Clinical trial NCT05578092: A Phase 1/2 Study of MRTX0902 in Solid Tumors With Mutations in the KRAS MAPK Pathway
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Advanced Solid Tumor
Non Small Cell Lung Cancer
Colo-rectal Cancer
Keywords: Non Small Cell Lung Cancer
NSCLC
Colorectal Cancer
CRC
EGFR
KRAS
SOS1
Solid Tumor
Advanced Solid Tumor
Malignant
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-13
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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, and will include a separate preliminary food effect assessments on MRTX0902 PK in combination with adagrasib. 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.

Eligibility criteria: 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:

  1. MRTX0902 monotherapy: known KRAS mutations, known annotated recurrent activating SOS1, PTPN11, class III BRAF, or EGFR mutation, or known annotated recurrent inactivating NF1 mutation;
  2. 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:

  1. Phase 1 dose escalation, RECIST 1.1 measurable or evaluable disease
  2. 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

Primary outcomes:
measure: Phase 1: Number of Patients who Experience Dose-Limiting Toxicity
timeFrame: 21 Days
measure: Phase1/1B: Number of patients who experience a treatment-related adverse event
timeFrame: Up to 2 years
measure: Phase 2: Objective response rate (ORR)
timeFrame: 2 years
measure: Phase 2: Duration of response (DOR)
timeFrame: 2 years
measure: Phase 2: Progression free survival (PFS)
timeFrame: 2 years
measure: Phase 2: Overall survival (OS)
timeFrame: 2 years
Secondary outcomes:
measure: Area under the plasma concentration versus time curve
timeFrame: Up to 4 days
measure: Time to achieve maximal plasma concentration
timeFrame: Up to 4 days
measure: Maximum observed plasma concentration
timeFrame: Up to 4 days
measure: Terminal elimination half-life
timeFrame: Up to 4 days
measure: Apparent total plasma clearance when dosed orally
timeFrame: Up to 4 days
measure: Apparent volume of distribution when dosed orally
timeFrame: Up to 4 days
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: Local Institution - 001-120
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants
state: Delaware
city: Washington
country: United States
facility: Local Institution - 001-113
state: District of Columbia
city: Orlando
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Specialists
state: Florida
city: Baltimore
country: United States
facility: Local Institution - 001-118
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Minneapolis
country: United States
facility: Local Institution - 001-125
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Cancer Center - Rochester - PPDS
state: Minnesota
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: Bronx
country: United States
facility: Local Institution - 001-117
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Portland
country: United States
facility: Local Institution - 001-109
state: Oregon
city: Pittsburgh
country: United States
facility: Local Institution - 001-116
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Central Office
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology NASH
state: Tennessee
city: Austin
country: United States
facility: Local Institution - 001-121
state: Texas
city: Dallas
country: United States
facility: (USOR) Texas Oncology
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Tyler
country: United States
facility: University of Texas Health Science Center at Tyler
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: