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Last updated: October 29, 2026 (pan-KRAS G12R coverage note added)
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Find matching trials →KRAS (Kirsten rat sarcoma viral oncogene homolog) is a small GTPase that cycles between an inactive GDP-bound 'OFF' state and an active GTP-bound 'ON' state. In the ON state, KRAS activates downstream MAPK and PI3K pathways driving cell proliferation. Activating KRAS mutations (most commonly at codon 12, 13, or 61) lock the protein in the ON state, driving constitutive growth signaling. KRAS is the most frequently mutated oncogene in human cancer:
KRAS was considered undruggable for decades because the smooth GTP-binding surface lacks pockets for small-molecule binding. The 2013 discovery of an allosteric pocket adjacent to the mutant G12C cysteine made covalent KRAS G12C inhibitors possible — sotorasib and adagrasib lock the cysteine sulfur of mutant KRAS G12C in the OFF state, preventing ON-state signaling.
Three target mechanisms now span the KRAS-inhibitor class: KRAS G12C 'OFF' inhibitors (sotorasib, adagrasib, divarasib, olomorasib, garsorasib, glecirasib, calderasib — bind GDP-bound OFF state of G12C specifically); KRAS G12D inhibitors (MRTX1133, HRS-4642, VS-7375, INCB161734 — covalent binders targeting the G12D aspartic acid); KRAS G12D degraders (setidegrasib ASP3082 — PROTAC-like degraders of mutant KRAS protein); and pan-RAS RAS(ON) inhibitors (daraxonrasib RMC-6236, zoldonrasib RMC-9805, RMC-6291 — bind the GTP-bound ON state and cover multiple KRAS isoforms simultaneously).
| Drug | Sponsor | Target / Class | Regulatory Status | Lead Indications |
|---|---|---|---|---|
| Sotorasib (Lumakras, AMG510) | Amgen | KRAS G12C covalent 'OFF' | FDA May 2021: KRAS G12C NSCLC (post-platinum). CodeBreaK pivotal trials. | NSCLC (Ph3 + chemo NCT05920356; CRC + panitumumab + FOLFIRI NCT06252649) |
| Adagrasib (Krazati, MRTX849) | Mirati / Bristol Myers Squibb | KRAS G12C covalent 'OFF' | FDA Dec 2022: NSCLC (accelerated approval). FDA Jun 2024: KRAS G12C CRC + cetuximab (accelerated approval) — withdrawn Sep 1, 2026 (KRYSTAL-10 missed PFS/OS). | NSCLC (Ph3 + pembrolizumab + chemo NCT06875310), CRC (KRYSTAL-1 + cetuximab) |
| Divarasib (GDC-6036) | Genentech / Roche | KRAS G12C | Investigational. Ph3 NCT07541170 (divarasib vs IC chemo) + Ph3 NCT06793215 (divarasib + pembrolizumab). | NSCLC (Ph3) |
| Daraxonrasib (RMC-6236) | Revolution Medicines | Pan-RAS 'ON' (KRAS + NRAS + HRAS, all isoforms) | FDA-approved August 26, 2026 (RASONQUE) for metastatic pancreatic adenocarcinoma after ≥1 prior systemic therapy (RASolute 302: OS 13.2 vs 6.7 months, HR 0.40); EU CHMP positive opinion October 15, 2026. Still investigational in other settings — Phase 3 trials NCT06881784 (RASolve 1L NSCLC), NCT07491445 (1L pancreatic + GnP), NCT07252232 (resected pancreatic adjuvant). Drug page: /drugs/daraxonrasib. | Pancreatic (approved 2L+; Ph3 1L + adjuvant), NSCLC (Ph3 RASolve) |
| Olomorasib (LY3537982) | Eli Lilly | KRAS G12C | Investigational. Ph3 NCT06119581 (1L olomorasib + pembrolizumab ± chemo) + Ph3 NCT06890598 (+ SoC). | NSCLC (Ph3 1L) |
| Garsorasib (D-1553) | InventisBio | KRAS G12C | NMPA-approved (China, Nov 2024) for previously treated KRAS G12C NSCLC; not FDA-approved. Ph3 NCT06300177 (D-1553 vs docetaxel in NSCLC) + Ph3 NCT07174908 (+ IN10018). | NSCLC (Ph3) |
| Glecirasib (JAB-21822) | Jacobio Pharma | KRAS G12C | NMPA conditional approval (China, May 2025) for previously treated KRAS G12C NSCLC; not FDA-approved. Ph3 NCT06416410 (glecirasib + JAB-3312 SHP2 inhibitor combo). | NSCLC (Ph3 1L SHP2 combo) |
| Calderasib (MK-1084) | Merck | KRAS G12C | Investigational. Ph3 NCT06345729 (calderasib + pembrolizumab) + Ph3 NCT07431827 (adjuvant resected stage IIA-IIIB NSCLC). | NSCLC (Ph3 + pembro + adjuvant) |
| Zoldonrasib (RMC-9805) | Revolution Medicines | KRAS G12D RAS(ON) | Investigational. Ph3 NCT07621718 (zoldonrasib + chemo vs placebo + chemo). | KRAS G12D pan-tumor (Ph3 chemo combo) |
| RMC-6291 | Revolution Medicines | KRAS G12C RAS(ON) | Investigational. Early-phase combination with daraxonrasib. | NSCLC + pan-tumor |
| MRTX1133 | Mirati / Bristol Myers Squibb | KRAS G12D covalent | Investigational. Ph1/2. | Pancreatic + CRC + NSCLC G12D |
| Setidegrasib (ASP3082) | Astellas | KRAS G12D PROTAC-like degrader | Investigational. Ph3 NCT07566052 (setidegrasib vs docetaxel in NSCLC) + Ph3 NCT07409272 (+ chemo). | NSCLC + pan-tumor (Ph3) |
| HRS-4642 | Hengrui Pharma | KRAS G12D | Investigational. 11 corpus trials — largest Chinese KRAS G12D program. | Pancreatic + CRC + NSCLC G12D |
| VS-7375 | Verastem | KRAS G12D | Investigational. Featured in Task 332 Egyptian pancreatic patient's results (rank #8). | Pancreatic + solid tumors G12D |
| JAB-23E73 | Jacobio Pharma | KRAS-related | Investigational. Featured in Task 332 Egyptian pancreatic patient's results (rank #9). | Solid tumors |
| INCB161734 | Incyte | KRAS G12D | Investigational. Ph3 NCT07522073 (chemo ± INCB161734). | Solid tumors G12D (Ph3 chemo combo) |
| KRAS G12V TCR cell therapy (NCT04146298) — related class | NCI / academic | KRAS G12V × TCR T-cell therapy (HLA-A*11:01-restricted) | Investigational. Phase 1/2 in HLA-A*11:01+ KRAS G12V+ solid tumors. The trial the Egyptian pancreatic patient examined 3 times. | Pancreatic + CRC + solid tumors G12V (HLA-A*11:01+ only) |
The first FDA-approved KRAS-targeted oral small molecule (May 2021). Sotorasib was approved for adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy, based on the CodeBreaK 100 pivotal trial. The CodeBreaK 200 Phase 3 confirmatory trial demonstrated PFS benefit vs docetaxel in 2L NSCLC. Current Phase 3 program: NCT05920356 (sotorasib + platinum doublet vs pembrolizumab-containing comparator in 1L NSCLC), NCT06252649 (sotorasib + panitumumab + FOLFIRI vs FOLFIRI in KRAS G12C CRC — the metastatic CRC sotorasib + EGFR + chemo combination). 15 ClinTrialFinder corpus trials.
