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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05737706
• Other study ID #: 1133-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 20, 2023
• Est. completion date: August 30, 2026

Study information

• Verified date: November 2023
• Source: Mirati Therapeutics Inc.
• Contact: Mirati Therapeutics Study Locator Services
• Phone: 18448935530
• Email: miratistudylocator[@]careboxhealth.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 386
• Est. completion date: August 30, 2026
• Est. primary completion date: August 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Solid Tumor
• Carcinoma, Non-Small-Cell Lung
• Colo-rectal Cancer
• Neoplasms
• Non-small Cell Lung Cancer
• Pancreatic Adenocarcinoma
• Solid Tumor

Intervention

Drug:
• MRTX1133
KRAS G12D Inhibitor

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	NEXT Oncology Virginia	Fairfax	Virginia
United States	START Midwest	Grand Rapids	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	SCRI - TN Oncology Nashville Drug Development Unit Clinic	Nashville	Tennessee
United States	Yale University, Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Sarah Cannon Research Institute at Florida Cancer Specialists	Orlando	Florida
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	NEXT Oncology	San Antonio	Texas
United States	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	Fred Hutchinson Cancer Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Number of Patients who Experience Dose-Limiting Toxicity		21 Days
Primary	Phase 1/1b: Number of patients who experience a treatment-related adverse event		Up to 2 years
Primary	Phase 2: Objective response rate (ORR)		2 years
Primary	Phase 2: Duration of response (DOR)		2 years
Primary	Phase 2: Progression free survival (PFS)		2 years
Primary	Phase 2: Overall survival (OS)		2 years
Secondary	Area under plasma concentration versus time curve (AUC)		up to 4 days
Secondary	Time to achieve maximal plasma concentration (Tmax)		up to 4 days
Secondary	Maximum observed plasma concentration (Cmax)		up to 4 days
Secondary	Terminal elimination half-life (t1/2)		up to 4 days
Secondary	Apparent total plasma clearance when dosed orally (CL/F)		up to 4 days
Secondary	Apparent volume of distribution when dosed orally (Vz/F)		up to 4 days