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Phase 1/2 Study of MRTX1719 in Solid Tumors With MTAP Deletion

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05245500
Recruitment Status : Recruiting
First Posted : February 18, 2022
Last Update Posted : August 10, 2022
Sponsor:
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Brief Summary:
This is a Phase 1/2, 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.

Condition or disease Intervention/treatment Phase
Mesothelioma Non Small Cell Lung Cancer Malignant Peripheral Nerve Sheath Tumors Solid Tumor Pancreatic Adenocarcinoma Advanced Solid Tumor Drug: MRTX1719 Phase 1 Phase 2

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, 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 MRTX1719.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 339 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 MRTX1719 in Patients With Advanced Solid Tumors With MTAP Homozygous Deletion
Actual Study Start Date : June 2, 2022
Estimated Primary Completion Date : January 31, 2024
Estimated Study Completion Date : January 31, 2024


Arm Intervention/treatment
Experimental: Phase 1/1B
Dose Escalation/Evaluation
Drug: MRTX1719
MRTX1719 is a potent PRMT5-MTA inhibitor

Experimental: Phase 2
MRTX1719 RP2D administered to separate cohorts of patients with selected solid tumor malignancies with MTAP homozygous deletion to include the following: Mesothelioma, Pancreatic Adenocarcinoma, NSCLC, Malignant Peripheral Nerve Sheath Tumor, Other Solid Tumors
Drug: MRTX1719
MRTX1719 is a potent PRMT5-MTA inhibitor




Primary Outcome Measures :
  1. Phase 1: Number of Patients who Experience Dose-Limiting Toxicity [ Time Frame: 21 days ]
  2. Phase 1/1B: Number of patients who experience a treatment-related adverse event [ Time Frame: Up to 2 years ]
  3. Phase 2: Objective response rate (ORR) [ Time Frame: 2 years ]
  4. Phase 2: Duration of response (DOR) [ Time Frame: 2 years ]
  5. Phase 2: Progression free survival (PFS) [ Time Frame: 2 years ]
  6. Phase 2: Overall survival (OS) [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 4 days ]
  2. Time to achieve maximal plasma concentration (Tmax) [ Time Frame: Up to 4 days ]
  3. Maximum observed plasma concentration (Cmax) [ Time Frame: Up to 4 days ]
  4. Terminal elimination half-life (t1/2) [ Time Frame: Up to 4 days ]
  5. Apparent total plasma clearance when dosed orally (CL/F) [ Time Frame: Up to 4 days ]
  6. Apparent volume of distribution when dosed orally (Vz/F) [ Time Frame: Up to 4 days ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis of a solid tumor malignancy with homozygous deletion of the MTAP gene detected in tumor tissue or ctDNA
  • Unresectable or metastatic disease.
  • Patients must have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment.

    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.
  • 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 (Phase 2 only).
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05245500


Contacts
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Contact: Mirati Therapeutics Study Locator Services 1-844-893-5530 miratistudylocator@emergingmed.com

Locations
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United States, Colorado
Sarah Cannon Research Institute at HealthONE Recruiting
Denver, Colorado, United States, 80218
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
START Center for Cancer Care Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Mirati Therapeutics Inc.
Investigators
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Study Director: Ron Shazer, MD Mirati Therapeutics Inc.
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Responsible Party: Mirati Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT05245500    
Other Study ID Numbers: 1719-001
First Posted: February 18, 2022    Key Record Dates
Last Update Posted: August 10, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mirati Therapeutics Inc.:
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
Additional relevant MeSH terms:
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Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Mesothelioma
Mesothelioma, Malignant
Nerve Sheath Neoplasms
Neurofibrosarcoma
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenoma
Neoplasms, Mesothelial
Pleural Neoplasms
Neoplasms, Nerve Tissue
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Fibrosarcoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue