Advanced Cancer, Metastatic Cancer, Malignant Neoplastic Disease
Conditions
Keywords
KRAS, NSCLC, Colorectal Cancer, Colon Cancer, Metastatic Cancer, Pancreatic Cancer, Adagrasib, STK11 mutation, KRAS G12C
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.
Interventions
DRUGMRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen
DRUGPembrolizumab
Pembrolizumab is administered as an intravenous infusion once every 3 weeks
DRUGCetuximab
Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
DRUGAfatinib
Afatinib will be administered orally once a day in a continuous regimen
Sponsors
Mirati Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation | 20 months | Number of participants with treatment related adverse events |
| Evaluate the pharmacokinetics of MRTX849 | 20 months | Blood plasma concentration |
| Evaluate clinical activity/efficacy of MRTX849 | 20 months | Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Establish maximum tolerated dose | 12 months | Number of participants with dose limiting toxicity |
| Evaluate the pharmacokinetics of MRTX849 administered with food | 6 months | Blood plasma concentration |
| Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents | 12 months | Number of participants with dose limiting toxicity |
| Evaluate the pharmacokinetics of new MRTX849 oral formulations | 6 months | Blood plasma concentration |
Countries
Puerto Rico, United States
Outcome results
None listed