Clinical trial NCT05737706: Study of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation
Official title: A Phase 1/2 Multiple Expansion Cohort Trial of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor
Advanced Solid Tumor
Non-small Cell Lung Cancer
Colo-rectal Cancer
Pancreatic Adenocarcinoma
Keywords: Non-Small Cell Lung Cancer
NSCLC
colorectal cancer
CRC
PDAC
KRAS
G12D
Solid Tumor
Advanced Solid Tumor
Malignant
Pancreatic Cancer
Pancreatic Adenocarcinoma
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-21
Enrollment: 63
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: A Phase 1/2 study of MRTX1133 in solid tumors harboring a KRAS G12D mutation.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1: Number of Patients who Experience Dose-Limiting Toxicity
timeFrame: 21 Days
measure: Phase 1/1b: 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 plasma concentration versus time curve (AUC)
timeFrame: up to 4 days
measure: Time to achieve maximal plasma concentration (Tmax)
timeFrame: up to 4 days
measure: Maximum observed plasma concentration (Cmax)
timeFrame: up to 4 days
measure: Terminal elimination half-life (t1/2)
timeFrame: up to 4 days
measure: Apparent total plasma clearance when dosed orally (CL/F)
timeFrame: up to 4 days
measure: Apparent volume of distribution when dosed orally (Vz/F)
timeFrame: up to 4 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Local Institution - 311
state: Arizona
city: New Haven
country: United States
facility: Local Institution - 309
state: Connecticut
city: Lady Lake
country: United States
facility: Local Institution - 301
state: Florida
city: Baltimore
country: United States
facility: Local Institution - 306
state: Maryland
city: Boston
country: United States
facility: Local Institution - 308
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 310
state: Massachusetts
city: Grand Rapids
country: United States
facility: Local Institution - 314
state: Michigan
city: New York
country: United States
facility: Local Institution - 312
state: New York
city: Nashville
country: United States
facility: Local Institution - 303
state: Tennessee
city: Houston
country: United States
facility: Local Institution - 302
state: Texas
city: San Antonio
country: United States
facility: Local Institution - 304
state: Texas
city: San Antonio
country: United States
facility: Local Institution - 313
state: Texas
city: Fairfax
country: United States
facility: Local Institution - 305
state: Virginia
city: Seattle
country: United States
facility: Local Institution - 307
state: Washington
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: