Advanced Solid Tumor, Malignant Peripheral Nerve Sheath Tumors, Mesothelioma, Non Small Cell Lung Cancer, Pancreatic Adenocarcinoma, Solid Tumor
Conditions
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
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.
Interventions
DRUGMRTX1719
MRTX1719 is a potent PRMT5-MTA inhibitor. Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Patients who Experience Dose-Limiting Toxicity | 21 days |
| Number of patients who experience a treatment-related adverse event | Up to 2 years |
| Objective response rate (ORR) | 2 years |
| Duration of response (DOR) | 2 years |
| Progression free survival (PFS) | 2 years |
| Overall survival (OS) | 2 years |
| Number of Patients With Clinically Significant Laboratory Assessments | Up to 4 years |
Secondary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration versus time curve (AUC) | Up to 4 days |
| Time to achieve maximal plasma concentration (Tmax) | Up to 4 days |
| Maximum observed plasma concentration (Cmax) | Up to 4 days |
| Terminal elimination half-life (t1/2) | Up to 4 days |
| Apparent total plasma clearance when dosed orally (CL/F) | Up to 4 days |
| Apparent volume of distribution when dosed orally (Vz/F) | Up to 4 days |
Countries
United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed