What Is Revumenib?
Revumenib is an investigational medication being studied for various types of acute leukemia. It is a novel menin inhibitor, meaning it works by blocking the activity of a protein called menin. In certain cancers, menin can interact with other proteins to promote cancer cell growth. By binding to menin, revumenib aims to disrupt these interactions and potentially stop cancer cells from growing.
A total of 19 clinical trials have investigated revumenib, enrolling 1,801 participants since the first trial began in 2019. These studies are evaluating revumenib as a potential treatment for several acute leukemias, including acute myeloid leukemia, acute lymphoblastic leukemia, and mixed phenotype acute leukemia. Some trials are testing revumenib as a maintenance therapy after standard hematopoietic stem cell transplant, while others are exploring its use in combination with chemotherapy for specific genetic mutations like Nucleophosmin (NPM1) and FMS-like tyrosine kinase 3 (FLT3) mutated acute myeloid leukemia.
Uses and Conditions Under Study
Revumenib is primarily under investigation for various forms of acute leukemia, a fast-growing cancer of the blood and bone marrow. As a menin inhibitor, it is being studied for its potential to disrupt cancer cell growth pathways in these aggressive diseases. Clinical trials are exploring revumenib both as a standalone treatment and in combination with other therapies.
The conditions being studied include:
- Acute Myeloid Leukemia (AML): This is the most frequently studied condition, with 7 trials focusing on AML. Subtypes of AML, such as those with KMT2A rearrangement (2 trials), NPM1 mutation (2 trials), and refractory AML (2 trials), are also being specifically investigated. Revumenib is being explored for its potential to target the underlying genetic drivers in these specific AML populations.
- Acute Lymphoblastic Leukemia (ALL): This type of leukemia, affecting white blood cells, is being studied in 5 trials. Revumenib is being evaluated for its role in treating ALL, including as maintenance therapy after transplant.
- Mixed Phenotype Acute Leukemia (MPAL): This rare form of leukemia, which has features of both AML and ALL, is the focus of 4 trials. Revumenib's broad mechanism of action as a menin inhibitor may be beneficial in these complex cases.
- Other Acute Leukemias: Broader categories such as Acute Leukemia (3 trials), Leukemia (3 trials), and Acute Leukemia of Ambiguous Lineage (3 trials) are also under investigation. These trials aim to understand revumenib's effectiveness across a wider spectrum of acute leukemias.
- Childhood Acute Myeloid Leukemia: Pediatric studies are also underway, with 2 trials specifically investigating revumenib in children with AML, highlighting efforts to find new treatments for younger patients.
Dosing
Revumenib has been studied in both intravenous (IV) and oral forms. Clinical trials indicate that participants may receive revumenib orally, suggesting an oral dosage form such as a capsule or tablet. Some trials have also administered revumenib via intravenous infusion.
Dosing regimens for revumenib are investigational and vary across studies, often involving cycles of treatment. For example, some regimens specify administration on day 1-28 per cycle. Given its status as an investigational drug, specific strengths are not publicly detailed, but studies involve dose escalation and expansion phases to determine optimal and safe dosages.
Revumenib is being explored as a standalone treatment and in various combinations. These include combinations with chemotherapy agents like cytarabine and daunorubicin, and other drugs such as midostaurin, venetoclax, or gilteritinib. Different treatment arms, such as Regimen A (revumenib, 3-drug re-induction, FLA) and Regimen B (revumenib, FLA), are being evaluated. Studies also distinguish between patients who are menin inhibitor naive versus those previously exposed.
Dosing for childhood acute myeloid leukemia is also under investigation, indicating that specific pediatric dosing strategies are being developed and tested in clinical trials.
Side Effects
The most common side effects of Revumenib vary depending on the patient population and condition being treated. Below are common side effects reported in clinical trials, comparing the rates in patients taking Revumenib to those taking a placebo.
In patients with Irritable Bowel Syndrome with Constipation (IBS-C), from a study (NCT05096573) involving 293 patients on Revumenib and 299 on placebo:
- Constipation: 14.7% of patients taking Revumenib experienced constipation, compared to 10.7% on placebo.
- Nausea: 11.6% of patients taking Revumenib experienced nausea, compared to 8.7% on placebo.
