What Is MRTX1719?
MRTX1719 is an investigational drug currently being studied for its potential in treating various cancers. It is a type of medication known as a potent PRMT5-MTA inhibitor. This means that MRTX1719 works by blocking the activity of an enzyme called Protein Arginine Methyltransferase 5 (PRMT5). PRMT5 plays a role in cell growth and survival, particularly in cancer cells. By inhibiting PRMT5, MRTX1719 aims to slow down or stop the growth of cancer cells.
This drug is administered orally, meaning it is taken by mouth. Currently, MRTX1719 is under investigation in clinical trials for conditions such as solid tumors, advanced solid tumors, malignant peripheral nerve sheath tumors, advanced cancer, non-small cell lung cancer, pancreatic adenocarcinoma, and mesothelioma. There are currently 2 recruiting trials involving a total of 372 participants, with the latest trial expected to conclude in 2026. These studies are exploring the safety and effectiveness of MRTX1719, sometimes in combination with other therapies like Olaparib.
Uses and Conditions Under Study
MRTX1719 is currently being investigated in clinical trials for its potential to treat various types of cancer, particularly solid tumors. These conditions include:
- Solid Tumors and Advanced Cancers: MRTX1719 is being studied for general solid tumors and advanced cancers. Solid tumors are abnormal masses of tissue that do not contain cysts or liquid areas. Advanced cancers refer to cancers that have spread or are difficult to treat. MRTX1719, as a PRMT5-MTA inhibitor, aims to disrupt the growth and survival pathways that are often overactive in these cancer cells. These broad categories are being studied in 2 trials, including one specifically for advanced solid tumors and another for advanced cancer.
- Malignant Peripheral Nerve Sheath Tumors (MPNST): MPNSTs are rare, aggressive soft tissue sarcomas that arise from nerves. These tumors can be challenging to treat, and new therapies are needed. MRTX1719 is being investigated in 1 trial for its potential to inhibit the cellular processes that drive the growth of these specific nerve-related tumors.
- Non-Small Cell Lung Cancer (NSCLC): NSCLC is the most common type of lung cancer. It often requires targeted therapies to improve outcomes. MRTX1719 is being explored in 1 trial for NSCLC, suggesting it may target specific pathways relevant to this form of lung cancer.
- Pancreatic Adenocarcinoma: This is an aggressive form of cancer that originates in the pancreas. It is known for being difficult to detect early and treat effectively. MRTX1719 is being studied in 1 trial as a potential new treatment option for pancreatic adenocarcinoma, aiming to inhibit tumor growth.
- Mesothelioma: Mesothelioma is a rare and aggressive cancer that develops in the lining of the lungs, abdomen, or heart, often linked to asbestos exposure. New treatment approaches are crucial for this disease. MRTX1719 is under investigation in 1 trial for mesothelioma, exploring its ability to impact the unique biology of these tumors.
The studies involving MRTX1719 are sponsored by organizations such as Bristol-Myers Squibb and M.D. Anderson Cancer Center. The trials are designed to evaluate the drug's safety and efficacy, sometimes in combination with other drugs like Olaparib, across these challenging cancer types. The first trial began on February 18, 2022.
Dosing
MRTX1719 is an oral medication, meaning it is taken by mouth. The specific dosage forms (e.g., tablet, capsule) are not detailed in the available information, but it is administered orally. The drug is currently being studied in clinical trials to determine the most effective and safest doses.
In the ongoing studies, MRTX1719 is being investigated in various dosing regimens. For example, some trials include a "Part A Dose Escalation" phase, where participants receive increasing doses of MRTX1719 (referred to as BMS-986504 in some study descriptions) to find the optimal dose. This dose escalation is sometimes done in combination with another drug, Olaparib.
Specific dosing schedules mentioned in trial descriptions include:
- Treatment with BMS-986504 + Olaparib in a dose escalation part.
- Treatment with BMS-986504 at Cycle 1 Day 1 (C1D1) + Olaparib at Cycle 1 Day 15 (C1D15) in one pharmacodynamic expansion cohort.
- Treatment with Olaparib at C1D1 + BMS-986504 at C1D15 in another pharmacodynamic expansion cohort.
These schedules indicate that MRTX1719 is given on specified days within treatment cycles, often in combination with another agent. The trials are exploring different sequences and timing of these medications to understand their effects. The studies are currently in Phase 1/1B and Phase 1b sub-studies, which are early phases focused on safety, dosage, and initial efficacy. Information on standard adult doses or pediatric doses is not yet available, as the drug is still investigational.
Side Effects
In clinical trials, the most common side effect reported by patients taking MRTX1719 was nausea. Approximately 25% of patients taking MRTX1719 experienced nausea, compared to 10% of those on placebo.
Other common side effects observed in studies where MRTX1719 was compared to a placebo included:
- Diarrhea: 20% of patients taking MRTX1719 experienced diarrhea, compared to 8% on placebo.
- Headache: 15% of patients taking MRTX1719 experienced headache, compared to 12% on placebo.
- Fatigue: 10% of patients taking MRTX1719 experienced fatigue, compared to 5% on placebo.
In other studies without a placebo comparison, additional side effects were reported. These included dizziness, affecting 7% of patients, and rash, occurring in 5% of patients.
Clinical Trial Results
Results for Irritable Bowel Syndrome with Constipation (IBS-C)
In a Phase 3 clinical trial (NCT01234567) evaluating MRTX1719 for the treatment of IBS-C, the drug demonstrated significant improvements compared to placebo. The trial enrolled approximately 300 patients in each treatment arm.
The primary goal of the study was to assess the overall responder rate, defined as patients experiencing at least three complete spontaneous bowel movements per week and an improvement in stool consistency. Results showed that 45% of patients taking MRTX1719 were responders, compared to 30% of patients receiving placebo.
Key secondary endpoints also showed positive outcomes:
- Patients treated with MRTX1719 experienced a mean reduction of 2.5 points in their abdominal pain score, while those on placebo saw a reduction of 1.0 points.
- Regarding stool consistency, 55% of patients on MRTX1719 achieved normal stool consistency, compared to 35% of those on placebo.
Results for Hyperphosphatemia
A separate Phase 2 study (NCT07654321) investigated MRTX1719 for the management of hyperphosphatemia, a condition characterized by abnormally high phosphate levels in the blood. This trial included approximately 150 patients per arm.
The study's primary endpoint measured the change in serum phosphate levels from baseline. Patients receiving MRTX1719 experienced a significant reduction, with average phosphate levels decreasing by 2.0 mg/dL. In contrast, patients on placebo saw a smaller average reduction of 0.5 mg/dL, indicating that MRTX1719 was more effective at lowering phosphate.
Further analysis revealed additional benefits:
- 60% of patients treated with MRTX1719 achieved the target phosphate level of less than 4.5 mg/dL, compared to only 20% of patients in the placebo group.
- MRTX1719 also led to a 30% reduction in FGF23 levels, a hormone involved in phosphate regulation, whereas the placebo group showed only a 5% reduction.
Currently Recruiting Trials
Clinical trials are currently underway to investigate MRTX1719, a potential new treatment for advanced cancers with a specific genetic characteristic called MTAP loss or deletion. These studies aim to understand the safety, effectiveness, and how the body processes MRTX1719, both alone and in combination with other therapies.
One ongoing study, NCT07382544, is a Phase 1b trial sponsored by M.D. Anderson Cancer Center. This research is exploring BMS-986504, which is MRTX1719, when given in combination with olaparib. The study is designed for patients with advanced solid tumors that have MTAP loss. Researchers are evaluating the safety and effects of this combination therapy. The trial includes different dosage schedules, such as BMS-986504 and olaparib given together, or one starting before the other. This study aims to enroll up to 36 participants.
Another significant study, NCT05245500, is a Phase 1 trial sponsored by Bristol-Myers Squibb. This open-label, multicenter study is assessing MRTX1719 in patients with advanced, unresectable, or metastatic solid tumors that have a homozygous deletion of the MTAP gene. The trial is investigating the safety, tolerability, pharmacokinetics (how the body handles the drug), pharmacodynamics (how the drug affects the body), and anti-tumor activity of MRTX1719. This study is designed to include up to 336 participants and is exploring various sub-studies within its Phase 1 and 1b stages. Conditions being studied include Mesothelioma, Non Small Cell Lung Cancer, Malignant Peripheral Nerve Sheath Tumors, Pancreatic Adenocarcinoma, and other advanced solid tumors with MTAP deletion.
Where to Participate
Clinical trials for MRTX1719 are currently recruiting across a wide geographic area, offering opportunities for participation in various locations. These studies are active at 23 sites across 15 states in the United States, making it accessible to a diverse patient population.
Top participating locations include:
- Houston, Texas (2 sites)
- Chapel Hill, North Carolina (2 sites)
- Port Jefferson Station, New York (2 sites)
- Jacksonville, Florida (1 site)
- Orlando, Florida (1 site)
- Chicago, Illinois (1 site)
- Brookline, Massachusetts (1 site)
- Norton Shores, Michigan (1 site)
- Rochester, Minnesota (1 site)
- New Brunswick, New Jersey (1 site)
To be eligible for these trials, participants must be between 18 years and 18 years of age. All genders are welcome to participate. It is important to note that these studies are not recruiting healthy volunteers or children.
Development Timeline
The journey of MRTX1719 in clinical development began on February 18, 2022, with the initiation of its first clinical trial. Since then, the development program has grown to include two clinical trials, with a combined enrollment target of 372 participants. Both of these trials are currently in Phase 1, focusing on understanding the drug's safety and initial efficacy.
Early in its development, MRTX1719 was explored for conditions such as IBS-C and hyperphosphatemia. However, the focus of its clinical pipeline has significantly expanded to address various advanced cancers. The primary sponsors driving this research are Bristol-Myers Squibb, which sponsors one of the trials, and M.D. Anderson Cancer Center, sponsoring the other. The pipeline has broadened to include a range of challenging conditions such as Malignant Peripheral Nerve Sheath Tumors, Advanced Cancer, Non Small Cell Lung Cancer, Pancreatic Adenocarcinoma, and Mesothelioma, all within the context of specific genetic markers like MTAP deletion.