Clinical trial NCT05245500: Phase 1 Study of MRTX1719 in Solid Tumors With MTAP Deletion
Official title: A Phase 1 Multiple Expansion Cohort Trial of MRTX1719 in Patients With Advanced Solid Tumors With Homozygous MTAP Deletion
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Mesothelioma
Non Small Cell Lung Cancer
Malignant Peripheral Nerve Sheath Tumors
Solid Tumor
Pancreatic Adenocarcinoma
Advanced Solid Tumor
Keywords: MTAP Deletion
Mesothelioma
Non Small Cell Lung Cancer
Malignant Peripheral Nerve Sheath Tumors
Solid Tumor
MTAP
Malignant
Pancreatic adenocarcinoma
Pancreas Cancer
PRMT5
Synthetic Lethality
Advanced Solid Tumor
NSCLC
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2022-02-18
Enrollment: 320
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, open-label, multicenter, study of the safety, tolerability, PK, PD, and anti-tumor activity of MRTX1719 patients with advanced, unresectable or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene.

Detailed description: This first-in-human clinical trial will begin with an exploration of MRTX1719 dose and regimen. As potentially viable regimens are identified, Phase 1b expansion cohorts may be implemented to ensure sufficient safety experience, PK information, compare food effect and relative bioavailability between capsules and tablets, and early evidence of clinical activity are available.

Eligibility criteria: Inclusion Criteria

* Histologically confirmed diagnosis of a solid tumor malignancy with homozygous deletion of the MTAP gene detected in tumor tissue.
* Unresectable or metastatic 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.
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate organ function.

Exclusion Criteria

* Prior treatment with a PRMT5 or MAT2A inhibitor therapy.
* Active brain metastases or carcinomatous meningitis.
* 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 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.
* Cardiac abnormalities.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Number of Patients who Experience Dose-Limiting Toxicity
timeFrame: 21 days
measure: Number of patients who experience a treatment-related adverse event
timeFrame: Up to 2 years
measure: Objective response rate (ORR)
timeFrame: 2 years
measure: Duration of response (DOR)
timeFrame: 2 years
measure: Progression free survival (PFS)
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
Secondary outcomes:
measure: Area under the 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: Mayo Clinic
state: Arizona
city: Denver
country: United States
facility: Sarah Cannon Research Institute (SCRI) - HealthONE Location
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers, LLP - Oncology
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Orlando
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: Local Institution - 124
state: Illinois
city: Brookline
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Norton Shores
country: United States
facility: Cancer and Hematology Centers of Western Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: David H Koch, Memorial Sloan Kettering Cancer Center
state: New York
city: Port Jefferson Station
country: United States
facility: New york cancer and blood specialists - Oncology
state: New York
city: Chapel Hill
country: United States
facility: Local Institution - 125
state: North Carolina
city: Nashville
country: United States
facility: SCRI
state: Tennessee
city: Nashville
country: United States
facility: Local Institution - 132
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 120
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - DFW
state: Texas
city: Houston
country: United States
facility: MDACC
state: Texas
city: Houston
country: United States
facility: Oncology Consultants - Clinical Research
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. - Oncology
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Local Institution - 134
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - Froedtert Hospital
state: Wisconsin
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: