Description:
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.
Title
- Brief Title: Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1
- Official Title: A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1
Clinical Trial IDs
- ORG STUDY ID:
849-001
- NCT ID:
NCT03785249
Conditions
- Advanced Cancer
- Metastatic Cancer
- Malignant Neoplastic Disease
Interventions
Drug | Synonyms | Arms |
---|
MRTX849 | | Phase 1 Dose Exploration |
Pembrolizumab | | Pilot Phase 1b Combination with Pembrolizumab |
Cetuximab | | Pilot Phase 1b Combination with Cetuximab |
Afatinib | | Pilot Phase 1b Combination with Afatinib |
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1 Dose Exploration | Experimental | Dose escalation of MRTX849 to determine maximum tolerated dose | |
Phase 1b Expansion | Experimental | Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens | |
Phase 2 | Experimental | Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity of MRTX849 | |
Pilot Phase 1b Combination with Pembrolizumab | Experimental | Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC | |
Pilot Phase 1b Combination with Cetuximab | Experimental | Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC | |
Pilot Phase 1b Combination with Afatinib | Experimental | Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC | |
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
- Adequate organ function
Exclusion Criteria:
- History of intestinal disease or major gastric surgery or inability to swallow oral
medications
- Other active cancer
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation |
Time Frame: | 20 months |
Safety Issue: | |
Description: | Number of participants with treatment related adverse events |
Secondary Outcome Measures
Measure: | Establish maximum tolerated dose |
Time Frame: | 12 months |
Safety Issue: | |
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 |
Safety Issue: | |
Description: | Number of participants with dose limiting toxicity |
Measure: | Evaluate the pharmacokinetics of new MRTX849 oral formulations |
Time Frame: | 6 months |
Safety Issue: | |
Description: | Blood plasma concentration |
Measure: | Evaluate the pharmacokinetics of MRTX849 administered with food |
Time Frame: | 6 months |
Safety Issue: | |
Description: | Blood plasma concentration |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Mirati Therapeutics Inc. |
Trial Keywords
- KRAS
- NSCLC
- Colorectal Cancer
- Colon Cancer
- Metastatic Cancer
- Pancreatic Cancer
- Adagrasib
Last Updated
July 14, 2021