Mirati / Bristol Myers Squibb's KRAS G12C covalent inhibitor. FDA-approved December 2022 for KRAS G12C NSCLC (post-platinum) based on KRYSTAL-1, and FDA accelerated approval June 2024 for KRAS G12C metastatic CRC in combination with cetuximab (KRYSTAL-1 CRC cohort) — that CRC indication was withdrawn September 1, 2026 after the confirmatory Phase 3 KRYSTAL-10 missed its PFS and OS endpoints. Current Phase 3: NCT06875310 (KRYSTAL-4, adagrasib + pembrolizumab + chemo vs placebo + chemo) + NCT04613596 (adagrasib monotherapy or + pembrolizumab in KRAS G12C NSCLC). Documented CNS penetration / intracranial activity is a clinical differentiator vs sotorasib. 7 ClinTrialFinder corpus trials. For drug-page detail, see /drugs/krazati.
Revolution Medicines's first-in-class pan-RAS RAS(ON) inhibitor, FDA-approved August 26, 2026 as RASONQUE for previously treated metastatic pancreatic adenocarcinoma (RASolute 302: median OS 13.2 vs 6.7 months vs chemotherapy, HR 0.40; EU CHMP positive opinion October 15, 2026) — binds the GTP-bound 'ON' state of multiple activated RAS isoforms (KRAS, NRAS, HRAS), spanning KRAS G12C + G12D + G12V + G12R + G13D + Q61 in a single molecule. This broadens the eligible patient population from ~13% of NSCLC (G12C only) to ~25-30% of NSCLC (all KRAS-mutant), ~40-50% of CRC, and 90%+ of pancreatic. Three further Phase 3 trials are recruiting: NCT06881784 (RASolve, 1L metastatic NSCLC), NCT07491445 (1L metastatic pancreatic + gemcitabine/nab-paclitaxel), NCT07252232 (adjuvant treatment for resected pancreatic ductal adenocarcinoma). Daraxonrasib is the most-cited drug page on CTF for ChatGPT live citations over the past 7 days — multiple residential-shape users in Eurasia, France, Croatia, Canada, and elsewhere have hit the drug page via ChatGPT citation. The class is generating substantial researcher and patient interest. 6 ClinTrialFinder corpus trials. For drug-page detail, see /drugs/daraxonrasib.
Three concurrent KRAS G12C Phase 3 programs aiming at the 1L NSCLC setting (vs sotorasib + adagrasib's 2L+ label). Olomorasib (Lilly): NCT06119581 1L olomorasib + pembrolizumab ± chemo. Divarasib (Genentech): NCT06793215 divarasib + pembrolizumab vs SoC + NCT07541170 vs investigator's choice chemo. Garsorasib (InventisBio): NCT06300177 garsorasib vs docetaxel in 2L+ NSCLC + NCT07174908 garsorasib + IN10018 FAK inhibitor combination. The 1L NSCLC G12C space is the most competitive battleground in KRAS development — multiple Phase 3 readouts expected over the next 12-18 months.
Merck's KRAS G12C inhibitor with two Phase 3 trials: NCT06345729 (calderasib + pembrolizumab in 1L NSCLC) and the unusually-positioned NCT07431827 (calderasib + pembrolizumab as ADJUVANT for completely-resected stage IIA-IIIB N2 KRAS G12C NSCLC). The adjuvant KRAS inhibitor concept is novel — aimed at preventing recurrence in resected early-stage disease, not treating advanced disease.
Jacobio's KRAS G12C inhibitor with the most-clinically-distinctive Phase 3 strategy: NCT06416410 glecirasib combined with JAB-3312 (an SHP2 inhibitor) as 1L treatment for KRAS G12C NSCLC. The dual-target combination strategy addresses the known KRAS feedback loop (KRAS inhibition triggers MAPK reactivation via RTK/SHP2), and is the only Phase 3 KRAS G12C + SHP2 combination program in the class.
The KRAS G12D inhibitor class addresses the most common KRAS mutation in pancreatic (~40%) and a major CRC subset (~10%). Five investigational small-molecule G12D inhibitors are in development: Zoldonrasib (RMC-9805, Revolution Medicines) — Phase 3 NCT07621718 (chemo combo); MRTX1133 (Mirati/BMS) — Phase 1/2 in pancreatic + CRC; HRS-4642 (Hengrui) — largest Chinese G12D program (11 trials); VS-7375 (Verastem) — Phase 1/2; INCB161734 (Incyte) — Phase 3 NCT07522073. Setidegrasib (ASP3082, Astellas) is mechanistically distinct — a KRAS G12D PROTAC-like degrader that triggers proteasomal degradation of mutant KRAS protein rather than inhibiting its function. Setidegrasib has Phase 3 NCT07566052 (vs docetaxel in NSCLC) + NCT07409272 (chemo combo). The G12D wave addresses a roughly 3-4x larger pancreatic and CRC patient population than G12C.
NIH/NCI's engineered T-cell receptor (TCR) cell therapy targeting the KRAS G12V mutant peptide presented by HLA-A*11:01. Patient T cells are engineered ex-vivo to express a TCR that recognizes the KRAS G12V × HLA-A*11:01 complex on tumor cell surface, then re-infused. Mechanistically distinct from small-molecule KRAS inhibitors — instead of binding mutant KRAS protein directly, TCR cells recognize and kill cells displaying the mutant peptide on their HLA surface. Eligibility requires BOTH (a) confirmed KRAS G12V mutation on tumor tissue, and (b) HLA-A*11:01 typing (HLA-A*11:01 is more prevalent in East Asian populations ~30-40% than Western populations ~10-15%). The KRAS G12V mutation is most common in pancreatic adenocarcinoma (~25-30%). This is the trial the Task 332 Egyptian pancreatic patient examined three separate times across 24 hours — representing the most-engaged trial drill-down of the past 7 days.
The 100 recruiting (and 28 not-yet-recruiting) KRAS inhibitor trials are grouped by primary cancer type below. KRAS mutation testing on tumor tissue or ctDNA is required upfront — the exact mutation matters (G12C, G12D, G12V, etc.) because different drugs target different mutations.
KRAS G12C NSCLC is the largest and most competitive KRAS-targeted setting. Sotorasib + adagrasib are FDA-approved 2L+; 5+ challenger Phase 3 trials are aiming at the 1L position.
The Revolution Medicines pan-RAS Phase 3 program addresses cancer types where most patients are NOT G12C (pancreatic 90%+ KRAS, mostly G12D + G12V + G12R).
Newer pan-KRAS inhibitors list exactly which mutations they accept, and KRAS G12R (~15% of pancreatic cancer) is often left out. As of October 2026, two pan-KRAS trials list their allowed mutations without G12R:
Patients with G12R can look instead at pan-RAS(ON) daraxonrasib (FDA-approved August 2026 for previously treated metastatic pancreatic cancer, and the RASolute trials above), ASP5834 (NCT07094204, G12R listed) and PT0511 (NCT07300150, any KRAS mutation). The pancreatic cancer page lists G12R and G12V options in full.
Sotorasib + panitumumab is FDA-approved for previously treated KRAS G12C metastatic CRC (January 2025, CodeBreaK 300). Adagrasib + cetuximab (June 2024 accelerated approval) was withdrawn September 1, 2026 after the confirmatory Phase 3 KRYSTAL-10 missed its PFS and OS endpoints. The next-line confirmatory trials test alternative EGFR + chemo combinations.
Showing 100 RECRUITING + 28 not-yet-recruiting KRAS inhibitor interventional trials in the ClinTrialFinder corpus as of June 21, 2026 (23 Phase 3 across the class). Trials enrolling patients without KRAS mutation testing requirement are out of scope. For the latest searches: sotorasib, adagrasib, daraxonrasib, KRAS G12C, KRAS G12D.
| Class | Target State | FDA Approvals | Eligible Population |
|---|---|---|---|
| KRAS G12C 'OFF' (this hub) | GDP-bound inactive state | Sotorasib (Lumakras, 2021 NSCLC + 2025 CRC with panitumumab), Adagrasib (Krazati, 2022 NSCLC; 2024 CRC indication withdrawn 2026) | ~13% of NSCLC, ~3-4% of CRC. Sub-population — relatively small absolute patient count. |
| Pan-RAS 'ON' (daraxonrasib) | GTP-bound active state, multiple isoforms | Daraxonrasib (RASONQUE, Aug 2026, previously treated metastatic pancreatic cancer) | ~25-30% of NSCLC (all KRAS-mut), ~40-50% of CRC, 90%+ of pancreatic. ~3-4x larger pancreatic + CRC absolute count vs G12C. |
| KRAS G12D (small molecule) | Covalent binding at G12D aspartic acid | Investigational | ~20% of pancreatic + ~10% of CRC + ~3% of NSCLC. Largest pancreatic target. |
| KRAS G12D degrader (setidegrasib) | PROTAC-like protein degradation | Investigational | Same KRAS G12D population as above. |
| KRAS G12V TCR cell therapy | HLA-A*11:01 × G12V peptide complex on cell surface | Investigational | KRAS G12V (~25-30% pancreatic) AND HLA-A*11:01+ (10-15% Western, 30-40% East Asian). Significantly smaller eligible population due to HLA restriction. |
How KRAS inhibitors are positioned in practice. Sotorasib + adagrasib are FDA-approved for KRAS G12C-confirmed NSCLC (2L+) and KRAS G12C CRC (sotorasib + panitumumab, 2L+; the adagrasib + cetuximab CRC indication was withdrawn in September 2026); pan-RAS daraxonrasib (RASONQUE) is FDA-approved for previously treated metastatic pancreatic adenocarcinoma regardless of RAS variant (August 2026). The clinical decision tree starts with KRAS mutation testing: if G12C-positive, FDA-approved sotorasib or adagrasib first. If pancreatic and previously treated, daraxonrasib is an approved option; in first line or for G12D-specific agents the pathway is investigational (daraxonrasib 1L Phase 3, zoldonrasib, HRS-4642, setidegrasib, MRTX1133, VS-7375, INCB161734). If G12V + pancreatic AND HLA-A*11:01+, the NCT04146298 TCR cell therapy is an additional option. Beyond its approved pancreatic indication, daraxonrasib is in Phase 3 in 1L NSCLC and 1L / adjuvant pancreatic cancer — potentially the broadest KRAS-targeted option if those trials read out positively. Cross-trial efficacy comparisons absent randomized data are not reliable.
What is a KRAS inhibitor?
KRAS is the most frequently mutated oncogene in human cancer — ~25-30% of NSCLC adenocarcinoma, ~40-50% of CRC, and 90%+ of pancreatic ductal adenocarcinoma. KRAS was considered 'undruggable' for decades until covalent KRAS G12C inhibitors were discovered. Sotorasib (Lumakras) was FDA-approved May 2021 — the first KRAS-targeted oral small molecule. Adagrasib (Krazati) followed December 2022 for NSCLC; its June 2024 KRAS G12C CRC + cetuximab indication was withdrawn in September 2026 after KRYSTAL-10 missed its endpoints. KRAS G12D inhibitors and pan-RAS RAS(ON) agents are the next wave.
Is sotorasib (Lumakras) or adagrasib (Krazati) approved for my cancer?
