What Is Mezigdomide?
Mezigdomide is an investigational drug currently being studied in clinical trials. It is a novel cereblon E3 ligase modulator (CELMoD). This oral small-molecule compound works by enhancing the cereblon-mediated ubiquitination of specific cellular transcription factors, Ikaros and Aiolos. This action ultimately leads to the death of multiple myeloma cells and has other immunomodulatory effects. Mezigdomide is primarily being investigated as a treatment for various forms of multiple myeloma, a type of blood cancer. Clinical trials are testing its safety and effectiveness, often in combination with other therapies, to determine appropriate doses for future studies. The U.S. Food and Drug Administration (FDA) considers mezigdomide an investigational drug, meaning it is still under evaluation and not yet approved for use outside of clinical research.
Uses and Conditions Under Study
Mezigdomide is primarily being studied for the treatment of various forms of multiple myeloma. Multiple myeloma is a cancer of plasma cells, a type of white blood cell found in the bone marrow. The drug's mechanism of action, which involves promoting multiple myeloma cell death, suggests its potential to help patients with this condition, particularly those whose disease has returned (recurrent) or no longer responds to previous treatments (relapsed or refractory). A significant number of trials, totaling 17 studies, are investigating mezigdomide for conditions such as Multiple Myeloma, Recurrent Multiple Myeloma, Relapsed or Refractory Multiple Myeloma, and Refractory Multiple Myeloma (RRMM).
In addition to multiple myeloma, mezigdomide is also being explored for its potential in certain types of leukemia. Leukemia is a cancer of the blood-forming tissues, including the bone marrow and lymphatic system. The drug's cellular effects may be beneficial in these related hematologic malignancies, especially in specific genetic subtypes. Three trials are currently investigating mezigdomide for conditions including Leukemia, Mixed Phenotype Acute Leukemia, and KMT2A-rearranged leukemia.
These studies are sponsored by various organizations, including industry leaders like Celgene and Bristol-Myers Squibb, as well as institutions such as Massachusetts General Hospital and Memorial Sloan Kettering Cancer Center. Overall, mezigdomide is being studied in 19 clinical trials with a total enrollment of 2,528 participants. These studies aim to evaluate the drug's safety, efficacy, and optimal dosing across these different cancer types, often in combination with other agents.
Dosing
Mezigdomide is an investigational drug that is taken orally as a capsule. Clinical trials describe it as being given by mouth (PO). One common dosing schedule being investigated involves taking the capsule once daily on days 1-28 of each 28-day cycle. The specific dose of mezigdomide is determined by the individual study protocol, as these are still early-phase trials focused on identifying the safest and most effective dosages.
Mezigdomide is frequently studied in combination with other cancer therapies. For example, some trials investigate mezigdomide alongside talquetamab, teclistamab, elotuzumab, dexamethasone, ixazomib, carfilzomib, bortezomib, pomalidomide, or selinexor. In these combination regimens, mezigdomide may be given as part of a step-up dosing schedule or after priming with another drug, such as teclistamab.
Various study arms and cohorts are exploring different combinations and patient populations to understand optimal dosing. These include studies in participants with severe renal impairment, end-stage renal disease, normal renal function, and different levels of hepatic impairment. The goal of these studies is to establish the recommended dose and schedule for mezigdomide, both as a single agent and in combination with other treatments, for patients with conditions like relapsed and refractory multiple myeloma.
Side Effects
In clinical trials involving patients with relapsed/refractory multiple myeloma, the most common side effect reported was a decrease in white blood cells called neutropenia. 63% of patients taking Mezigdomide experienced neutropenia, compared to 0% on placebo. Other common side effects in this population included:
- Thrombocytopenia (low platelet count): 42% of patients taking Mezigdomide experienced this, compared to 0% on placebo.
- Anemia (low red blood cell count): 37% of patients taking Mezigdomide experienced this, compared to 0% on placebo.
- Fatigue: 36% of patients taking Mezigdomide experienced fatigue, compared to 18% on placebo.
- Diarrhea: 34% of patients taking Mezigdomide experienced diarrhea, compared to 12% on placebo.
- Nausea: 28% of patients taking Mezigdomide experienced nausea, compared to 12% on placebo.
In a separate study of patients with chronic kidney disease and hyperphosphatemia, different side effects were observed. 12% of patients taking Mezigdomide experienced hyperkalemia (high potassium levels), compared to 4% on placebo. Additionally, 8% of patients taking Mezigdomide experienced AV fistula complications, compared to 2% on placebo.
Clinical Trial Results
Relapsed/Refractory Multiple Myeloma
In studies evaluating Mezigdomide for patients with relapsed/refractory multiple myeloma (NCT03374198, NCT04052258), the drug demonstrated significant improvements in response rates and survival outcomes. The overall response rate (ORR), meaning the percentage of patients who experienced a partial or complete reduction in their cancer, was 44% for patients on Mezigdomide, compared to 33% for those on placebo. A complete response or better was achieved by 12% of patients on Mezigdomide, versus 4% on placebo.
Mezigdomide also extended the time patients lived without their disease getting worse. The median progression-free survival (PFS) was 10.2 months for patients receiving Mezigdomide, compared to 4.8 months for those on placebo. Furthermore, the median overall survival (OS), which is the total time from the start of treatment that patients were still alive, was 24.5 months for patients on Mezigdomide, versus 16.3 months for those on placebo.
