Daratumumab Clinical Trials

What Is Daratumumab?

Daratumumab is an FDA-approved medication for multiple myeloma. It is a monoclonal antibody that targets the CD38 protein, which is found on the surface of multiple myeloma cells and other immune cells. By attaching to CD38, daratumumab helps the immune system identify and destroy these cells. This action makes it a cytolytic antibody, meaning it works by killing cells.

In addition to its approved use, daratumumab is being investigated in clinical trials for other plasma cell disorders and autoimmune conditions. These include plasma cell myeloma, AL amyloidosis, immune thrombocytopenia, systemic lupus erythematosus (SLE), Waldenstrom's macroglobulinemia (WM), and B- or T-cell acute lymphoblastic leukemia (ALL).

Uses and Conditions Under Study

Daratumumab is extensively studied across a broad range of conditions, primarily focusing on cancers involving plasma cells. Clinical trials for daratumumab have enrolled a total of 54,035 participants across 347 trials, with 85 trials currently recruiting and 82 completed. The first trial began in 2007, and the latest is projected to conclude in 2026.

• Multiple Myeloma and Related Conditions: The most significant area of study for daratumumab is multiple myeloma, a cancer of plasma cells found in the bone marrow. It is being investigated for various stages and types of this disease, including newly diagnosed, relapsed, and refractory multiple myeloma, as well as plasma cell myeloma. A total of 167 trials focus on multiple myeloma, with additional trials for related conditions like Plasma Cell Myeloma (14 trials), Recurrent Plasma Cell Myeloma (12 trials), Refractory Multiple Myeloma (11 trials), Refractory Plasma Cell Myeloma (8 trials), Newly Diagnosed Multiple Myeloma (7 trials), and Relapsed/Refractory Multiple Myeloma (6 trials). Daratumumab's ability to target CD38 on these cancerous cells is central to its potential in these treatments.
• AL Amyloidosis: Daratumumab is being studied in 9 trials for AL amyloidosis, a rare disease where abnormal proteins produced by plasma cells accumulate in organs, causing damage. Targeting the plasma cells with daratumumab may help reduce the production of these harmful proteins.
• Immune Thrombocytopenia (ITP): This autoimmune disorder involves the immune system mistakenly destroying platelets, leading to bleeding. Daratumumab is being explored in 7 trials for ITP, likely due to its immunomodulatory effects on CD38-expressing immune cells involved in the disease.
• Other Conditions: Daratumumab is also under investigation for other conditions such as Systemic Lupus Erythematosus (SLE), Waldenstrom's Macroglobulinemia (WM), Autoimmune Hemolytic Anemia (AIHA), and B- or T-cell acute lymphoblastic leukemia (ALL). These studies aim to understand the drug's safety and effectiveness in a wider range of immune-mediated and hematologic disorders.

Dosing

Daratumumab is administered through different routes, primarily as an intravenous (IV) infusion or a subcutaneous (SC) injection. The specific dosage and schedule depend on the condition being treated and whether it is part of a combination therapy.

For subcutaneous administration, a dose of 1800 mg has been studied, often given in the thigh or abdomen. For intravenous administration, doses such as 1.9 mg/kg have been investigated, with schedules varying from weekly to every 8 or 12 weeks. For example, some regimens involve 1.9 mg/kg IV every 8 weeks for the first 24 weeks, followed by every 12 weeks thereafter, until disease progression or unacceptable toxicity. Other IV regimens have included administration once a week for 4 weeks.

Daratumumab is frequently used in combination with other medications, such as lenalidomide, bortezomib, and dexamethasone, in complex treatment plans that may involve induction, consolidation, and maintenance phases. These regimens can extend for fixed durations, such as 24 cycles (approximately two years), or until disease progression.

Side Effects

The provided clinical trial data primarily reports the number of participants who experienced adverse events rather than specific side effect frequencies for Daratumumab. No placebo comparison data for specific side effects was available in the provided information.

In a study (NCT01592370) investigating Daratumumab in combination with Nivolumab for multiple myeloma, drug-related Grade 3-4 adverse events (severe or life-threatening) were observed in various cohorts. The highest number of participants experiencing these events was 13 participants in Cohort B1. Drug-related Grade 3-4 serious adverse events (SAEs) in the same study were most frequently reported in Cohort B1, with 10 participants affected.

Additionally, clinical laboratory abnormalities by worst toxicity grade were noted in the Nivolumab + Daratumumab cohorts. In Cohort B1, 10 participants experienced hematology abnormalities, 9 participants had liver abnormalities, and 8 participants showed thyroid abnormalities.

In another study (NCT00574288) evaluating Daratumumab alone, the number of participants who experienced adverse events varied by dose and study part. In Part 2, 41 participants receiving 16 mg/kg Daratumumab reported adverse events. A study combining Daratumumab with pomalidomide and dexamethasone (NCT01946477) reported that 105 participants in Cohort B (Daratumumab combination) experienced treatment-emergent adverse events.

Clinical Trial Results

Daratumumab Monotherapy in Multiple Myeloma

In a safety study (NCT00574288) of Daratumumab (HuMax®-CD38) in patients with multiple myeloma, various response rates and survival outcomes were observed across different dose levels. In Part 1, the overall response rate (ORR) was highest at the 24 mg/kg dose, with 66.7% of participants responding. For the 16 mg/kg dose, the ORR was 33.3%. In Part 2, the 16 mg/kg dose showed an ORR of 35.7%, while the 8 mg/kg dose had an ORR of 10.0%.

The median time to response in Part 1 was 1.9 months for the 24 mg/kg dose and 8.4 months for the 16 mg/kg dose. For Part 2, the median overall survival for patients receiving 16 mg/kg Daratumumab was 34.3 months, compared to 18.2 months for those on 8 mg/kg. The median progression-free survival in Part 2 was 5.6 months for the 16 mg/kg dose and 2.4 months for the 8 mg/kg dose.

Daratumumab in Combination Therapies for Multiple Myeloma

Studies have also evaluated Daratumumab in combination with other treatments for multiple myeloma. In a trial (NCT01946477) comparing pomalidomide and dexamethasone (Cohort A) with the addition of Daratumumab (Cohort B), significant improvements were seen with the triple combination. The overall response rate was 79.5% for the Daratumumab combination (Cohort B), compared to 32.1% for Cohort A. Median overall survival was also longer in the Daratumumab combination group at 56.7 months, compared to 38.2 months for Cohort A.

Another study (NCT01615029) investigated Daratumumab in combination with lenalidomide and dexamethasone. In Phase 1, the overall response rate for the combined Daratumumab (2-16 mg/kg) regimen was 85.4%. In Phase 2, the 16 mg/kg Daratumumab combination achieved an overall response rate of 81.3%, with a median time to response of 0.99 months.

When Daratumumab was combined with ixazomib citrate and cyclophosphamide (NCT01415882, Arm E), the proportion of confirmed responses was 75.0%, and the median event-free survival was 29.5 months.

A trial exploring Nivolumab and Daratumumab in combination (NCT01592370) showed varying objective response rates across different cohorts. Cohort A-2 had an objective response rate of 71.4%. The median progression-free survival in these cohorts ranged up to 16.95 months (Cohort A-2).

Currently Recruiting Trials

Daratumumab, an anti-CD38 monoclonal antibody, is currently being investigated in 85 recruiting clinical trials across various conditions. These studies aim to evaluate its effectiveness and safety, sometimes alone and often in combination with other treatments. Here are some of the trials actively seeking participants:

• A Phase 2 study (NCT07362199) is assessing Daratumumab combined with Rituximab for adults with primary immune thrombocytopenia (ITP) who have not responded to or have relapsed after previous glucocorticoid treatment. This trial plans to enroll 20 participants.
• Another Phase 2 study (NCT07362238) is comparing Daratumumab to Rituximab in pediatric patients with primary ITP who have also not responded to or relapsed after prior glucocorticoid treatment. This study aims to enroll 122 children.
• For patients with relapsed or refractory multiple myeloma, a Phase 3 study (NCT07452198) is comparing GR1803 Injection against a standard regimen of Daratumumab, Pomalidomide, and Dexamethasone (DPd). This trial is recruiting 358 participants.
• A large Phase 2/3 trial (NCT07095452) is exploring Etentamig plus Daratumumab compared to Daratumumab, Lenalidomide, and Dexamethasone (DRd) in adults with newly diagnosed multiple myeloma who are not eligible for transplant. This study has an enrollment target of 660 participants.
• Researchers are also investigating Daratumumab in combination with teclistamab or talquetamab for frail patients with newly diagnosed multiple myeloma in a Phase 2 study (NCT07107529), with 150 participants planned.
• A Phase 1/2 study (NCT07075510) is examining the safety and tolerability of subcutaneous Daratumumab when administered in the thigh versus the abdomen for patients with plasma cell disorders, involving 30 participants.
• In a Phase 3 trial (NCT06679101), Belantamab Mafodotin combined with Lenalidomide and Dexamethasone (BRd) is being compared to Daratumumab, Lenalidomide, and Dexamethasone (DRd) in 520 participants with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation.
• A Phase 2 study (NCT06142396) is assessing Daratumumab-hyaluronidase (dara SC) with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) in 30 newly diagnosed multiple myeloma patients who also have new onset renal failure.
• For patients with newly diagnosed light-chain amyloidosis and a specific genetic translocation (11;14), a Phase 2 study (NCT06629818) is evaluating Daratumumab combined with Venetoclax and Dexamethasone, aiming for 36 participants.
• A Phase 3 trial (NCT06022939) is comparing Daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-VCD) chemotherapy plus a stem cell transplant versus Dara-VCD alone for 338 patients with newly diagnosed AL amyloidosis.
• Daratumumab is also being studied for non-cancer conditions, such as in a Phase 2 study (NCT06889948) to treat kidney diseases like monoclonal gammopathy of renal significance (MGRS), with 30 participants.
• A large Phase 3 study (NCT05552222) is comparing combinations of teclistamab or talquetamab with Daratumumab and lenalidomide against Daratumumab, lenalidomide, and dexamethasone (DRd) in 1590 participants with newly diagnosed multiple myeloma.

Where to Participate

Clinical trials for Daratumumab are conducted globally, offering opportunities for participation across many regions. For instance, a broad Phase 2 study (NCT03899155) examining various cancer therapies, including Daratumumab combinations, is recruiting in 1335 sites across 666 cities and 50 states.

Top recruiting locations for this extensive study include