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

A Phase 1/2 Multiple Expansion Cohort Trial 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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Adenocarcinoma; Solid Tumor; Advanced Solid Tumor; Non-small Cell Lung Cancer; Colo-rectal Cancer
• Intervention / Treatment: Drug: MRTX1133

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 Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Local Institution - 311
  • Connecticut
    • New Haven, Connecticut, United States, 06520 8028
      • Local Institution - 309
  • Florida
    • Lady Lake, Florida, United States, 32159 8987
      • Local Institution - 301
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Local Institution - 306
  • Massachusetts
    • Boston, Massachusetts, United States, 02114 3117
      • Local Institution - 308
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 310
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Local Institution - 314
  • New York
    • New York, New York, United States, 10065 6800
      • Local Institution - 312
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 303
  • Texas
    • Houston, Texas, United States, 77030
      • Local Institution - 302
    • San Antonio, Texas, United States, 78229 3307
      • Local Institution - 304
    • San Antonio, Texas, United States, 78229
      • Local Institution - 313
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Local Institution - 305
  • Washington
    • Seattle, Washington, United States, 98109 1023
      • Local Institution - 307

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 1: Number of Patients who Experience Dose-Limiting Toxicity	21 Days
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
Phase 1/1b: Number of patients who experience a treatment-related adverse event	Up to 2 years

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2023
• Primary Completion (Actual): March 10, 2025
• Study Completion (Actual): March 10, 2025

Study Registration Dates

• First Submitted: February 10, 2023
• First Submitted That Met QC Criteria: February 10, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: colorectal cancer; NSCLC; Non-Small Cell Lung Cancer; Pancreatic Cancer; Malignant; Solid Tumor; Advanced Solid Tumor; KRAS; CRC; Pancreatic Adenocarcinoma; PDAC; G12D
• Additional Relevant MeSH Terms: Neoplasms by Site; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma
• Other Study ID Numbers: CA246-0005 (Other Identifier: Bristol-Myers Squibb Protocol ID); 1133-001 (Other Identifier: Mirati Therapeutics Protocol ID)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No