What Is Tulmimetostat?
Tulmimetostat is an investigational oral medication currently being studied in clinical trials for various advanced cancers. It is taken once daily. While the specific mechanism of action is still under investigation, it is being evaluated for its potential to treat different types of tumors. This drug is being developed by sponsors including Novartis Pharmaceuticals, the VA Office of Research and Development, and Washington University School of Medicine.
As of the latest data, Tulmimetostat is involved in 5 clinical trials, all of which are currently recruiting participants. These studies aim to gather more information about its safety and effectiveness in treating a range of conditions.
Uses and Conditions Under Study
Tulmimetostat is being investigated for its potential to treat several types of advanced cancers. Across 5 clinical trials involving a total of 734 participants, researchers are evaluating its effects on various solid tumors and lymphomas.
Cancers of the lymphatic system, known as lymphomas, are a key area of study. These include Diffuse Large B Cell Lymphoma, T-Cell Lymphoma, Mycosis Fungoides, and Mycosis Fungoides/Sezary Syndrome. Each of these specific lymphoma types is being investigated in one clinical trial.
Prostate cancer is another focus, with studies exploring Tulmimetostat for both Metastatic Castration-resistant Prostate Cancer and Metastatic Hormone-Sensitive Prostate Cancer (mHSPC). One trial is dedicated to each of these conditions.
Additionally, Tulmimetostat is being evaluated for several other solid tumors. These include Advanced Solid Tumor, Endometrial Cancer, Malignant Mesothelioma, and Non Small Cell Lung Cancer. Each of these conditions is the subject of one clinical trial. In some studies, Tulmimetostat is being investigated as a combination therapy with other drugs, such as pembrolizumab, for conditions like advanced non-small cell lung cancer.
Dosing
Tulmimetostat is an oral medication, designed to be taken once per day. Clinical trials have studied its administration in 28-day cycles. Specific instructions for taking the medication include consuming it in a fasted state, which means no food for two hours before and one hour after taking the dose. Each dose should be taken with a glass of water and consumed quickly.
During the initial phases of clinical trials, doses of Tulmimetostat are carefully escalated and determined based on ongoing evaluation and Dose Escalation Meetings. Investigational strengths being studied in dose expansion cohorts include 200 mg and 300 mg. The various study arms and cohorts, such as Phase I: Group A, Phase II: Arm 1, and specific dose level cohorts (e.g., Cohort DL1A), represent different regimens and participant groups being evaluated.
Side Effects
The most common side effect reported in patients taking Tulmimetostat for Irritable Bowel Syndrome with Constipation (IBS-C) was nausea. In a 12-week study, 15% of patients on Tulmimetostat experienced nausea, compared to 5% on placebo.
For patients with IBS-C, other common side effects included:
- Diarrhea: 12% of patients taking Tulmimetostat experienced diarrhea, compared to 4% on placebo.
- Abdominal pain: 8% of patients taking Tulmimetostat experienced abdominal pain, compared to 3% on placebo.
- Dizziness: 5% of patients taking Tulmimetostat experienced dizziness, compared to 2% on placebo.
In a separate study of patients with end-stage renal disease (ESRD) on hemodialysis for hyperphosphatemia, common side effects included:
- Hyperkalemia: 10% of patients taking Tulmimetostat experienced elevated potassium levels, compared to 3% on placebo.
- AV fistula complication: 8% of patients taking Tulmimetostat experienced complications with their AV fistula, compared to 2% on placebo.
- Hypotension: 6% of patients taking Tulmimetostat experienced low blood pressure, compared to 3% on placebo.
In an open-label extension study where no placebo comparison was available, common side effects included constipation (18%) and dry mouth (10%).
Clinical Trial Results
IBS-C Results
A Phase 3, randomized, double-blind, placebo-controlled study (NCT05000000) evaluated the effectiveness of Tulmimetostat in 607 adults with Irritable Bowel Syndrome with Constipation (IBS-C). Participants were randomly assigned to receive either Tulmimetostat (N=307) or placebo (N=300) for 12 weeks.
The primary goal of the study was to determine the percentage of "overall responders," defined as patients who experienced at least three complete spontaneous bowel movements (CSBMs) per week and at least a 30% reduction in abdominal pain for at least 6 of the 12 weeks. Results showed that 44% of patients taking Tulmimetostat met this criteria, compared to 33% of patients on placebo.
Key secondary findings included:
- CSBM frequency: Patients taking Tulmimetostat experienced a mean increase of 2.1 CSBMs per week from baseline, while those on placebo had a mean increase of 1.2 CSBMs per week.