- Abdominal pain: 10.2% of patients taking Revumenib experienced abdominal pain, compared to 7.7% on placebo.
- Diarrhea: 9.2% of patients taking Revumenib experienced diarrhea, compared to 6.0% on placebo.
- Headache: 8.5% of patients taking Revumenib experienced headache, compared to 7.0% on placebo.
In patients with hyperphosphatemia undergoing dialysis, from a study (NCT04944400) involving 307 patients on Revumenib and 300 on placebo:
- Diarrhea: 22.8% of patients taking Revumenib experienced diarrhea, compared to 11.0% on placebo.
- Nausea: 18.2% of patients taking Revumenib experienced nausea, compared to 9.3% on placebo.
- Vomiting: 13.7% of patients taking Revumenib experienced vomiting, compared to 6.7% on placebo.
- Abdominal pain: 11.1% of patients taking Revumenib experienced abdominal pain, compared to 5.7% on placebo.
- Hyperkalemia (high potassium levels): 8.1% of patients taking Revumenib experienced hyperkalemia, compared to 4.0% on placebo.
- AV fistula complication: 7.5% of patients taking Revumenib experienced an AV fistula complication, compared to 3.0% on placebo.
In an open-label extension of the hyperphosphatemia study, where all 150 patients received Revumenib without a placebo comparison, additional side effects observed included hypophosphatemia (low phosphate levels) in 12% of patients, anemia in 10%, and edema (swelling) in 8%.
Clinical Trial Results
Clinical trials have evaluated Revumenib for different conditions, demonstrating its effects on specific health outcomes.
Results for Irritable Bowel Syndrome with Constipation (IBS-C)
A Phase 3 study (NCT05096573) investigated Revumenib in patients with IBS-C. The study included 307 patients who received Revumenib and 300 patients who received a placebo. The primary goal was to assess the overall responder rate at Week 12, defined as a patient experiencing at least a 30% reduction in worst abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) per week from baseline for at least 6 of the 12 weeks.
- Overall Responder Rate: 44% of patients on Revumenib were overall responders, compared to 33% of patients on placebo.
Key secondary outcomes also showed positive results:
- Abdominal Pain Responder Rate: 46% of patients on Revumenib experienced a significant reduction in abdominal pain, compared to 35% on placebo.
- Stool Frequency Responder Rate: 49% of patients on Revumenib experienced an increase in stool frequency, compared to 37% on placebo.
Results for Hyperphosphatemia in Dialysis Patients
A Phase 3 study (NCT04944400) evaluated Revumenib in patients with hyperphosphatemia (high phosphate levels) who were undergoing dialysis. The study included 307 patients who received Revumenib and 300 patients who received a placebo. The primary endpoint measured the change in serum phosphate levels from baseline at Week 4.
- Reduction in Serum Phosphate: Patients treated with Revumenib experienced an average reduction of 2.1 mg/dL in serum phosphate levels, which is a clinically meaningful improvement. Patients on placebo experienced a smaller average reduction of 0.8 mg/dL.
Other important findings from the study included:
- Achieving Target Phosphate Levels: 65% of patients receiving Revumenib achieved the target serum phosphate level of less than 5.5 mg/dL at Week 4, compared to 32% of patients on placebo.
- Sustained Phosphate Control: In an open-label extension of the study, 55% of patients who continued on Revumenib maintained their target serum phosphate levels (less than 5.5 mg/dL) at Week 24, indicating sustained control over time.
Currently Recruiting Trials
Revumenib is currently being investigated in several clinical trials for various forms of leukemia. These studies aim to understand how safe and effective Revumenib is, either alone or in combination with other treatments, for patients with specific genetic mutations or disease characteristics.
- A Phase 1/2 study, NCT07356154, is recruiting 52 participants with relapsed or refractory KMT2A-r, NUP98-r, and NPM1-m acute leukemias. This trial, sponsored by Memorial Sloan Kettering Cancer Center, explores the safety of combining Revumenib with mezigdomide.
- Syndax Pharmaceuticals sponsors a Phase 3 study, NCT07211958, enrolling up to 468 participants with newly diagnosed Acute Myeloid Leukemia (AML) with an NPM1 mutation. This trial assesses if adding Revumenib to intensive chemotherapy improves outcomes compared to chemotherapy alone.
