marked.bio

KRAS G12C inhibitor (OFF state) · small molecule

sotorasib

21 active trials across 5 of our biomarkers, targeting KRAS G12C. 3 active approvals for a biomarker on marked.bio.

Also known as AMG 510, Lumakras, Lumykras.

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
sotorasib
FDA, 2021
advanced, after >=1 prior systemic therapy Still accelerated: current label carries the accelerated-approval statement and FDA lists it under Ongoing accelerated approvals (AA 28/05/2021). A 2023 complete response letter on conversion is reported by the company; not verified from an FDA source. Source
EU (EMA), 2022
advanced, progressed after >=1 prior systemic therapy EC conditional MA 06/01/2022. No colorectal indication in the EU (EPAR indication checked). Source
Lumakras, Lumykras 		KRAS G12C NSCLC Approved 2021 accelerated Approved 2022 conditional

In the US label

CodeBreaK 100 single-arm, 124 patients
Response 36% (28-45)Lasting 10 months

Serious side effects 50%Stopped for side effects 9%Fatal 3.4%

Trial details and side effects
Patients
KRAS G12C NSCLC after at least 1 prior systemic therapy (NCT03600883)
Most common side effects
diarrhoea 42%, musculoskeletal pain 35%, nausea 26%, fatigue 26%, hepatotoxicity 25%, cough 20% (204 patients)
Later trial
CodeBreaK 200 vs docetaxel (171 vs 174 patients): median PFS 5.6 vs 4.5 months, HR 0.66 (95% CI 0.51-0.86); ORR 28% vs 13%; not powered for OS. Published trial result, not in the US label.
Notes
US label rev. 01/2025, sections 6 and 14. Accelerated approval based on ORR and DOR.
Source
US label

In the EU product information

CodeBreaK 100 single-arm, 124 patients
Response 37% (29-46)Lasting 11.1 months

Trial details and side effects
Patients
KRAS G12C NSCLC after at least 1 prior systemic therapy (NCT03600883)
Most common side effects
diarrhoea 42%, musculoskeletal pain 35%, nausea 26%, fatigue 26%, hepatotoxicity 25%, cough 20% (204 patients)
Notes
EU SmPC section 5.1: CodeBreaK 100 only (conditional authorisation; CodeBreaK 200 appears in the safety section only). Side effects from the US label.
Source
EU product information
sotorasib with panitumumab
FDA, 2025
metastatic, after fluoropyrimidine/oxaliplatin/irinotecan chemotherapy FDA approval 16/01/2025 (regular; no accelerated-approval statement on the current label). Source
Lumakraspanitumumab page 		KRAS G12C colorectal Approved 2025 Not approved

CodeBreaK 300 vs trifluridine/tipiracil or regorafenib (investigator's choice), 53 vs 54 patients
PFS 5.6 months vs 2.0 months, HR 0.48 (0.30-0.78)Response 26% vs 0%OS not reached vs 10.3 months, HR 0.70 (0.41-1.18), not significant

Serious side effects 26%Stopped for side effects 2% (1 patient)Fatal 4.3%

Trial details and side effects
Patients
KRAS G12C metastatic colorectal cancer after fluoropyrimidine, oxaliplatin and irinotecan (NCT05198934)
Most common side effects
rash 87%, dry skin 28%, diarrhoea 28%, stomatitis 26%, fatigue 21%, musculoskeletal pain 21% (47 patients)
Notes
US label rev. 01/2025, sections 6 and 14. Sotorasib 960 mg with panitumumab.
Source
US label

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
KRAS G12C 20 42 Phase 3
EGFR exon 19 deletion / L858R 1 2 Phase 1
KRAS G12D 1 2 Phase 2
MSI-H / dMMR 1 1 Phase 2
BRAF V600E 0 1 –

Sponsors

Industry sponsors leading active biomarker-selected trials of sotorasib.

  1. Amgen 4
  2. Bayer 1
  3. Roche 1
  4. Orion Pharma 1
  5. Verastem 1

Trials

21 of 43 trials shown

  1. Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-naïve Participants With Metastatic Colorectal Cancer With KRAS p.G12C Mutation

    Recruiting Phase 3 Amgen Started 2024Primary completion 2028-09 NCT06252649

    FOLFIRIsotorasib FDA EUpanitumumab FDAbevacizumab

    Pathologically documented metastatic colorectal adenocarcinoma with KRAS p.G12C mutation by a locally validated assay.

    KRAS G12CMetastatic Colorectal Cancer

  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. A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)

    Recruiting Phase 3 Amgen Started 2023Primary completion 2027-06 NCT05920356

    sotorasib FDA EUpembrolizumab

    G12C mutation and negative for PD-L1 expression by central testing or local laboratory testing…

    KRAS G12CNon-Small Cell Lung Cancer (NSCLC)

  4. Sotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation

    Recruiting Phase 1/2 National Cancer Institute (NCI) Started 2026Primary completion 2027-06 NCT07012031

    sotorasib FDA EUtrastuzumab deruxtecan

    …must have histologically or cytologically documented locally advanced or metastatic KRAS\^G12C-mutant NSCLC that has previously been treated with a KRAS\^G12C inhibitor AND an immune c…

    KRAS G12CLocally Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8

  5. 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

  6. A 2-part Phase 1/2 Open-label Trial on ODM-212

    Recruiting Phase 1/2 Orion Pharma Started 2026Primary completion 2029-09 NCT07563738

    ODM-212ipilimumabnivolumabgemcitabinenab-paclitaxelsotorasib FDA EU

    …ically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC and a KRAS G12C mutation, confirmed using a validated test, who have documented progression on a prior KR…

    KRAS G12CMesothelioma, Pancreatic Cancer, NSCLC (Advanced Non-small Cell Lung Cancer)

  7. 5-fluorouracil Plus Panitumumab (Anti-EGFR) and Sotorasib (KRAS G12C Inhibitor) in First-line Treatment of Patients Non-eligible for a Doublet/Triplet Chemotherapy With Advanced Unresectab

    Not yet recruiting Phase 2 Federation Francophone de Cancerologie Digestive Started 2025Primary completion 2030-06 NCT07124884

    sotorasib FDA EUpanitumumab FDAfluorouracil

    Proven KRAS G12C mutation as locally assessed by means of an IVDR-compliant test

    KRAS G12CColorectal Carcinoma, KRAS G12C Mutation, Unresectable Colorectal Cancer

  8. Testing the Use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial)

    Active, not recruiting Phase 2 National Cancer Institute (NCI) Started 2024Primary completion 2028-12 NCT05638295

    panitumumab FDAsotorasib FDA EU

    Patient must have a KRAS G12C alteration as determined by the ComboMATCH screening assessment

    KRAS G12CAdvanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm

  9. A Study of Sotorasib in People With Non-Small Cell Lung Cancer

    Recruiting Phase 2 Memorial Sloan Kettering Cancer Center Started 2024Primary completion 2027-08 NCT06582771

    sotorasib FDA EU

    KRAS G12C mutation on prior tumor biopsy or cell-free DNA (cfDNA) testing

    KRAS G12CNon Small Lung Cancer

  10. Pre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN)

    Recruiting Phase 2 Gruppo Oncologico del Nord-Ovest Started 2023Primary completion 2027-05 NCT05845450

    trastuzumab deruxtecandurvalumabpanitumumab FDAbotensilimabbalstilimabsotorasib FDA EUVorbipiprantnivolumabamivantamab

    COHORT 8: pMMR/MSS status and KRAS G12C mutation, absence of HER2 overexpression/amplification and wild-type status for BRAF.

    KRAS G12CMSI-H / dMMRColorectal Cancer, Resectable Colorectal Carcinoma

  11. Sotorasib in Previously Treated Locally Advanced or Metastatic NSCLC Subjects With Mutated KRAS p.G12C

    Recruiting Phase 2 Gustave Roussy, Cancer Campus, Grand Paris Started 2022Primary completion 2027-12 NCT05631249

    sotorasib FDA EU

    …ocumented, previously treated, locally-advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation confirmed through molecular testing (results of both tissue and liquid biopsy ar…

    KRAS G12CKRAS P.G12C, Non Small Cell Lung Cancer

  12. Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients

    Active, not recruiting Phase 1/2 Verastem Started 2022Primary completion 2026-06 NCT05074810

    avutometinib FDAsotorasib FDA EUdefactinib FDA

    Known KRAS G12C mutation

    KRAS G12CNon Small Cell Lung Cancer, KRAS Activating Mutation

  13. Clinical Trial of AMG510 in Stage III Unresectable NSCLC KRAS p.G12C Patients and Ineligible for Chemo-radiotherapy

    Recruiting Phase 2 Fundación GECP Started 2022Primary completion 2027-12 NCT05398094

    sotorasib FDA EU

    Patients who have documentation of KRAS p.G12C prior to enrollment.

