Advanced Solid Tumor, Colo-rectal Cancer, Non-small Cell Lung Cancer, Pancreatic Adenocarcinoma, Solid Tumor
Conditions
Keywords
Non-Small Cell Lung Cancer, NSCLC, colorectal cancer, CRC, PDAC, KRAS, G12D, Solid Tumor, Advanced Solid Tumor, Malignant, Pancreatic Cancer, Pancreatic Adenocarcinoma
Brief summary
A Phase 1/2 study of MRTX1133 in solid tumors harboring a KRAS G12D mutation.
Detailed description
This first-in-human clinical trial will begin with an exploration of MRTX1133 dose and regimen. As potentially viable regimens are identified, Phase 1b expansion cohorts may be implemented to ensure collection of sufficient safety and PK information, and early evidence of clinical activity are available to recommend Phase 2 regimens. In Phase 2, separate cohorts of patients by histological diagnosis and/or baseline characteristics will be evaluated for the clinical activity and efficacy of MRTX1133. This study was terminated prior to phase 2 initiating. Only phase 1 of the study was conducted.
Interventions
DRUGMRTX1133
KRAS G12D Inhibitor
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 harboring KRAS G12D mutation in tumor tissue or ctDNA. * Unresectable or metastatic disease. * Patients must have received standard therapies appropriate for their tumor type and stage; first-line treatment for PDAC for certain cohorts. * Presence of tumor lesions to be evaluated per RECIST v1.1: 1. in the Phase 1 dose escalation cohorts, patients must have measurable or evaluable disease. 2. in the Phase 1b and Phase 2 cohorts, patients must have measurable disease. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate organ function. * Age ≥ 18 years
Exclusion criteria
* Active brain metastases or carcinomatous meningitis. * Prior treatment with a KRAS G12D inhibitor (Phase 1b & Phase 2 only). * History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of study treatment. * 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 oral medications. * History of malignant small bowel obstruction. * Cardiac abnormalities.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 2: Overall survival (OS) | 2 years |
| Phase 1: Number of Patients who Experience Dose-Limiting Toxicity | 21 Days |
| Phase 1/1b: Number of patients who experience a treatment-related adverse event | Up to 2 years |
| Phase 2: Objective response rate (ORR) | 2 years |
| Phase 2: Duration of response (DOR) | 2 years |
| Phase 2: Progression free survival (PFS) | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Area under plasma concentration versus time curve (AUC) | up to 4 days |
| Time to achieve maximal plasma concentration (Tmax) | up to 4 days |
| Maximum observed plasma concentration (Cmax) | up to 4 days |
| Terminal elimination half-life (t1/2) | up to 4 days |
| Apparent total plasma clearance when dosed orally (CL/F) | up to 4 days |
| Apparent volume of distribution when dosed orally (Vz/F) | up to 4 days |
Countries
United States
Outcome results
None listed