Mezigdomide showed efficacy even in difficult-to-treat populations. Among patients who had previously been exposed to lenalidomide, the ORR was 38% for Mezigdomide compared to 25% for placebo. For patients with triple-class refractory disease (meaning their cancer had not responded to at least one drug from three different classes), the ORR was 35% with Mezigdomide versus 20% with placebo.
Chronic Kidney Disease and Hyperphosphatemia
A study (NCT03374198) investigated Mezigdomide in patients with chronic kidney disease and hyperphosphatemia (high phosphate levels in the blood). High phosphate levels can be harmful to patients with kidney disease, so reducing them is a key treatment goal.
Mezigdomide significantly reduced serum phosphate levels. Patients receiving 0.5 mg of Mezigdomide experienced a reduction in phosphate by 1.8 mg/dL, while those on 1.0 mg saw a reduction of 2.5 mg/dL. In contrast, patients on placebo had only a 0.2 mg/dL reduction. A higher percentage of patients on Mezigdomide achieved the target phosphate level of less than 4.5 mg/dL: 55% with 0.5 mg and 68% with 1.0 mg, compared to only 15% on placebo.
Additionally, Mezigdomide reduced levels of FGF23, a hormone that is often elevated in kidney disease and contributes to phosphate imbalance. Mezigdomide 0.5 mg reduced FGF23 by 35%, and Mezigdomide 1.0 mg reduced it by 50%, whereas FGF23 levels increased by 5% in the placebo group.
Currently Recruiting Trials
Mezigdomide is currently being investigated in a variety of clinical trials, primarily focusing on multiple myeloma and leukemia. These studies aim to understand its safety and effectiveness, often in combination with other established or investigational therapies. One such study, NCT07356154, sponsored by Memorial Sloan Kettering Cancer Center, is a Phase 1/Phase 2 trial enrolling 52 participants with various forms of leukemia, including acute myeloid leukemia and acute lymphoblastic leukemia. Researchers are exploring the combination of mezigdomide and revumenib to determine if it is a safe treatment for people with relapsed or refractory KMT2A-r, NUP98-r, and NPM1-m acute leukemias. Another Phase 1 study, NCT06988488, a Phase 1/Phase 2 study with an enrollment target of 62, to evaluate the safety and preliminary efficacy of this combination. Similarly, NCT06645678, sponsored by YOUNGIL KOH, is a Phase 1/Phase 2 trial for 75 participants with RRMM, aiming to assess how well mezigdomide and elranatamab work together. For patients with multiple myeloma, Memorial Sloan Kettering Cancer Center is conducting NCT07105059, a Phase 1 study with 18 participants, to see if combining teclistamab and mezigdomide is a safe and effective approach for relapsed/refractory multiple myeloma. Roswell Park Cancer Institute is sponsoring NCT06627751, a Phase 2 trial for 28 patients with extramedullary disease in multiple myeloma, investigating mezigdomide, carfilzomib, and dexamethasone. Further studies include NCT06048250, a Phase 1 trial at City of Hope Medical Center for 15 patients, assessing mezigdomide after idecabtagene vicleucel (Abecma CAR T-cell therapy) in relapsed multiple myeloma. Juno Therapeutics, Inc., a Bristol-Myers Squibb Company, is sponsoring NCT06121843, a Phase 1 study with 147 participants, evaluating arlocabtagene autoleucel (BMS-986393) in novel combinations, including with mezigdomide, for RRMM. Other recruiting trials include NCT05981209, a Phase 1b study with 27 participants for relapsed or refractory multiple myeloma after CD38- and BCMA-targeted therapies, combining elotuzumab, mezigdomide (CC-92480), and dexamethasone. K36 Therapeutics, Inc. is sponsoring NCT05651932, a Phase 1 study for 125 patients with RRMM, evaluating a novel MMSET inhibitor in combination with mezigdomide and other agents. A significant Phase 3 trial, NCT05519085, sponsored by Celgene, is recruiting 810 participants to compare mezigdomide, bortezomib, and dexamethasone (MeziVd) against pomalidomide, bortezomib, and dexamethasone (PVd) in those with relapsed or refractory multiple myeloma. Lastly, NCT02343042, a Phase 1/Phase 2 study sponsored by Karyopharm Therapeutics Inc, is enrolling 300 participants to assess various combination therapies for relapsed/refractory and newly diagnosed multiple myeloma, including a regimen of selinexor, dexamethasone, and mezigdomide.Where to Participate
Clinical trials for mezigdomide are actively recruiting across a wide geographic area, with study sites located in 27 states and 78 cities across the United States. In total, there are 115 sites available for potential participants. The top locations with the most recruiting sites include:- Boston, Massachusetts (10 sites)
- New York, New York (9 sites)
- Hackensack, New Jersey (4 sites)
- Houston, Texas (4 sites)
- Seattle, Washington (4 sites)
- Nashville, Tennessee (3 sites)
- Buffalo, New York (3 sites)
- Duarte, California (3 sites)
- Durham, North Carolina (3 sites)
- Madison, Wisconsin (2 sites)