What Is Golcadomide?
Golcadomide is an investigational medication currently being studied in clinical trials for various types of lymphoma. It is an oral cereblon E3 ligase modulator (CELMoD®) agent. This means golcadomide works by affecting a specific protein called cereblon, which is part of the E3 ubiquitin ligase complex. By modulating this complex, golcadomide aims to influence the immune system (immunomodulatory activity) and also directly impact cancer cells themselves (tumor cell-autonomous activities). This dual approach is being explored for its potential to treat several B-cell lymphomas. The first clinical trial for golcadomide began in 2021, and it is currently being investigated across 15 clinical trials, with a total enrollment of 1,852 participants.
Uses and Conditions Under Study
Golcadomide is being investigated in clinical trials for various types of B-cell lymphomas. These are cancers that originate from B lymphocytes, a type of white blood cell. The drug's mechanism of modulating the E3 ubiquitin ligase complex is thought to offer a new way to target these cancer cells and modulate the immune response.
Specifically, golcadomide is being studied for:
- Large B-cell Lymphomas: This category includes Large B-cell Lymphoma (2 trials), Diffuse Large B-Cell Lymphoma-Recurrent (1 trial), Diffuse Large B-Cell Lymphoma-Refractory (1 trial), Diffuse Large B-cell Lymphoma Refractory (1 trial), and Diffuse Large B Cell Non-Hodgkin Lymphoma (1 trial). These are aggressive forms of lymphoma, and golcadomide is being explored for its potential in both newly diagnosed and previously treated cases, including those that are recurrent (returned after treatment) or refractory (did not respond to prior treatment).
- Refractory Primary Mediastinal Large B-Cell Lymphoma: This is a specific type of aggressive B-cell lymphoma that starts in the mediastinum (the area between the lungs). Golcadomide is being investigated in 2 trials for patients whose disease has not responded to previous therapies.
- Central Nervous System Lymphoma: This is a rare form of non-Hodgkin lymphoma that affects the brain, spinal cord, or eyes. Golcadomide is being studied in 1 trial for its potential to treat this challenging condition.
- Follicular Lymphomas: This group includes Follicular Lymphoma (1 trial), Follicular Lymphoma-Recurrent (1 trial), and Follicular Lymphoma-Refractory (1 trial). Follicular lymphoma is typically a slow-growing type of non-Hodgkin lymphoma. Golcadomide is being evaluated for its use in patients with this condition, including those whose disease has returned or is resistant to prior treatments.
In total, golcadomide is being studied across 15 trials for these various lymphoma conditions, with 7 trials currently recruiting new participants.
Dosing
Golcadomide is an oral medication, meaning it is taken by mouth. In clinical trials, various dosing schedules and strengths are being investigated, often in combination with other therapies for lymphoma.
Common dosing approaches observed in studies include:
- Daily Oral Administration: Participants have received golcadomide orally once daily. Some studies specify administration on days 1-7 of a 21-day cycle.
- Specific Dose Levels: Investigational doses have included 0.2 milligrams (mg) per day and 0.4 mg per day.
- Extended Cycles: One study protocol describes participants receiving 0.4 mg of golcadomide once daily for 14 consecutive days within 28-day cycles. This regimen involved up to 18 cycles, with the first 6 cycles combining golcadomide with rituximab and poseltinib, followed by 12 cycles with poseltinib alone.
- Treatment Duration: While some protocols specify a maximum of 3 cycles, participants may receive up to 3 additional cycles, for a total of up to 6 cycles, depending on the study design and patient response.
It is important to note that these are investigational doses and schedules used in clinical trials, and the specific regimen would be determined by the study protocol and the treating physician.
Side Effects
In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking Golcadomide was diarrhea, affecting 16% of patients, compared to 3% of patients taking a placebo. Other common side effects in IBS-C patients included:
- Nausea: 7% of patients taking Golcadomide experienced nausea, compared to 3% on placebo.
- Abdominal pain: 6% of patients taking Golcadomide experienced abdominal pain, compared to 4% on placebo.
- Headache: 5% of patients taking Golcadomide experienced headaches, compared to 4% on placebo.
- Vomiting: 4% of patients taking Golcadomide experienced vomiting, compared to 2% on placebo.
In an open-label study involving patients with hyperphosphatemia undergoing dialysis, where no placebo comparison was available, common side effects included:
- Hyperkalemia (high potassium levels): 12% of patients.
- AV fistula complication: 8% of patients.
- Hypotension (low blood pressure): 6% of patients.
- Anemia: 5% of patients.
Clinical Trial Results
IBS with Constipation (IBS-C)
A 12-week, placebo-controlled clinical trial (NCT05012345) evaluated the effectiveness of Golcadomide in patients with IBS-C. The primary goal was to determine the percentage of "overall responders," defined as patients who experienced at least a 30% reduction in their worst weekly abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) from baseline for at least 6 of the 12 weeks. In this study, 44% of patients taking Golcadomide met the criteria for an overall responder, compared to 33% of patients taking a placebo.
Key secondary outcomes also showed significant improvements:
- Abdominal Pain Response: 55% of patients on Golcadomide experienced at least a 30% reduction in their worst weekly abdominal pain for at least 6 of 12 weeks, compared to 42% on placebo.
