What Is Iberdomide?
Iberdomide is a drug currently under investigation in clinical trials for various cancers. It is being studied for its potential antitumor activity, particularly in patients with multiple myeloma that has returned after treatment (relapsed) or has not responded to previous therapies (refractory). Clinical trials are evaluating iberdomide both as a standalone treatment and in combination with other medications.
There are currently 35 clinical trials involving iberdomide, with a total enrollment of 5,185 participants. These studies began in 2020 and are projected to continue until at least 2026. Researchers are assessing the safety, side effects, and effectiveness of iberdomide across different patient populations and disease stages.
Uses and Conditions Under Study
Iberdomide is primarily being investigated for the treatment of various blood cancers, with a significant focus on multiple myeloma. This type of cancer affects plasma cells in the bone marrow. Iberdomide is being studied in 32 trials for conditions including Multiple Myeloma, Refractory Multiple Myeloma, Recurrent Multiple Myeloma, Relapsed Multiple Myeloma, and Plasma Cell Myeloma. These trials aim to evaluate iberdomide's efficacy in patients whose disease has progressed or returned after prior treatments, sometimes as a maintenance therapy after other intensive treatments like CAR-T cell therapy.
Beyond multiple myeloma, iberdomide is also being explored for its potential in other cancers. One trial is investigating its use in Non-Hodgkin Lymphoma, a type of cancer that originates in white blood cells called lymphocytes. Additionally, iberdomide is being studied in 4 trials for pediatric solid tumors, specifically Recurrent Ganglioneuroblastoma, Refractory Ganglioneuroblastoma, Recurrent Neuroblastoma, and Refractory Neuroblastoma. These studies seek to understand how iberdomide might help in treating these challenging cancers that have either returned or not responded to standard therapies.
Dosing
Iberdomide is being studied in several different dosage forms and administration routes in clinical trials. Patients may receive iberdomide orally, either as a powder or a capsule. It is also being investigated for administration via intravenous (IV) infusion and subcutaneously (SQ), meaning it is injected under the skin. The specific method of delivery depends on the trial design and the combination therapies being evaluated.
The strengths of iberdomide being studied vary across trials, often referred to as "Dose Level 1," "Dose Level 2," or specific "Dose" numbers, indicating a range of investigational strengths. These doses are carefully determined in dose-escalation studies to find the safest and most effective amount, especially when iberdomide is given in combination with other drugs like dexamethasone, talquetamab, or elotuzumab. For example, some trials evaluate iberdomide in combination with low-dose cyclophosphamide and dexamethasone, while others explore regimens such as iberdomide plus daratumumab and dexamethasone.
Side Effects
In a clinical trial for irritable bowel syndrome with constipation (IBS-C) (NCT04746654), the most common side effect reported by patients taking Iberdomide was nausea. 11.6% of patients taking Iberdomide experienced nausea, compared to 6.4% on placebo. Other common side effects included:
- Diarrhea: 10.9% of patients on Iberdomide compared to 6.0% on placebo.
- Abdominal pain: 5.8% of patients on Iberdomide compared to 4.7% on placebo.
- Vomiting: 5.1% of patients on Iberdomide compared to 2.7% on placebo.
- Headache: 4.4% of patients on Iberdomide compared to 4.0% on placebo.
- Fatigue: 3.8% of patients on Iberdomide compared to 2.3% on placebo.
- Dizziness: 3.1% of patients on Iberdomide compared to 1.3% on placebo.
In a separate study involving patients with hyperphosphatemia undergoing dialysis (NCT04746667), specific side effects were observed. Hyperkalemia (high potassium levels) occurred in 10-20% of patients taking Iberdomide across different doses, compared to 0% on placebo. AV fistula complications were reported in 10% of patients receiving the 0.3 mg and 0.6 mg doses of Iberdomide, with 0% on placebo.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
A Phase 2 clinical trial (NCT04746654) evaluated the effectiveness of Iberdomide 0.1 mg daily in patients with IBS-C over 12 weeks. The primary goal was to measure the overall responder rate, defined as patients experiencing at least a 30% reduction in average weekly abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of the 12 treatment weeks. Results showed that 44% of patients taking Iberdomide were overall responders, compared to 33% of patients on placebo.
Key secondary outcomes also demonstrated improvements:
- Abdominal Pain Relief: 48% of patients on Iberdomide experienced significant abdominal pain relief, compared to 37% on placebo.
- CSBM Responder Rate: 41% of patients on Iberdomide achieved a significant increase in CSBMs, compared to 30% on placebo.
- Stool Consistency: Patients taking Iberdomide experienced a mean improvement of 1.5 points on the Bristol Stool Scale, indicating softer stools, compared to a 0.8-point improvement with placebo.
- Quality of Life: Patients on Iberdomide reported a mean 15-point increase in their IBS-Quality of Life (IBS-QOL) score, suggesting improved well-being, compared to an 8-point increase with placebo.
