Study Of MRTX1133 In Patients With Advanced Solid Tumors Harboring A KRAS G12D Mutation

Study Overview

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

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

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.

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

DRUG: MRTX1133

CA246-0005
CA246-0005 (OTHER Identifier) (OTHER: Bristol-Myers Squibb Protocol ID)
1133-001 (OTHER Identifier) (OTHER: Mirati Therapeutics Protocol ID)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2023-02-10	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-03
First Submitted that Met QC Criteria 2023-02-10	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-06
First Posted (ACTUAL) 2023-02-21	Results First Posted N/A	Last Verified 2025-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 1/1B Dose Escalation/Evaluation	DRUG: MRTX1133 KRAS G12D Inhibitor
EXPERIMENTAL: Phase 2 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 KRAS G12D Inhibitor

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Phase 1/1B

Dose Escalation/Evaluation

DRUG: MRTX1133

KRAS G12D Inhibitor

EXPERIMENTAL: Phase 2

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

KRAS G12D Inhibitor

Primary Outcome Measures	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	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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:

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Adequate organ function.
Age ≥ 18 years

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

Patients

Caregivers

Clinical Trial Record