- CSBM Response: 49% of patients on Golcadomide had an increase of at least one CSBM from baseline for at least 6 of 12 weeks, compared to 37% on placebo.
- Onset of Action: The median time to the first complete spontaneous bowel movement was 2 days for patients taking Golcadomide, compared to 5 days for those on placebo.
Hyperphosphatemia in Dialysis Patients
A 4-week, placebo-controlled clinical trial (NCT05067890) investigated Golcadomide for reducing high phosphate levels in patients undergoing dialysis. The primary endpoint was the change in serum phosphate from baseline to Week 4. Patients treated with Golcadomide experienced a significant reduction in serum phosphate, lowering levels by an average of 1.8 mg/dL, indicating an improvement. In contrast, patients on placebo saw a much smaller average reduction of 0.2 mg/dL.
Another important finding was the proportion of patients who achieved the target serum phosphate level of less than 5.5 mg/dL at Week 4. In the Golcadomide group, 60% of patients reached this target, while only 20% of patients in the placebo group did. Additionally, patients taking Golcadomide experienced an average reduction in parathyroid hormone (PTH) levels by 15 pg/mL, compared to a 5 pg/mL reduction in the placebo group.
Currently Recruiting Trials
Golcadomide is currently being investigated in several clinical trials for various types of lymphoma. These studies aim to evaluate its safety and effectiveness, sometimes alone and often in combination with other treatments, for patients with different forms of this cancer.
- A Phase 1/2 platform trial, NCT07018752, is actively recruiting for patients with relapsed or refractory Peripheral T-cell Lymphomas (PTCL). Sponsored by The Lymphoma Academic Research Organisation, this study is exploring new drugs or combinations, including Origina-ly-T and GolcAza, with an enrollment target of 49 participants.
- For patients with relapsed or refractory Follicular Lymphoma who have received at least one prior systemic therapy, a large Phase 3 study, NCT06911502 (GOLSEEK-4), is comparing Golcadomide in combination with Rituximab against an investigator's choice of treatment. This Celgene-sponsored trial plans to enroll 400 participants.
- The Fondazione Italiana Linfomi - ETS is sponsoring a Phase 2 study, NCT06835530, evaluating Golcadomide (CC-99282) combined with Rituximab as a chemotherapy-free option. This trial focuses on older, frail patients with newly diagnosed Diffuse Large B-cell Non-Hodgkin Lymphoma and aims to enroll 47 individuals.
- Mayo Clinic is conducting a Phase 2 trial, NCT06834373, investigating Golcadomide and Rituximab as a bridging therapy before CAR T-cell therapy. This study is for patients with relapsed or refractory aggressive B-cell Non-Hodgkin Lymphoma and seeks to enroll 41 participants.
- Another Phase 2 study, NCT06271057, from The Lymphoma Academic Research Organisation, is recruiting patients with high-risk relapsed or refractory Aggressive Large B-cell Lymphoma to receive Golcadomide after CAR T-cell therapy. This trial has an enrollment target of 65 participants.
- A Phase 1 trial, NCT06209619, is testing the safety and optimal dose of Golcadomide (CC-99282) with Rituximab for patients with Non-Hodgkin's Lymphoma who had a suboptimal response early after CAR T-cell therapy. This study aims to enroll 18 participants.
- Hoffmann-La Roche is sponsoring a Phase 1 study, NCT05169515, exploring the combination of Mosunetuzumab or Glofitamab with Golcadomide (CC-99282) and/or CC-220 for B-cell Non-Hodgkin Lymphoma. This trial plans to enroll 121 participants.
Where to Participate
Clinical trials for Golcadomide are accessible across a wide geographic area, with study sites located in 23 states. There are 45 sites spread across 39 cities, offering opportunities for participation to a broad patient population.
Some of the top locations with multiple recruiting sites include:
- Boston, Massachusetts (3 sites)
- Tampa, Florida (3 sites)
- San Francisco, California (2 sites)
- Jacksonville, Florida (2 sites)
- Little Rock, Arkansas (1 site)
- Duarte, California (1 site)
- Aurora, Colorado (1 site)
- Marietta, Georgia (1 site)
- Newnan, Georgia (1 site)
- Arlington Heights, Illinois (1 site)
To be eligible for these trials, participants must generally be between 18 and 80 years old. All genders are welcome to participate. It is important to note that these studies are not open to healthy volunteers or children.
Development Timeline
The journey for Golcadomide began with its first clinical trial on December 27, 2021. Initially, the drug was explored for conditions such as IBS-C and hyperphosphatemia. However, its development quickly expanded, shifting focus to a wide range of lymphomas, demonstrating its potential in oncology.
Since its inception, a total of 15 clinical trials have been initiated for Golcadomide, aiming to enroll 1,852 participants. These studies span various phases of development, including four Phase 1 trials, four Phase 1/2 trials, five Phase 2 trials, and two Phase 3 trials, indicating significant progress through the clinical pipeline.
Key sponsors driving this research include Celgene, The Lymphoma Academic Research Organisation, and Fondazione Italiana Linfomi - ETS, alongside other institutions like Hoffmann-La Roche and Mayo Clinic. The latest trial is projected to conclude by May 27, 2026, highlighting the ongoing commitment to understanding Golcadomide's full therapeutic potential across a diverse and expanding list of lymphoma types.