520 may outperform existing agents in second-line non–small cell lung cancer (NSCLC). In the Onkoras-101 trial the company reported a 65% overall response rate (ORR) among 17 patients; excluding one unconfirmed response the confirmed ORR was 58%.
BBO-8520 targets both the active (“on”) and inactive (“off”) states of KRAS G12C, whereas approved drugs such as Amgen’s Lumakras and Bristol Myers Squibb’s Krazati target only the off state. In trials supporting accelerated approval in second-line NSCLC, Lumakras produced a 36% ORR and Krazati 43%. Revolution Medicines’ elironrasib, which also targets the on state, has reported a 56% ORR in a similar setting and is further advanced clinically.
BridgeBio also presented early results for BBO-8520 combined with Keytruda. Among eight patients (treatment‑naive and treatment‑experienced), five achieved partial responses: 3 of 3 in the treatment‑naive cohort and 2 of 5 in the treatment‑experienced cohort, the latter of whom had prior KRAS G12C inhibitor therapy. Responses were seen across PD‑L1 expression levels, including two responses in patients with 1–2% PD‑L1. There was one grade 3 elevation in liver enzymes; the company attributed this to co‑medications, reported the event resolved, and said the patient remained on therapy.
Combining KRAS G12C inhibitors with checkpoint inhibitors has previously been challenging because of liver toxicity, notably disrupting plans for a Lumakras/checkpoint inhibitor regimen. BridgeBio said BBO-8520’s therapeutic index could alleviate this issue, but cautioned that the current combination data are very preliminary.
Investors reacted positively to the update, pushing BBOT shares up about 4% on Wednesday. BridgeBio plans another BBO-8520 update in the second half of 2026 and intends to test the compound in combination with its PI3Kα:RAS breaker BBO-10203. All findings remain preliminary and will need confirmation in larger trials.
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