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

Phase 1

Terminated

• Conditions: Advanced Solid Tumor; Colo-rectal Cancer; Non-small Cell Lung Cancer; Solid Tumor; Pancreatic Adenocarcinoma
• Interventions: Drug: MRTX1133

• Registration Number: NCT05737706
• Lead Sponsor: Mirati Therapeutics Inc.

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.

Study Timeline

• Study First Submitted: 2023-02-10
• Study First Submitted QC: 2023-02-10
• Study First Posted: 2023-02-21
• Study Start: 2023-03-06
• Primary Completion: 2025-03-10
• Study Completion: 2025-03-10
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-03
• Last Update Posted: 2025-04-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 63

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1/1B	MRTX1133	Dose Escalation/Evaluation
Phase 2	MRTX1133	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

Primary Outcome Measures

Name	Time	Method
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: Progression free survival (PFS)	2 years
Phase 1: Number of Patients who Experience Dose-Limiting Toxicity	21 Days
Phase 2: Duration of response (DOR)	2 years
Phase 2: Overall survival (OS)	2 years

Secondary Outcome Measures

Name	Time	Method
Apparent total plasma clearance when dosed orally (CL/F)	up to 4 days
Area under plasma concentration versus time curve (AUC)	up to 4 days
Terminal elimination half-life (t1/2)	up to 4 days
Apparent volume of distribution when dosed orally (Vz/F)	up to 4 days
Maximum observed plasma concentration (Cmax)	up to 4 days
Time to achieve maximal plasma concentration (Tmax)	up to 4 days

Trial Locations

Locations (14)

Local Institution - 311; 🇺🇸 Phoenix, Arizona, United States

Local Institution - 309; 🇺🇸 New Haven, Connecticut, United States

Local Institution - 301; 🇺🇸 Lady Lake, Florida, United States

Local Institution - 306; 🇺🇸 Baltimore, Maryland, United States

Local Institution - 308; 🇺🇸 Boston, Massachusetts, United States

Local Institution - 310; 🇺🇸 Boston, Massachusetts, United States

Local Institution - 314; 🇺🇸 Grand Rapids, Michigan, United States

Local Institution - 312; 🇺🇸 New York, New York, United States

Local Institution - 303; 🇺🇸 Nashville, Tennessee, United States

Local Institution - 302; 🇺🇸 Houston, Texas, United States

Local Institution - 304; 🇺🇸 San Antonio, Texas, United States

Local Institution - 313; 🇺🇸 San Antonio, Texas, United States

Local Institution - 305; 🇺🇸 Fairfax, Virginia, United States

Local Institution - 307; 🇺🇸 Seattle, Washington, United States