    KRAS G12CNon-small Cell Lung Cancer Stage III, KRAS P.G12C

  14. A Phase II Study of Neoadjuvant Sotorasib in Combination With Cisplatin or Carboplatin and Pemetrexed for Surgically Resectable Stage IIA-IIIB Non-Squamous Non-Small Cell Lung Cancer With a KRAS p.G12C Mutation

    Active, not recruiting Phase 2 M.D. Anderson Cancer Center Started 2022Primary completion 2027-10 NCT05118854

    sotorasib FDA EUcisplatincarboplatinpemetrexed

    Identification of a KRAS p.G12C mutation in tumor tissue or plasma by an approved diagnostic device for detection of KRAS…

    KRAS G12CKRAS G12DLung Cancer

  15. Testing the Use of Targeted Treatment (AMG 510) for KRAS G12C Mutated Advanced Non-squamous Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial)

    Active, not recruiting Phase 2 SWOG Cancer Research Network Started 2021Primary completion 2026-12 NCT04625647

    sotorasib FDA EU

    Biomarker eligibility for S1900E is based on the identification of a KRAS\^G12C mutation

    KRAS G12CLung Adenocarcinoma, Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Squamous Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8

  16. A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-159642 in Participants With Advanced Solid Tumors

    Recruiting Phase 1 Bayer Started 2025Primary completion 2027-08 NCT06804824

    VVD-159642sotorasibtrametinib

    any solid tumor that harbors an epidermal growth factor receptor (EGFR) alteration as per local/historical testing

    EGFR exon 19 deletion / L858RAdvanced Solid Tumors

  17. Sotorasib Combined With First-line Chemotherapy for Advanced Pancreatic Adenocarcinoma

    Recruiting Phase 1 Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) Started 2025Primary completion 2030-08 NCT06892054

    sotorasib FDA EU

    …med treatment-naïve of locally advanced or metastatic pancreatic adenocarcinoma harboring KRAS p.G12C mutation assessed by means of a IVDR compliant test) 5) Measurable disease per RECIST 1.1…

    KRAS G12CPancreatic Adenocarcinoma

  18. Carfilzomib in Combination With Sotorasib for the Treatment of Patients With KRAS G12C Mutated Advanced or Metastatic Non-small Cell Lung Cancer

    Recruiting Phase 1 City of Hope Medical Center Started 2024Primary completion 2026-11 NCT06249282

    Carfilzomibsotorasib FDA EU

    The tumor must exhibit evidence of KRASG12C mutation which is determined by either a Clinical Laboratory Improvement Act (CLIA) certi…

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

  19. Anvumetostat Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104).

    Active, not recruiting Phase 1 Amgen Started 2024Primary completion 2026-10 NCT06333951

    Anvumetostatcarboplatinpaclitaxelpembrolizumabpemetrexedsotorasib FDA EU

    Subprotocol B - Histologically confirmed NSCLC with homozygous MTAP-deletion and KRAS p.G12C mutation.

    KRAS G12CThoracic Tumors, Non-small Cell Lung Cancer

  20. Ladarixin With Sotorasib in Advanced NSCLC

    Recruiting Phase 1 NYU Langone Health Started 2023Primary completion 2027-08 NCT05815173

    sotorasib FDA EULadarixin

    Patients must have documentation of presence of KRASG12C mutation in tumor tissue.

    KRAS G12CAdvanced Non-small Cell Lung Cancer With KRAS G12C Mutation

  21. Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)

    Active, not recruiting Phase 1 Amgen Started 2019Primary completion 2026-12 NCT04185883

    sotorasib FDA EUtrametinibvociprotafibafatinibpembrolizumabpanitumumab FDAcarboplatinpemetrexeddocetaxelpaclitaxelatezolizumabpalbociclib

    Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing performed according to in-country requireme…

    KRAS G12CAdvanced Solid Tumors, Kirsten Rat Sarcoma (KRAS) pG12C Mutation