Sotorasib (Lumakras, Amgen): FDA May 2021 for KRAS G12C NSCLC after at least one prior systemic therapy. Adagrasib (Krazati, Mirati/BMS): FDA Dec 2022 for KRAS G12C NSCLC; its Jun 2024 KRAS G12C CRC + cetuximab indication was withdrawn Sep 1, 2026 (KRYSTAL-10 missed PFS/OS). Sotorasib + panitumumab: FDA Jan 2025 for KRAS G12C CRC (CodeBreaK 300). Both require KRAS G12C-mutation testing. Daraxonrasib (RASONQUE): FDA Aug 26, 2026 for metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, any RAS variant (RASolute 302, OS 13.2 vs 6.7 months); EU CHMP positive opinion Oct 15, 2026. Garsorasib and glecirasib are NMPA-approved in China for previously treated KRAS G12C NSCLC (not FDA-approved). The other KRAS inhibitors are all investigational. Consult current FDA prescribing information.
What is daraxonrasib and how is pan-RAS different from KRAS G12C?
Daraxonrasib (RMC-6236, Revolution Medicines) is a 'pan-RAS' inhibitor targeting the GTP-bound 'ON' state of multiple activated RAS isoforms simultaneously (KRAS G12C + G12D + G12V + G12R + G13D + Q61 + NRAS + HRAS). Sotorasib + adagrasib target only the GDP-bound 'OFF' state of G12C specifically. Pan-RAS broadens the eligible patient population from ~13% of NSCLC (G12C) to ~25-30% of NSCLC (all KRAS) and 90%+ of pancreatic. Daraxonrasib was FDA-approved in August 2026 (as RASONQUE) for previously treated metastatic pancreatic adenocarcinoma, and has three further Phase 3 trials: RASolve in 1L NSCLC, 1L pancreatic + GnP, and resected pancreatic adjuvant. For drug-page detail, see /drugs/daraxonrasib.
What KRAS G12D inhibitors are available in clinical trials?
KRAS G12D is the most common KRAS mutation in pancreatic (~20%). Multiple investigational agents: Zoldonrasib (RMC-9805) RAS(ON) Ph3. MRTX1133 covalent Ph1/2. Setidegrasib (ASP3082) PROTAC-like DEGRADER Ph3. HRS-4642 (Hengrui) largest Chinese program (11 trials). VS-7375 (Verastem), INCB161734 (Incyte) Ph3.
What about cell therapy for KRAS-mutant cancer?
KRAS G12V TCR cell therapy (NCT04146298) — engineered patient T cells expressing a TCR recognizing the KRAS G12V mutant peptide presented by HLA-A*11:01. Requires KRAS G12V confirmation AND HLA-A*11:01 testing (more common in East Asian populations ~30-40% than Western ~10-15%). KRAS G12V is ~25-30% of pancreatic.
How do I find a KRAS inhibitor trial that fits my situation?
Use ClinTrialFinder's AI-powered matching based on cancer type (NSCLC / CRC / pancreatic), exact KRAS mutation (G12C, G12D, G12V, G12R, G13D, Q61, KRAS amplification), HLA-A*11:01 status (for KRAS G12V TCR), prior IO/KRAS G12C inhibitor exposure, line of therapy. Request molecular testing including KRAS mutation type + comprehensive genomic profiling. For drug-page detail, see /drugs/daraxonrasib. For broader disease landscapes: /trials/lung-cancer-nsclc, /trials/colorectal-cancer, /trials/pancreatic-cancer.
Find Matching KRAS Inhibitor Trials
Use ClinTrialFinder's AI-powered matching to find sotorasib (Lumakras), adagrasib (Krazati), daraxonrasib, divarasib, olomorasib, garsorasib, glecirasib, calderasib, zoldonrasib, setidegrasib, MRTX1133, HRS-4642, VS-7375, INCB161734, and KRAS G12V TCR trials based on your cancer type, exact KRAS mutation, prior therapy, and country.
Find Matching KRAS Inhibitor TrialsThis page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your medical oncologist. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here. FDA approval dates and indications are summarized for context only; consult the current FDA prescribing information for each drug for authoritative regulatory status.