marked.bio

KRAS G12C inhibitor (OFF state) · small molecule

adagrasib

17 active trials across 4 of our biomarkers, targeting KRAS G12C. 2 active approvals for a biomarker on marked.bio.

Also known as MRTX849, Krazati.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

TherapyBiomarkerTumourUnited StatesEuropean Union
adagrasib
FDA, 2022
locally advanced or metastatic, after >=1 prior systemic therapy AA 12/12/2022; still listed under FDA Ongoing accelerated approvals. Source
EU (EMA), 2024
advanced, progressed after >=1 prior systemic therapy Conditional MA, EC decision 05/01/2024 (EMA medicines data). An initial negative CHMP opinion and re-examination are reported in news; not verified against an EMA document. No colorectal indication in the EU. Source
Krazati 		KRAS G12C NSCLC Approved 2022 accelerated Approved 2024 conditional

In the US label

KRYSTAL-1 single-arm, 112 patients
Response 43% (34-53)Lasting 8.5 months

Serious side effects 57%Stopped for side effects 13%Fatal 11%

Trial details and side effects
Patients
KRAS G12C NSCLC after platinum chemotherapy and a checkpoint inhibitor (NCT03785249)
Most common side effects
diarrhoea 70%, nausea 69%, fatigue 59%, vomiting 56%, musculoskeletal pain 41%, hepatotoxicity 37% (116 patients)
Later trial
KRYSTAL-12 vs docetaxel (298 vs 140 patients): median PFS 5.5 vs 3.8 months, HR 0.58 (95% CI 0.45-0.76); ORR 32% vs 9%. Published trial result, not in the US label.
Notes
US label rev. 08/2026, sections 6 and 14. Still accelerated approval based on ORR and DOR.
Source
US label

In the EU product information

KRYSTAL-1 single-arm, 116 patients
Response 41% (32-51)Lasting 8.5 months

Trial details and side effects
Patients
KRAS G12C NSCLC after platinum chemotherapy and a checkpoint inhibitor (NCT03785249)
Most common side effects
diarrhoea 70%, nausea 69%, fatigue 59%, vomiting 56%, musculoskeletal pain 41%, hepatotoxicity 37% (116 patients)
Notes
EU SmPC section 5.1: KRYSTAL-1 cohort A (conditional authorisation; KRYSTAL-12 final report due 2027). Side effects from the US label.
Source
EU product information
adagrasib with cetuximab
FDA, 2024
locally advanced or metastatic, previously treated AA 21/06/2024; withdrawn 01/09/2026 per FDA 'Withdrawn cancer accelerated approvals' page. The DailyMed label (revised 3/2026) still shows the CRC indication; not yet updated. Reason for withdrawal not stated on the FDA page. Source
Krazaticetuximab page 		KRAS G12C colorectal Withdrawn approved 2024 Not approved

KRYSTAL-1 (colorectal cohort) single-arm, 94 patients
Response 34% (25-45)Lasting 5.8 months

Serious side effects 30%Stopped for side effects 2% (2 patients, adagrasib)Fatal 1% (1 patient)

Trial details and side effects
Patients
KRAS G12C colorectal cancer, previously treated (NCT03785249)
Most common side effects
rash 84%, nausea 68%, diarrhoea 65%, vomiting 57%, fatigue 57%, musculoskeletal pain 47% (94 patients)
Notes
Adagrasib with cetuximab. From the earlier 2026 US label; the indication was removed from the label in 08/2026.
Source
US label

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
KRAS G12C 17 31 Phase 3
BRAF V600E 1 2 Phase 2
KRAS G12D 1 3 Phase 1
EGFR exon 19 deletion / L858R 0 1 –

Sponsors

Industry sponsors leading active biomarker-selected trials of adagrasib.

  1. Bristol Myers Squibb 8
  2. Roche 1
  3. Kura Oncology 1

Trials

17 of 31 trials shown

  1. A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

    Recruiting Phase 3 Bristol Myers Squibb Started 2025Primary completion 2029-09 NCT06875310

    adagrasib FDA EUpembrolizumabcarboplatinpemetrexedcisplatin

    …istologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor sample and/or circulating tumor deoxyribonucleic acid (ctDNA).

    KRAS G12CCarcinoma, Non-Small-Cell Lung

  2. A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer

    Active, not recruiting Phase 3 Roche Started 2024Primary completion 2026-05 NCT06497556

    divarasibsotorasib FDA EUadagrasib FDA EU

    Documentation of the presence of a KRAS G12C mutation

    KRAS G12CNon-Small Cell Lung Cancer, KRAS G12C Lung Cancer

  3. Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10)

    Active, not recruiting Phase 3 Bristol Myers Squibb Started 2021Primary completion 2026-01 NCT04793958

    adagrasib FDA EUcetuximabmFOLFOX6FOLFIRI

    Histologically confirmed diagnosis of colorectal carcinoma with KRAS G12C mutation in tumor tissue.

    KRAS G12CAdvanced Colorectal Cancer, Metastatic Colorectal Cancer

  4. Phase 3 Study of MRTX849 (Adagrasib) vs Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

    Active, not recruiting Phase 3 Bristol Myers Squibb Started 2021Primary completion 2023-12 NCT04685135

    adagrasib FDA EUdocetaxel

    Histologically or cytologically confirmed diagnosis of NSCLC with KRAS G12C mutation.

