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Daratumumab · 4 trials · 4 indications
To compare the efficacy of iberdomide (also known as BMS-986382), daratumumab, and dexamethasone (IberDd) to that of daratumumab, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (RRMM) in terms of progression free survival (PFS).
To compare the efficacy of iberdomide (also known as BMS-986382), daratumumab, and dexamethasone (IberDd) to that of daratumumab, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (RRMM) in terms of minimal residual disease (MRD) negative complete response (CR) at any time.
Evaluation of response by ORR by irRECIST criteria. Response classification will follow the irRECIST criteria and will be defined as PR or CR. Patients who are lost to follow-up without a valid response assessment will be classified as NR (non-responder, progression). The ORR will be computed for all patients with at least one cycle of the study drug.
Objective response is defined as a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the investigator assessment: sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
Proportion of subjects who have not met a subject stopping rule, and remain free of all of the following through 26 weeks after starting treatment or until receiving a transplant, whichever occurs earlier: 1. Grade 3 or higher infusion reaction 2. Grade 3 or higher infections 3. Any malignancy The study site will grade the severity of adverse events experienced by the study subjects according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (Published November 27, 2017).
Proportion of subjects who meet any one of the following compared to Baseline (Visit 0): 1. Elimination of one human leukocyte antigen (HLA) antibody at Visit 12 (16 weeks ±7 days after starting treatment); 2. 50% or greater reduction in the mean fluorescence intensity (MFI) of at least three HLA antibodies at Visit 12 (16 weeks ±7 days after starting treatment); and/or 3. Kidney transplant with a previously incompatible donor within 26 weeks after starting treatment without graft loss due to acute antibody mediated rejection occurring within the first four weeks post-transplant and caused by an anamnestic response.
Proportion of subjects who meet any one of the following compared to Baseline (Visit 0): 1. Elimination of one human leukocyte antigen (HLA) antibody at Visit 14 (26 weeks ±7 days after starting treatment); 2. 50% or greater reduction in the mean fluorescence intensity (MFI) of at least three HLA antibodies at Visit 14 (26 weeks ±7 days after starting treatment); and/or 3. Kidney transplant with a previously incompatible donor within 52 weeks after starting treatment without graft loss due to acute antibody mediated rejection occurring within the first four weeks post-transplant and caused by an anamnestic response.
| Arm | Type | Description |
|---|---|---|
| Daratumumab in combination with Iberdomide and dexamethasone - Dose 1 | EXPERIMENTAL | Participants will receive oral iberdomide, subcutaneous daratumumab and oral dexamethasone. |
| Daratumumab in combination with Iberdomide and dexamethasone - Dose 2 | EXPERIMENTAL | - |
| Daratumumab in combination with Iberdomide and dexamethasone - Dose 3 | EXPERIMENTAL | - |
| Daratumumab in combination with dexamethasone and bortezomib | ACTIVE_COMPARATOR | Participants will receive subcutaneous daratumumab, bortezomib and oral dexamethasone |
| Pancreatic Ductal Adenocarcinoma | EXPERIMENTAL | - |
| Refractory Non-Small Cell Lung Cancer | EXPERIMENTAL | - |
| Administration of Daratumumab (DARA) plus Durvalumab (DURVA) | EXPERIMENTAL | Subjects will also receive IV DURVA at 1500 mg on Day 2 (Cycle 1) and on Day 1 (Cycles ≥ 2) of each 28-day treatment cycle. Subjects will receive intravenous (IV) DARA at 16 mg/kg on the same dosing schedule (weekly \[QW\], every 2 weeks \[Q2W\], or every 4 weeks \[Q4W\] of each 28-day treatment cycle) received during their last prior therapy containing DARA at the time of DARA progression |
| Cohort 1 (N=5 Subjects) | EXPERIMENTAL | Multiple intravenous infusions of daratumumab and belatacept over 10 weeks: * Daratumumab will be administered intravenously at a dose of 8 mg/kg weekly for 4 weeks, then every other week for 4 weeks (week 9 and week 11). The dose administered will be calculated based on the actual body weight of the subject at each visit. * Belatacept will be administered intravenously at a dose of 10 mg/kg every 2 weeks starting at week 8 (dosed at weeks 8, 10, 12, and 14). The total infusion dose of belatacept will be based on the actual body weight of the subject at the baseline visit, and will not be modified during the course of therapy, unless there is a change in body weight of greater than 10%. |
| Cohort 2 (N=10 Subjects) | EXPERIMENTAL | The enrollment of ten additional subjects is dependent on the results in Cohort 1. Multiple intravenous infusions of daratumumab and belatacept over 14 weeks:° * Daratumumab will be administered intravenously at a dose of 8 mg/kg for the first dose, then 16 mg/kg for subsequent given weekly for 3 weeks, then every 2 weeks for 2 doses (week 9 and week 11). The dose administered will be calculated based on the actual body weight of the subject at each visit. * Belatacept will be administered intravenously at a dose of 10 mg/kg every 2 weeks starting at week 8 (dosed at weeks 8, 10, 12, 14, 16 and 18). The total infusion dose of belatacept will be based on the actual body weight of the subject at the baseline visit and will not be modified during the course of therapy, unless there is a change in body weight of greater than 10%. * Was modified based on the safety and efficacy analysis of Cohort 1. |
| Name | Type | Description |
|---|---|---|
| Dexamethasone | DRUG | Oral dexamethasone 40mg on days 1, 8, 15, 22 of a 28-day cycle |
| Daratumumab | DRUG | Subcutaneous Daratumumab 1800mg on Days 1, 8, 15 and 22 for Cycles 1 to 2, on Days 1 and 15 for Cycles 3 to 6, and then on Day 1 for Cycle 7+ of a 28-day cycle |
| Bortezomib | DRUG | Subcutaneous Bortezomib 1.3 mg/m2 on Days 1, 4, 8 and 11 of each 21-day cycle for a total of 8 cycles. |
| Iberdomide | DRUG | Oral Iberdomide 1.0mg on Days 1 to 21 of a 28-day cycle |
| KRAS vaccine | BIOLOGICAL | Stimulon QS-21 and Targovax TG01 |
| Nivolumab | DRUG | anti-PD-1 (programmed cell death protein 1) monoclonal antibody (mAb) |
| DURVALUMAB | DRUG | DURVALUMAB |
| belatacept | BIOLOGICAL | Belatacept, a monoclonal antibody, is indicated for the prophylaxis of organ rejection in adult patients receiving a kidney transplant. In this study, belatacept will be used in subjects who have not received a kidney transplant. |
| Bone marrow aspiration | PROCEDURE | Subjects will undergo a bone marrow aspiration prior to starting the study regimen and at 12 weeks after starting the study regimen. In subjects who undergo a kidney transplant during the study, another bone marrow aspiration will be done if it has been \>4 weeks since the previous bone marrow aspiration. |
Inclusion Criteria * Documented diagnosis of multiple myeloma (MM) and measurable disease. * Received 1 to 2 prior lines of anti-myeloma therapy. * Must have documented disease progression during or after their last anti-myeloma regimen. * Eastern Cooperative Oncology Group (ECOG) performance statu...
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Daratumumab is an investigational anti-CD38 antibody being studied for multiple myeloma, pancreatic ductal adenocarcinoma, and highly sensitized prospective kidney transplant recipients. It is in Phase 3 clinical development for relapsed or refractory multiple myeloma. Daratumumab is not FDA approved for these indications and remains under clinical investigation.
Daratumumab targets CD38, a cell surface protein. It is a monoclonal antibody, classified as a -mab (antibody) modality. By binding to CD38, it is designed to interfere with cells expressing this protein, which is relevant in the conditions under study.
Daratumumab is developed by Bristol-Myers Squibb Company, traded as BMY on the stock exchange. The company is conducting clinical trials to evaluate the drug's safety and efficacy across multiple indications, including multiple myeloma and other conditions.
Daratumumab is in Phase 3 clinical development. One active Phase 3 trial, NCT04975997, is comparing daratumumab combinations in relapsed or refractory multiple myeloma. Other trials are in Phase 1 and Phase 2. Daratumumab is investigational and not yet approved.
Daratumumab is being studied in several trials. NCT04975997 is a Phase 3 study in multiple myeloma. NCT03000452 is a completed Phase 2 trial in multiple myeloma. NCT04827979 is a completed Phase 1 trial in kidney transplant recipients. NCT06015724 is a recruiting Phase 2 trial in pancreatic cancer and lung cancer.
Yes, Daratumumab is also known as Daratumumab/rHuPH20 Co-formulation. This alternative name refers to a co-formulation that includes rHuPH20. Both names refer to the same drug product being developed by Bristol-Myers Squibb.