Trial-by-gene · KRAS G12C

Active clinical trials enrolling KRAS G12C NSCLC

Decision-support aid only — eligibility decisions must be confirmed against the actual trial protocol and the patient's medical record. Trial counts and statuses change daily; this page is for orientation, not adjudication.

KRAS G12C NSCLC trials concentrate on three frontiers: (1) combination strategies to extend sotorasib or adagrasib durability (ICI combos, SHP2 inhibitor combos, MEK/ERK combos), (2) post-G12Ci resistance trials targeting bypass-track activation, and (3) next-generation KRAS inhibitors with better CNS penetration and broader KRAS-mutant coverage.

See the KRAS G12C cheat sheet for the underlying biology and STK11/KEAP1 co-mutation modifiers.

Browse the live listing

Search ClinicalTrials.gov for actively recruiting NSCLC trials with KRAS G12C-directed interventions.

Open ClinicalTrials.gov listing

Source: ClinicalTrials.gov, US National Library of Medicine. Trial-listing data is in the public domain. Use of ClinicalTrials.gov data must comply with the NLM terms of use.

Representative trial phases and designs

Phase III, post-platinum monotherapy

Sotorasib vs docetaxel for KRAS G12C NSCLC after platinum chemotherapy (CodeBreaK 200).

Example: NCT04303780

Phase II, sotorasib + ICI combinations

Sotorasib + pembrolizumab or atezolizumab combinations, navigating overlapping hepatotoxicity AE.

Phase I, next-generation KRAS G12C inhibitors

Divarasib, glecirasib, and other next-gen G12Ci with improved durability or CNS coverage.

Phase I/II, KRAS G12D + pan-KRAS inhibitors

Tumor-agnostic pan-KRAS-mutant trials (RMC-6236) increasingly enrolling KRAS G12C patients post-G12Ci.

Frequently asked questions

Which trials are most relevant for sotorasib- or adagrasib-naive patients?
CodeBreaK and KRYSTAL trials in their first-line settings, plus combination trials testing G12Ci + ICI or G12Ci + chemotherapy upfront. Sequencing decisions depend on STK11/KEAP1 co-mutation status.
What about post-resistance trials?
Post-G12Ci resistance is heterogeneous (secondary KRAS mutations, MET/RAS amplification, MAPK pathway reactivation). Bypass-track-specific trials and SHP2/SOS1 combination trials are the most active resistance-targeting frontiers.

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