Shanghai-based biotech D3 Bio reported response rates above 78% for elisrasib (D3S-001) in previously untreated KRAS G12C–mutant non-small cell lung cancer at ASCO 2026. The result, if it holds in larger studies, would mark the first time a KRAS-targeted agent has demonstrated competitive efficacy in the first-line setting.
The data come from an ongoing Phase I/II study enrolling patients with KRAS G12C–mutant solid tumors. In the first-line monotherapy cohort, 43 patients received elisrasib 600 mg once daily in 21-day cycles; 41 were efficacy-evaluable at a median follow-up of 8.5 months. The overall response rate was 78.0% across all PD-L1 expression levels, including a 76.2% ORR in patients with PD-L1 tumor proportion score below 1% — a subgroup that typically responds poorly to checkpoint inhibition alone. Median progression-free survival reached 12.4 months. The safety profile was notably clean: Grade 3 or higher treatment-related adverse events occurred in just 7% of patients, with no discontinuations and no dose reductions required.
In the combination cohort, 52 patients received elisrasib at the same 600 mg daily dose alongside Merck's Keytruda (pembrolizumab) 200 mg every three weeks; 48 were efficacy-evaluable at a median follow-up of 5.7 months. The ORR was 81.3%, with a 12-month PFS rate of 53.7%. Grade 3 or higher TRAEs rose to 32.7%, with most severe events attributed to pembrolizumab rather than elisrasib, and no new safety signals emerged for the KRAS inhibitor.
Competitive context
Elisrasib is a covalent inhibitor that targets the GDP-bound, inactive form of KRAS G12C, designed for what D3 Bio describes as complete target coverage at its recommended Phase II dose. The first-generation agents in this class — Amgen's Lumakras (sotorasib) and Mirati's Krazati (adagrasib) — are approved only in patients who have received at least one prior systemic therapy, leaving the first-line setting entirely occupied by IV immunotherapy regimens, with or without chemotherapy. Despite validating KRAS G12C as a druggable target, first-generation inhibitors have generally produced shorter progression-free survival than established immunotherapy regimens in untreated NSCLC, raising questions about whether KRAS-targeted therapy alone can compete in the frontline setting. Cross-trial comparisons are limited by differences in patient selection, follow-up duration, and study design, but the 78% monotherapy ORR and 12.4-month median PFS reported here for elisrasib exceed the historical benchmarks associated with pembrolizumab monotherapy in biomarker-unselected first-line NSCLC populations.
Multiple next-generation KRAS G12C inhibitors are attempting to move beyond the limitations of first-generation agents, which demonstrated clinical activity in previously treated patients but have struggled to establish a role in the frontline setting. Companies including D3 Bio, Revolution Medicines, Verastem, and others are pursuing combinations and next-generation molecules designed to deliver deeper and more durable pathway suppression. D3 Bio said its latest data support advancing elisrasib into Phase III randomized studies, though no timeline or trial design has been disclosed.
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