Advanced Cancer, Metastatic Cancer, Malignant Neoplastic Disease
Conditions
Keywords
KRAS G12C, Non-small cell lung cancer, Colorectal Cancer, Colon Cancer, Metastatic Cancer, Pancreatic Cancer, NSCLC, SHP2, Advanced Solid Tumors
Brief summary
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. This study was terminated prior to phase 2 initiating. Only phase 1 of the study was conducted.
Sponsors
Novartis
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 (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the safety of MRTX849 and TNO155 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 and TNO155 | 20 months | Blood plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Establish maximum tolerated dose | 12 months | Number of participants with dose limiting toxicity |
| Evaluate clinical activity of MRTX849 | 20 months | Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) |
Countries
United States
Outcome results
None listed