Solid Tumor, Advanced Solid Tumor, Non Small Cell Lung Cancer, Colo-rectal Cancer
Conditions
Keywords
Non Small Cell Lung Cancer, NSCLC, Colorectal Cancer, CRC, EGFR, KRAS, SOS1, Solid Tumor, Advanced Solid Tumor, Malignant
Brief summary
This is a Phase 1, open-label, multicenter, study evaluating the safety, tolerability, PK, PD, and anti-tumor activity of MRTX0902 alone and in combination with MRTX849 (adagrasib) in patients with advanced solid tumor malignancy harboring mutations in the KRAS-MAPK pathways.
Detailed description
This first-in-human clinical trial will begin with an exploration of MRTX0902 dose and regimen. Once safety experience and PK data are available for the monotherapy regimen, dose escalation of the combination of MRTX0902 and adagrasib will be initiated, and will include a separate preliminary food effect assessments on MRTX0902 PK in combination with adagrasib. As potentially viable regimens are identified, Phase 1b expansion cohorts may be implemented to ensure collection of sufficient safety and PK information.
Interventions
DRUGMRTX0902
SOS1 inhibitor
DRUGMRTX849
KRAS G12C 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 with any of the following oncogenic mutations detected in tumor tissue or ctDNA by a sponsor-approved test: 1. MRTX0902 monotherapy: known KRAS mutations, known annotated recurrent activating SOS1, PTPN11, class III BRAF, or EGFR mutation, or known annotated recurrent inactivating NF1 mutation; 2. MRTX0902 and adagrasib combination therapy: KRAS G12C mutation. * Unresectable or metastatic disease * No available treatment with curative intent; standard treatment is not available or patient declines * Presence of tumor lesions to be evaluated per RECIST 1.1. Phase 1 dose escalation, RECIST 1.1 measurable or evaluable disease * Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic evaluation at baseline and on-study unless Sponsor-confirmed as medically unsafe or infeasible. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate organ function
Exclusion criteria
* Active brain metastases or carcinomatous meningitis * Prior treatment with a KRAS G12C inhibitor (for Phase 1b expansion for MRTX0902 and adagrasib combination). * History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of study treatment. * Major surgery within 4 weeks of first dose of study treatment * History of pneumonitis or interstitial lung disease * Ongoing need for medication with following characteristics: substrate of CYP3A; strong inducer or inhibitor or CYP3A and/or P-gp; strong inhibitors of BRCP and proton pump inhibitors * Cardiac abnormalities * History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Patients who Experience Dose-Limiting Toxicity | 21 Days |
| Number of patients who experience a treatment-related adverse event | Up to 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration versus time curve | Up to 4 days | AUC - MRTX0902 and adagrasib |
| Time to achieve maximal plasma concentration | Up to 4 days | Tmax - MRTX0902 and adagrasib |
| Maximum observed plasma concentration | Up to 4 days | Cmax - MRTX0902 and adagrasib |
| Terminal elimination half-life | Up to 4 days | t1/2 - MRTX0902 |
| Apparent total plasma clearance when dosed orally | Up to 4 days | CL/F - MRTX0902 |
| Apparent volume of distribution when dosed orally | Up to 4 days | Vz/F - MRTX0902 |
Countries
Puerto Rico, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed