A Phase 1/2 Study of MRTX0902 in Solid Tumors With Mutations in the KRAS MAPK Pathway

Sponsor

Mirati Therapeutics Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05578092

Collaborator

(none)

225

Enrollment

Locations

Arms

44.8

Anticipated Duration (Months)

Patients Per Site

1.7

Patients Per Site Per Month

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 MRTX0902 alone and in combination with MRTX849 (adagrasib) in patients with advanced solid tumor malignancy harboring mutations in the KRAS, MAPK pathways.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Advanced Solid Tumor Non Small Cell Lung Cancer Colo-rectal Cancer	Drug: MRTX0902 Drug: MRTX849	Phase 1/Phase 2

Detailed Description

This first-in-human clinical trial will begin with an exploration of MRTX0902 dose and regimen. Once safety experience and PK data are available for the monotherapy regimen, dose escalation of the combination of MRTX0902 and adagrasib will be initiated. 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 MRTX0902 in combination with adagrasib.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

225 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 the SOS1 Inhibitor MRTX0902 in Patients With Advanced Solid Tumors Harboring Mutations in the KRAS MAPK Pathway

Actual Study Start Date :

Nov 4, 2022

Anticipated Primary Completion Date :

Jun 30, 2026

Anticipated Study Completion Date :

Jul 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1/1B Monotherapy Dose Escalation/Evaluation	Drug: MRTX0902 SOS1 inhibitor
Experimental: Phase 1/1B Combination Therapy Dose Escalation/Evaluation	Drug: MRTX0902 SOS1 inhibitor Drug: MRTX849 KRAS G12C inhibitor Other Names: adagrasib
Experimental: Phase 2 MRTX0902 and adagrasib combination RP2D administered to separate cohorts of patients with selected solid tumor malignancies with KRAS G12C mutation to include the following: NSCLC, CRC, Other Solid Tumors	Drug: MRTX0902 SOS1 inhibitor Drug: MRTX849 KRAS G12C inhibitor Other Names: adagrasib

Arm

Intervention/Treatment

Experimental: Phase 1/1B Monotherapy

Dose Escalation/Evaluation

Drug: MRTX0902

SOS1 inhibitor

Experimental: Phase 1/1B Combination Therapy

Dose Escalation/Evaluation

Drug: MRTX0902

SOS1 inhibitor

Drug: MRTX849

KRAS G12C inhibitor

Other Names:

adagrasib

Experimental: Phase 2

MRTX0902 and adagrasib combination RP2D administered to separate cohorts of patients with selected solid tumor malignancies with KRAS G12C mutation to include the following: NSCLC, CRC, Other Solid Tumors

Drug: MRTX0902

SOS1 inhibitor

Drug: MRTX849

KRAS G12C inhibitor

Other Names:

adagrasib

Outcome Measures

Primary Outcome Measures

Phase 1: Number of Patients who Experience Dose-Limiting Toxicity [21 Days]
Phase1/1B: 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 the plasma concentration versus time curve [Up to 4 days]
AUC - MRTX0902 and adagrasib
Time to achieve maximal plasma concentration [Up to 4 days]
Tmax - MRTX0902 and adagrasib
Maximum observed plasma concentration [Up to 4 days]
Cmax - MRTX0902 and adagrasib
Terminal elimination half-life [Up to 4 days]
t1/2 - MRTX0902
Apparent total plasma clearance when dosed orally [Up to 4 days]
CL/F - MRTX0902
Apparent volume of distribution when dosed orally [Up to 4 days]
Vz/F - MRTX0902

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 with any of the following oncogenic mutations detected in tumor tissue or ctDNA by a sponsor-approved test:

MRTX0902 monotherapy: known KRAS mutations, known annotated recurrent activating SOS1, PTPN11, or EGFR mutation, or known annotated recurrent inactivating NF1 mutation;
MRTX0902 and adagrasib combination therapy: KRAS G12C mutation.

Unresectable or metastatic disease
No available treatment with curative intent; standard treatment is not available or patient declines
Presence of tumor lesions to be evaluated per RECIST 1.1:

Phase 1 dose escalation, RECIST 1.1 measurable or evaluable disease
Phase 1b and Phase 2 cohorts, RECIST 1.1 measurable disease

Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic evaluation at baseline and on-study unless Sponsor-confirmed as medically unsafe or infeasible.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Adequate organ function

Exclusion Criteria:

Active brain metastases or carcinomatous meningitis
Prior treatment with a KRAS G12C inhibitor (for Phase 1b expansion for MRTX0902 and adagrasib combination, and Phase 2 cohorts only)
History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of study treatment.
Major surgery within 4 weeks of first dose of study treatment
History of pneumonitis or interstitial lung disease
Ongoing need for medication with following characteristics: substrate of CYP3A; strong inducer or inhibitor or CYP3A and/or P-gp; strong inhibitors of BRCP and proton pump inhibitors
Cardiac abnormalities
History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Denver Drug Development Unit - HealthONE	Denver	Colorado	United States	80218
2	SCRI - TN Oncology Nashville Drug Development Unit Clinic	Nashville	Tennessee	United States	37203
3	NEXT Oncology Virginia	Fairfax	Virginia	United States	22031