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.