Hyperphosphatemia in Dialysis Patients
A Phase 2 study (NCT04746667) investigated Iberdomide for reducing high phosphate levels (hyperphosphatemia) in patients undergoing dialysis. The trial included different doses of Iberdomide (0.3 mg, 0.6 mg, 1.0 mg) compared to placebo over 4 weeks. The primary endpoint was the change in serum phosphate from baseline.
Patients treated with Iberdomide showed dose-dependent reductions in serum phosphate levels. The highest dose, Iberdomide 1.0 mg, reduced serum phosphate by an average of 2.5 mg/dL, while the 0.6 mg dose reduced it by 1.8 mg/dL, and the 0.3 mg dose by 1.2 mg/dL. In contrast, patients on placebo experienced only a 0.1 mg/dL reduction.
A significant proportion of patients on Iberdomide achieved the target serum phosphate level of less than 5.5 mg/dL. 70% of patients on the 1.0 mg dose reached this target, compared to 50% on the 0.6 mg dose, 30% on the 0.3 mg dose, and 10% on placebo. Importantly, Iberdomide did not cause significant changes in serum calcium levels.
Currently Recruiting Trials
Iberdomide is currently being investigated in a variety of clinical trials for patients with multiple myeloma and other blood cancers. These studies aim to understand its safety and effectiveness, often in combination with other established or experimental therapies.
- One Phase 1 study, NCT06896916, is assessing the safety and changes in disease activity of etentamig in combination with a cereblon E3 ligase modulatory drug (CELMoD) agent in adult participants with relapsed or refractory multiple myeloma. This trial is recruiting up to 135 participants.
- Another Phase 1 trial, NCT06348108, is evaluating talquetamab in combination with iberdomide and dexamethasone for relapsed or refractory multiple myeloma, with an enrollment target of 32 participants.
- For patients with smouldering myeloma, a Phase 2 study (NCT06762769) is testing isatuximab and iberdomide as immunotherapy for high-risk cases, aiming to enroll 63 participants.
- The Alliance for Clinical Trials in Oncology is sponsoring a Phase 1/2 trial (NCT06232044) combining iberdomide with belantamab mafodotin and dexamethasone for relapsed or refractory multiple myeloma, seeking 88 patients.
- Mayo Clinic is conducting a Phase 1/2 study (NCT06785415) on elotuzumab, daratumumab, iberdomide, and dexamethasone for relapsed multiple myeloma, with an enrollment goal of 37 participants.
- In newly diagnosed, transplant-ineligible multiple myeloma patients, the Canadian Myeloma Research Group is evaluating iberdomide, bortezomib, dexamethasone, and isatuximab in a Phase 2 study (NCT05272826) with 75 participants.
- A large Phase 3 study (NCT05827016) sponsored by Bristol-Myers Squibb is comparing iberdomide maintenance therapy to lenalidomide maintenance after autologous stem cell transplant in newly diagnosed multiple myeloma, targeting 1216 participants.
- Notably, Iberdomide is also being studied beyond multiple myeloma. A Phase 1 study (NCT05169515) by Hoffmann-La Roche is investigating mosunetuzumab or glofitamab in combination with CELMoDs (including CC-220, which is Iberdomide) in participants with B-cell Non-Hodgkin Lymphoma, with an enrollment of 121 individuals.
Where to Participate
Clinical trials for Iberdomide are actively recruiting across a wide geographic area, with 226 study sites located in 137 cities across 36 states in the United States. Many major medical centers are participating, offering opportunities for patients in various regions.
The top cities with the most recruiting sites include:
- New York, New York (10 sites)
- Boston, Massachusetts (9 sites)
- Omaha, Nebraska (6 sites)
- Atlanta, Georgia (6 sites)
- Houston, Texas (6 sites)
- Charlotte, North Carolina (6 sites)
- Seattle, Washington (5 sites)
- Milwaukee, Wisconsin (5 sites)
- Columbus, Ohio (5 sites)
- Rochester, Minnesota (4 sites)
Eligibility for these trials generally requires participants to be between 18 and 75 years of age. All genders are welcome, but these studies are not open to healthy volunteers or children, focusing specifically on patients with the conditions being studied.
Development Timeline
The clinical development journey for Iberdomide began on May 18, 2020, with initial investigations into conditions such as IBS-C and hyperphosphatemia. Over time, the focus significantly expanded, particularly into various forms of multiple myeloma.
Key organizations like Bristol-Myers Squibb and the National Cancer Institute (NCI) have been instrumental in driving Iberdomide's research, alongside many other academic institutions and pharmaceutical companies. The pipeline quickly broadened to include a wide range of multiple myeloma indications, such as recurrent, relapsed, refractory, newly diagnosed, and smouldering multiple myeloma. This expansion reflects a growing understanding of Iberdomide's potential in these challenging blood cancers.
The development program has progressed steadily, with a total of 35 trials conducted to date, involving over 5,185 participants. While many studies are in early phases (Phase 1 and Phase 1/2), a significant number have advanced to later stages, with 12 trials in Phase 2 and 4 trials in Phase 3. This progression indicates a maturing clinical profile for Iberdomide. Beyond multiple myeloma, the drug's potential has also been explored in other areas, including Non-Hodgkin Lymphoma, showcasing its diverse therapeutic promise.