NCT03785249 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE1, PHASE2
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-07-29

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Dose escalation of MRTX849 to determine maximum tolerated dose
intervention Names
Drug: MRTX849
label
Phase 1 Dose Exploration
type
EXPERIMENTAL
description
Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens
intervention Names
Drug: MRTX849
label
Phase 1b Expansion
type
EXPERIMENTAL
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
intervention Names
Drug: MRTX849
label
Phase 2
type
EXPERIMENTAL
description
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC
intervention Names
Drug: MRTX849
Drug: Pembrolizumab
label
Pilot Phase 1b Combination with Pembrolizumab
type
EXPERIMENTAL
description
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC
intervention Names
Drug: MRTX849
Drug: Cetuximab
label
Pilot Phase 1b Combination with Cetuximab
type
EXPERIMENTAL
description
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC
intervention Names
Drug: MRTX849
Drug: Afatinib
label
Pilot Phase 1b Combination with Afatinib
type
EXPERIMENTAL
description
Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC
intervention Names
Drug: MRTX849
Drug: Cetuximab
label
Phase 2 Combination with Cetuximab
type
EXPERIMENTAL
description
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC
intervention Names
Drug: MRTX849
Drug: Cetuximab
label
Pilot Phase 1b Combination with Cetuximab in NSCLC
type
EXPERIMENTAL
description
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)
intervention Names
Drug: MRTX849
Drug: Cetuximab
label
Pilot Phase 1b Combination with Cetuximab in PDAC
type
EXPERIMENTAL

interventions

arm Group Labels
Phase 1 Dose Exploration
Phase 1b Expansion
Phase 2
Phase 2 Combination with Cetuximab
Pilot Phase 1b Combination with Afatinib
Pilot Phase 1b Combination with Cetuximab
Pilot Phase 1b Combination with Cetuximab in NSCLC
Pilot Phase 1b Combination with Cetuximab in PDAC
Pilot Phase 1b Combination with Pembrolizumab
description
MRTX849 will be administered orally once or twice daily in a continuous regimen
name
MRTX849
type
DRUG
arm Group Labels
Pilot Phase 1b Combination with Pembrolizumab
description
Pembrolizumab is administered as an intravenous infusion once every 3 weeks
name
Pembrolizumab
type
DRUG
arm Group Labels
Phase 2 Combination with Cetuximab
Pilot Phase 1b Combination with Cetuximab
Pilot Phase 1b Combination with Cetuximab in NSCLC
Pilot Phase 1b Combination with Cetuximab in PDAC
description
Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
name
Cetuximab
type
DRUG
arm Group Labels
Pilot Phase 1b Combination with Afatinib
description
Afatinib will be administered orally once a day in a continuous regimen
name
Afatinib
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 731
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Number of participants with treatment related adverse events
measure
Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation
time Frame
20 months
description
Blood plasma concentration
measure
Evaluate the pharmacokinetics of MRTX849
time Frame
20 months
description
Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
measure
Evaluate clinical activity/efficacy of MRTX849
time Frame
20 months

secondary Outcomes

description
Number of participants with dose limiting toxicity
measure
Establish maximum tolerated dose
time Frame
12 months
description
Number of participants with dose limiting toxicity
measure
Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents
time Frame
12 months
description
Blood plasma concentration
measure
Evaluate the pharmacokinetics of new MRTX849 oral formulations
time Frame
6 months
description
Blood plasma concentration
measure
Evaluate the pharmacokinetics of MRTX849 administered with food
time Frame
6 months

Full study description

brief Summary: 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.
detailed Description: This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.

Source references

references

citation
Negrao 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
type
DERIVED
citation
Bekaii-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
type
DERIVED
citation
Yaeger 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
type
DERIVED
citation
Janne 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
type
DERIVED
citation
Sabari 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
type
DERIVED
citation
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.
pmid
35167329
type
DERIVED
citation
Awad MM, Liu S, Rybkin II, Arbour KC, Dilly J, Zhu VW, Johnson ML, Heist RS, Patil T, Riely GJ, Jacobson JO, Yang X, Persky NS, Root DE, Lowder KE, Feng H, Zhang SS, Haigis KM, Hung YP, Sholl LM, Wolpin BM, Wiese J, Christiansen J, Lee J, Schrock AB, Lim LP, Garg K, Li M, Engstrom LD, Waters L, Lawson JD, Olson P, Lito P, Ou SI, Christensen JG, Janne PA, Aguirre AJ. Acquired Resistance to KRASG12C Inhibition in Cancer. N Engl J Med. 2021 Jun 24;384(25):2382-2393. doi: 10.1056/NEJMoa2105281.
pmid
34161704
type
DERIVED