Clinical trial · Interventional
Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1
A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1
NCT03785249CI-TRIAL-00119666active not recruitingPhase 1 / Phase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced Cancer | Malignant Neoplasm | CURATED_BROADER | 0.78 |
| Malignant Neoplastic Disease | Malignant Neoplasm | ALIAS | 0.90 |
| Metastatic Cancer | Malignant Neoplasm | CURATED_BROADER | 0.78 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Afatinib | Drug | Afatinib | ALIAS |
| Cetuximab | Drug | Cetuximab | ALIAS |
| MRTX849 | Drug | Adagrasib | ALIAS |
| Pembrolizumab | Drug | Pembrolizumab | ALIAS |
Design
Arms and outcomes
Arms (9)
- type
- EXPERIMENTAL
- label
- Phase 1 Dose Exploration
- description
- Dose escalation of MRTX849 to determine maximum tolerated dose
- interventionNames
- Drug: MRTX849
- type
- EXPERIMENTAL
- label
- Phase 1b Expansion
- description
- Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens
- interventionNames
- Drug: MRTX849
- type
- EXPERIMENTAL
- label
- Phase 2
- description
- Separate cohorts of patients stratified by histological diagnosis, prior treatment history or co-mutation status (e.g., STK11) for evaluation of clinical activity of MRTX849
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation * Unresectable or metastatic disease * Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts * Adequate organ function Exclusion Criteria: * History of intestinal disease or major gastric surgery or inability to swallow oral medications * Other active cancer
References
Publications (7)
- DERIVEDNegrao MV, Spira AI, Heist RS, Janne PA, Pacheco JM, Weiss J, Gadgeel SM, Velastegui K, Yang W, Der-Torossian H, Christensen JG, Sabari JK. Intracranial Efficacy of Adagrasib in Patients From the KRYSTAL-1 Trial With KRASG12C-Mutated Non-Small-Cell Lung Cancer Who Have Untreated CNS Metastases. J Clin Oncol. 2023 Oct 1;41(28):4472-4477. doi: 10.1200/JCO.23.00046. Epub 2023 Jun 16. PMID 37327468
- DERIVEDBekaii-Saab TS, Yaeger R, Spira AI, Pelster MS, Sabari JK, Hafez N, Barve M, Velastegui K, Yan X, Shetty A, Der-Torossian H, Pant S. Adagrasib in Advanced Solid Tumors Harboring a KRASG12C Mutation. J Clin Oncol. 2023 Sep 1;41(25):4097-4106. doi: 10.1200/JCO.23.00434. Epub 2023 Apr 26. PMID 37099736
- DERIVEDYaeger R, Weiss J, Pelster MS, Spira AI, Barve M, Ou SI, Leal TA, Bekaii-Saab TS, Paweletz CP, Heavey GA, Christensen JG, Velastegui K, Kheoh T, Der-Torossian H, Klempner SJ. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Jan 5;388(1):44-54. doi: 10.1056/NEJMoa2212419. Epub 2022 Dec 21. PMID 36546659
- DERIVEDJanne PA, Riely GJ, Gadgeel SM, Heist RS, Ou SI, Pacheco JM, Johnson ML, Sabari JK, Leventakos K, Yau E, Bazhenova L, Negrao MV, Pennell NA, Zhang J, Anderes K, Der-Torossian H, Kheoh T, Velastegui K, Yan X, Christensen JG, Chao RC, Spira AI. Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRASG12C Mutation. N Engl J Med. 2022 Jul 14;387(2):120-131. doi: 10.1056/NEJMoa2204619. Epub 2022 Jun 3. PMID 35658005
- DERIVEDSabari JK, Velcheti V, Shimizu K, Strickland MR, Heist RS, Singh M, Nayyar N, Giobbie-Hurder A, Digumarthy SR, Gainor JF, Rajan AP, Nieblas-Bedolla E, Burns AC, Hallin J, Olson P, Christensen JG, Kurz SC, Brastianos PK, Wakimoto H. Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data from Patients with KRASG12C-Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2022 Aug 2;28(15):3318-3328. doi: 10.1158/1078-0432.CCR-22-0383. PMID 35404402
- Ou SI, Janne PA, Leal TA, Rybkin II, Sabari JK, Barve MA, Bazhenova L, Johnson ML, Velastegui KL, Cilliers C, Christensen JG, Yan X, Chao RC, Papadopoulos KP. First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1). J Clin Oncol. 2022 Aug 10;40(23):2530-2538. doi: 10.1200/JCO.21.02752. Epub 2022 Feb 15.