UK Center for Clinical and Translational Science

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

Purpose

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

Advanced Cancer
Metastatic Cancer
Malignant Neoplastic Disease

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

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

Study Design

Phase: Phase 1/Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Phase 1 Dose Exploration	Dose escalation of MRTX849 to determine maximum tolerated dose	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental Phase 1b Expansion	Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental Phase 2	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	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental Pilot Phase 1b Combination with Pembrolizumab	Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Pembrolizumab Pembrolizumab is administered as an intravenous infusion once every 3 weeks
Experimental Pilot Phase 1b Combination with Cetuximab	Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Cetuximab Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental Pilot Phase 1b Combination with Afatinib	Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Afatinib Afatinib will be administered orally once a day in a continuous regimen
Experimental Phase 2 Combination with Cetuximab	Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Cetuximab Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental Pilot Phase 1b Combination with Cetuximab in NSCLC	Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Cetuximab Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental Pilot Phase 1b Combination with Cetuximab in PDAC	Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Cetuximab Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky
Lexington, Kentucky 40536

Contact:
Susanne Arnold, Site 001-844
85925744888592573379

More Details

NCT ID: NCT03785249
Status: Recruiting
Sponsor: Mirati Therapeutics Inc.

Study Contact

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
855-907-3286
Clinical.Trials@bms.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.