A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Mirati Therapeutics Inc.
- Enrollment
- 731
- Locations
- 444
- Primary Endpoint
- Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- 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
Arms & Interventions
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
Intervention: Pembrolizumab (Drug)
Phase 2 Combination with Cetuximab
Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC
Intervention: MRTX849 (Drug)
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
Intervention: Cetuximab (Drug)
Phase 2 Combination with Cetuximab
Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC
Intervention: Cetuximab (Drug)
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)
Intervention: MRTX849 (Drug)
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
Intervention: Cetuximab (Drug)
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
Intervention: MRTX849 (Drug)
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
Intervention: MRTX849 (Drug)
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
Intervention: MRTX849 (Drug)
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
Intervention: MRTX849 (Drug)
Phase 1 Dose Exploration
Dose escalation of MRTX849 to determine maximum tolerated dose
Intervention: MRTX849 (Drug)
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
Intervention: MRTX849 (Drug)
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
Intervention: MRTX849 (Drug)
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
Intervention: Afatinib (Drug)
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)
Intervention: Cetuximab (Drug)
Outcomes
Primary Outcomes
Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation
Time Frame: 20 months
Number of participants with treatment related adverse events
Evaluate the pharmacokinetics of MRTX849
Time Frame: 20 months
Blood plasma concentration
Evaluate clinical activity/efficacy of MRTX849
Time Frame: 20 months
Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
Secondary Outcomes
- Establish maximum tolerated dose(12 months)
- Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents(12 months)
- Evaluate the pharmacokinetics of new MRTX849 oral formulations(6 months)
- Evaluate the pharmacokinetics of MRTX849 administered with food(6 months)