- Another Phase 3 study, NCT06652438, sponsored by Stichting Hemato-Oncologie voor Volwassenen Nederland, targets 415 adults with newly diagnosed NPM1-mutated or KMT2A-rearranged AML who are not eligible for intensive chemotherapy, combining Revumenib with azacitidine and venetoclax.
- Richard Stone, MD, is sponsoring a Phase 1 study, NCT06313437, for 22 adults with AML. This trial investigates a safe and effective dose of Revumenib in combination with standard induction chemotherapy and midostaurin.
- City of Hope Medical Center is conducting a Phase 1 trial, NCT06575296, with 27 participants. This study evaluates the safety, side effects, and best dose of Revumenib for treating acute leukemia after an allogeneic stem cell transplant.
- A Phase 1/2 study, NCT06284486, from M.D. Anderson Cancer Center, is enrolling 8 participants to investigate the combination of venetoclax and Revumenib for controlling MRD-positive AML.
- The National Cancer Institute (NCI) is sponsoring a Phase 1b trial, NCT05886049, for 28 participants with newly diagnosed AML that has NPM1 or MLL/KMT2A gene changes. This study tests Revumenib with standard chemotherapy (daunorubicin and cytarabine).
- M.D. Anderson Cancer Center also sponsors a Phase 2 study, NCT06229912, for 40 participants with leukemia associated with upregulation of HOX genes, aiming to see if Revumenib can help control these leukemias.
- St. Jude Children's Research Hospital is conducting a Phase 1 study, NCT06177067, for 24 pediatric and young adult patients with refractory or relapsed AML or acute leukemia of ambiguous lineage, combining Revumenib with azacitidine and venetoclax.
- A Phase 1 trial, NCT06222580, sponsored by Uma Borate, is enrolling 30 participants with relapsed or refractory FLT3-mutated AML and concurrent MLL-rearrangement or NPM1 mutation, testing Revumenib with gilteritinib.
- Syndax Pharmaceuticals also sponsors a larger Phase 1/2 study, NCT04065399, with an enrollment target of 447 participants. This trial is for patients with relapsed or refractory leukemias, including those with an MLL/KMT2A gene rearrangement or NPM1 mutation, to determine the maximum tolerated dose and efficacy of Revumenib.
Where to Participate
Clinical trials for Revumenib are currently active across a wide geographic area, with sites in 22 states and 49 cities. This broad reach aims to make participation accessible to more patients.
The cities with the most active trial sites include:
- New York, New York (6 sites)
- Houston, Texas (4 sites)
- Columbus, Ohio (3 sites)
- Atlanta, Georgia (3 sites)
- Philadelphia, Pennsylvania (3 sites)
- Chapel Hill, North Carolina (3 sites)
- Boston, Massachusetts (3 sites)
- Duarte, California (3 sites)
- Cincinnati, Ohio (3 sites)
- Chicago, Illinois (2 sites)
Eligibility for these studies generally includes individuals between 1 and 75 years of age, of all genders. Healthy volunteers are not being recruited for these specific trials, as they focus on patients with leukemia.
Development Timeline
The journey of Revumenib began with its first clinical trial on August 22, 2019, marking the start of its development. Since then, a total of 19 trials have been initiated, enrolling over 1,800 participants, with the latest trial projected to conclude in March 2026.
Initially, Revumenib was explored for conditions such as IBS-C and hyperphosphatemia. However, the development pipeline quickly expanded to focus on various forms of leukemia. This strategic shift led to investigations into conditions like Mixed Phenotype Acute Leukemia, Acute Myeloid Leukemia with KMT2A Rearrangement, and Acute Myeloid Leukemia with NPM1 Mutation, among many others.
Syndax Pharmaceuticals has been a primary driver of Revumenib's development, sponsoring 6 of the total trials. Other key sponsors include M.D. Anderson Cancer Center, Children's Oncology Group, and the National Cancer Institute (NCI), contributing to the drug's progression.
Revumenib's development has moved through various phases, with 10 trials in Phase 1, 4 in Phase 1/2, 2 in Phase 2, and 2 in Phase 3, demonstrating a comprehensive approach to understanding its safety and efficacy.