    KRAS G12CMetastatic Non Small Cell Lung Cancer, Advanced Non Small Cell Lung Cancer

  5. Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G12C Mutation KRYSTAL-7

    Recruiting Phase 2/3 Bristol Myers Squibb Started 2020Primary completion 2028-10 NCT04613596

    adagrasib FDA EUpembrolizumab

    Phase 2: Histologically confirmed diagnosis of unresectable or metastatic NSCLC with KRAS G12C mutation and any PD-L1 TPS

    KRAS G12CAdvanced Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer

  6. CIMAvax-EGF With KRAS G12C Inhibitor for the Treatment of Advanced, KRAS G12C Mutated Non Small Cell Lung Cancer

    Not yet recruiting Phase 2 Roswell Park Cancer Institute Started 2026Primary completion 2029-06 NCT07543172

    adagrasib FDA EURecombinant Human EGF-rP64K/Montanide ISA 51 Vaccinesotorasib FDA EU

    Documented KRAS G12C mutation.

    KRAS G12CAdvanced Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8

  7. Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)

    Active, not recruiting Phase 2 Bristol Myers Squibb Started 2024Primary completion 2026-10 NCT05853575

    adagrasib FDA EU

    …CLC (NSCLC that started in the lungs and then spread to other parts of the body) with the KRAS G12C mutation.

    KRAS G12CAdvanced Cancer, Metastatic Cancer, Malignant Neoplasm of Lung

  8. A Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations

    Recruiting Phase 1/2 M.D. Anderson Cancer Center Started 2024Primary completion 2029-03 NCT06412198

    cetuximabcemiplimabadagrasib FDA EU

    …y confirmed diagnosis of advanced/metastatic microsatellite stable colorectal cancer with KRASG12C mutation with 1+ prior line(s) of therapy

    KRAS G12CMetastatic Colorectal Cancer, KRAS G12C Mutations

  9. Adagrasib + SRS for Patients With Metastatic KRAS G12C-mutated NSCLC With Untreated Brain Metastases

    Recruiting Phase 2 Ryan Gentzler, MD Started 2024Primary completion 2027-02 NCT06248606

    adagrasib FDA EU

    Known to have a KRAS G12C mutation.

    KRAS G12CNon Small Cell Lung Cancer, NSCLC, KRAS G12C

  10. Adagrasib in Patients With KRASG12C-mutant NSCLC Who Are Elderly or Have Poor Performance Status

    Active, not recruiting Phase 2 ETOP IBCSG Partners Foundation Started 2023Primary completion 2025-07 NCT05673187

    adagrasib FDA EU

    KRASG12C-mutation by local testing (by tissue or ctDNA).

    KRAS G12CNSCLC Stage IV, KRAS P.G12C

  11. Combination Therapies With Adagrasib in Patients With Advanced NSCLC With KRAS G12C Mutation

    Active, not recruiting Phase 2 Bristol Myers Squibb Started 2022Primary completion 2026-09 NCT05609578

    adagrasib FDA EUpembrolizumabpemetrexedcisplatincarboplatin

    … unresectable or metastatic NSCLC with histologically confirmed (squamous or nonsquamous) KRASG12C mutation and histologically confirmed PD-L1 TPS ≥1%.

    KRAS G12CAdvanced NSCLC, Metastatic Lung Cancer

  12. Genetic Testing in Guiding Treatment for Patients With Brain Metastases

    Active, not recruiting Phase 2 Alliance for Clinical Trials in Oncology Started 2019Primary completion 2025-11 NCT03994796

    abemaciclibpaxalisibentrectinibadagrasib FDA EU

    Similarly, for patients with KRAS G12C mutations, MRTX849 may be used for newly diagnosed brain metastases.

    KRAS G12CBRAF V600ECDK Gene Mutation, Metastatic Malignant Neoplasm in the Brain, Metastatic Malignant Solid Neoplasm, NTRK Family Gene Mutation

  13. Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1

    Active, not recruiting Phase 1/2 Bristol Myers Squibb Started 2019Primary completion 2026-06 NCT03785249

    adagrasib FDA EUpembrolizumabcetuximabafatinib

    Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation

    KRAS G12CAdvanced Cancer, Metastatic Cancer, Malignant Neoplastic Disease

  14. Phase 1 Study Of Izalontamab Brengitecan + Adagrasib In NSCLC - The IZA-A Trial

    Recruiting Phase 1 M.D. Anderson Cancer Center Started 2026Primary completion 2027-12 NCT07382726

    adagrasib FDA EUizalontamab brengitecan

    Tumor must harbor a KRAS G12C mutation.

    KRAS G12CNon-small Cell Lung Cancer

  15. A Study of BMS-986488 as Monotherapy and Combination Therapy in Participants With Advanced Malignant Tumors

    Recruiting Phase 1 Bristol Myers Squibb Started 2025Primary completion 2027-10 NCT06764771

    BMS-986488adagrasib FDA EUcetuximabnivolumab

    i) Part 1B: solid tumors with KRAS G12C mutation.

    KRAS G12CAdvanced Malignant Tumors

  16. Phase I Trial of Adagrasib (MRTX849) in Combination With Cetuximab and Irinotecan in Patients With Colorectal Cancer

    Active, not recruiting Phase 1 M.D. Anderson Cancer Center Started 2023Primary completion 2027-09 NCT05722327

    adagrasib FDA EUirinotecancetuximab

    Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum with KRASG12C mutation.

    KRAS G12CColon Cancer, Colorectal Cancer

  17. KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

    Recruiting Phase 1 Kura Oncology Started 2023Primary completion 2027-01 NCT06026410

    Darlifarnibcabozantinibadagrasib FDA EU

    …eceived at least 1 prior systemic therapy including available approved SOC treatments for KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC.

    KRAS G12CKRAS G12DSolid Tumors With HRAS Alterations, Non Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC)