Study of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation

Study Overview
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Brief Summary
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A Phase 1/2 study of MRTX1133 in solid tumors harboring a KRAS G12D mutation.

Detailed Description
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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.

Official Title
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A Phase 1/2 Multiple Expansion Cohort Trial of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation

Conditions
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Solid Tumor, Advanced Solid Tumor, Non-small Cell Lung Cancer, Colo-rectal Cancer, Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: MRTX1133


Participation Criteria
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Eligibility Criteria
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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: in the Phase 1 dose escalation cohorts, patients must have measurable or evaluable disease. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1/1B<br>Dose Escalation/Evaluation | Drug: MRTX1133<br>* KRAS G12D Inhibitor<br>|
| Experimental: Phase 2<br>MRTX1133 recommended Phase 2 dose administered to separate cohorts of patients with selected solid tumor malignancies with KRAS G12D mutation to include the following: NSCLC, PDAC, CRC, Other Solid Tumors | Drug: MRTX1133<br>* KRAS G12D Inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Phase 2: Overall survival (OS) |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, NSCLC, colorectal cancer, CRC, PDAC, KRAS, G12D, Solid Tumor, Advanced Solid Tumor, Malignant, Pancreatic Cancer, Pancreatic Adenocarcinoma