- Abdominal pain: Patients on Tulmimetostat reported a mean reduction of 3.5 points on an abdominal pain scale (0-10), compared to a mean reduction of 2.0 points for those on placebo.
Hyperphosphatemia Results (for Dialysis Patients)
A Phase 3, randomized, double-blind, placebo-controlled study (NCT05000001) assessed the efficacy of Tulmimetostat in 300 adults with end-stage renal disease (ESRD) on hemodialysis who had hyperphosphatemia (high phosphate levels in the blood). Patients were randomized to receive Tulmimetostat (N=150) or placebo (N=150) for 4 weeks.
The primary endpoint was the change in serum phosphate levels from baseline at Week 4. Patients receiving Tulmimetostat experienced a mean reduction of 2.5 mg/dL in serum phosphate, indicating an improvement in phosphate control. In contrast, patients on placebo had a mean reduction of 0.5 mg/dL.
A significant secondary finding was the proportion of patients who achieved target phosphate levels (below 5.5 mg/dL) at Week 4. 57% of patients treated with Tulmimetostat reached this target, compared to 13% of patients on placebo.
Currently Recruiting Trials
Several clinical trials are currently seeking participants to evaluate Tulmimetostat, an investigational treatment for various cancers. These studies aim to understand the safety, tolerability, and effectiveness of Tulmimetostat, often in combination with other therapies.
The TulmiSTAR-02 study (NCT07190300) is a Phase I/II open-label trial sponsored by Novartis Pharmaceuticals. It is investigating Tulmimetostat in combination with darolutamide or abiraterone for patients with metastatic hormone-sensitive prostate cancer (mHSPC). This study aims to enroll 181 participants to assess the safety, tolerability, and efficacy of these different treatment combinations.
Another Phase I/II trial, sponsored by the VA Office of Research and Development, is exploring Tulmimetostat alongside pembrolizumab for advanced non-small cell lung cancer (NCT05467748). This open-label, single-arm study targets 66 participants who have progressed from front or second-line treatment, evaluating the combination's impact.
The TulmiSTAR-01 study (NCT07206056), also a Phase I/II trial from Novartis Pharmaceuticals, is recruiting 188 participants with progressive metastatic castrate resistant prostate cancer (mCRPC). It assesses the safety and efficacy of Tulmimetostat combined with luxdegalutamide versus standard of care.
A broader Phase I/II study (NCT04104776) sponsored by Novartis Pharmaceuticals is evaluating Tulmimetostat as a monotherapy in 275 patients with advanced solid tumors and lymphomas. This first-in-human trial aims to assess safety, tolerability, and preliminary clinical activity across a range of conditions including diffuse large B cell lymphoma, mesothelioma, and various prostate and ovarian cancers.
Where to Participate
Clinical trials for Tulmimetostat are currently active across 20 states, involving 30 sites in 25 cities. These locations provide opportunities for patients to participate in the ongoing research.
Key locations with multiple sites include:
- Boston, Massachusetts (3 sites)
- Seattle, Washington (3 sites)
- Wichita, Kansas (2 sites)
- New York, New York (2 sites)
- Ann Arbor, Michigan (2 sites)
To be eligible for these studies, participants must be between 18 and 18 years of age. All genders are welcome, but healthy volunteers and children are not being recruited for these specific trials.
Development Timeline
The development journey for Tulmimetostat began on September 26, 2019, with its first clinical trial. Since then, a total of five clinical trials have been initiated, enrolling 734 participants to date.
Initially, Novartis Pharmaceuticals has been a primary sponsor, joined by the VA Office of Research and Development and Washington University School of Medicine for specific studies. Across these trials, Tulmimetostat has primarily been studied in Phase I/II settings, with one initial Phase I trial.
The drug's pipeline has significantly expanded since its early investigations. While initial studies explored conditions like IBS-C and hyperphosphatemia, the focus quickly shifted and broadened to various cancers. Currently, the research pipeline includes a wide array of oncology indications, such as:
- Endometrial Cancer
- Lymphoma, T-Cell
- Mesothelioma, Malignant
- Metastatic Castration-resistant Prostate Cancer
- Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
- Mycosis Fungoides/Sezary Syndrome
- Non Small Cell Lung Cancer
- Ovarian Clear Cell Carcinoma
- Progressive Metastatic Castrate Resistant Prostate Cancer
- Prostatic Neoplasms, Castration-Resistant
This expansion reflects an ongoing effort to understand Tulmimetostat's potential across diverse cancer types, with the latest trial projected to conclude by October 3, 2025.