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

Sponsor

Mirati Therapeutics Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05737706

Collaborator

(none)

304

Enrollment

Arms

42.2

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a Phase 1/2, open-label, multicenter, study evaluating the safety, tolerability, PK, PD, and anti-tumor activity of MRTX1133 in patients with advanced solid tumor malignancy harboring a KRAS G12D mutation.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Advanced Solid Tumor Non-small Cell Lung Cancer Colo-rectal Cancer Pancreatic Adenocarcinoma	Drug: MRTX1133	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

304 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Feb 23, 2023

Anticipated Primary Completion Date :

Aug 30, 2026

Anticipated Study Completion Date :

Aug 30, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.