Description:
This study will evaluate the safety, tolerability, drug levels, molecular effects, and
clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid
tumors that have a KRAS G12C mutation.
Title
- Brief Title: Phase 1/2 Study in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL 2
- Official Title: A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2
Clinical Trial IDs
- ORG STUDY ID:
849-002
- NCT ID:
NCT04330664
Conditions
- Advanced Cancer
- Metastatic Cancer
- Malignant Neoplastic Disease
Interventions
| Drug | Synonyms | Arms |
|---|
| MRTX849 | | Phase 1 Dose Exploration |
| TNO155 | | Phase 1 Dose Exploration |
Purpose
This study will evaluate the safety, tolerability, drug levels, molecular effects, and
clinical activity of MRTX849 in combination with TNO155 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 in combination with TNO155 in patients
with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small
molecule inhibitor of KRAS G12C and TNO155 is a selective, orally bioavailable allosteric
inhibitor of wild-type SHP2.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Phase 1 Dose Exploration | Experimental | Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849 | |
| Phase 1b Expansion | Experimental | Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with TNO155 to recommend Phase 2 regimens | |
| Phase 2 | Experimental | Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination | |
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation
(phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer)
- Unresectable or metastatic disease
- No available treatment with curative intent
- Adequate organ function
Exclusion Criteria:
- History of intestinal disease, inflammatory bowel disease, major gastric surgery, or
other gastrointestinal conditions likely to alter absorption of study treatment or
result in inability to swallow
- Other active cancer
- Cardiac abnormalities
| 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 and TNO155 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: | Evaluate clinical activity of MRTX849 |
| Time Frame: | 20 months |
| Safety Issue: | |
| Description: | Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Mirati Therapeutics Inc. |
Trial Keywords
- KRAS G12C
- Non-small cell lung cancer
- Colorectal Cancer
- Colon Cancer
- Metastatic Cancer
- Pancreatic Cancer
- NSCLC
- SHP2
- Advanced Solid Tumors
Last Updated
May 13, 2021
