Approval Probability
TA Base Rate
Adjusted LOA
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Daratumumab · 4 trials · 6 indications
Progression-free survival (PFS) was defined as the time from randomization to the earlier of disease progression or death due to any cause. Participants were evaluated for disease response and progression according to the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) as assessed by an Independent Review Committee (IRC). The duration of PFS was right censored for participants who met any of the following conditions: 1. no baseline/post-baseline disease assessments; 2. started a new anti myeloma therapy before documentation of progressive disease or death; 3. progressive disease or death immediately after more than 70 days without disease assessment visit or; 4. alive without documentation of disease progression before the analysis trigger date (PA DCO); 5. lost to follow-up or withdrawn consent.
Simon's two-stage design will be used. An objective response rate of 40%
MRD will be assessed by the MRD scale ranging from 10 (increased disease detection) to -5 (less to no disease detection) after 8 cycles of therapy.
| Arm | Type | Description |
|---|---|---|
| Kd - Carfilzomib and Dexamethasone | ACTIVE_COMPARATOR | Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. |
| KdD - Carfilzomib, Dexamethasone and Daratumumab | EXPERIMENTAL | Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg was further continued on Cycles 7+: day 1 only. |
| Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone | EXPERIMENTAL | Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. Participants will receive daratumumab, carfilzomib, pomalidomide, and dexamethasone on a 28 day schedule. * Daratumumab will be given according to cycle and dosage determined by protocol. * Carfilzomib will be given at 56 mg/m2 on days 1, 8, 15 (except for C1D1 where it is 20 mg/m2) * Pomalidomide will be given daily on days 1-21. * Dexamethasone will be given weekly, split over two days. |
| Arm A - Bortezomib, Lenalidomide and Dexamethasone (VRD) | EXPERIMENTAL | Participants in this group will receive Bortezomib, Lenalidomide and Dexamethasone on a 21 day treatment cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years. |
| Arm B - Carfilzomib, Lenalidomide and Dexamethasone (KRD) | EXPERIMENTAL | Participants in this group will receive Carfilzomib, Lenalidomide and Dexamethasone on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years. |
| Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd) | EXPERIMENTAL | Participants in this group will receive Carfilzomib, Lenalidomide, Dexamethasone with Daratumumab, Acetaminophen, Diphenhydramine and Montelukast on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years. |
| Treatment Arm (D-KRd) | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Dexamethasone | DRUG | Commercially available oral and IV formulas were obtained by investigative sites. Amgen supplied IV or PO dexa for some countries (Poland, Hungry, Romania, Bulgaria, Korea). Dosage modification rules applied based on participant age (participants \> 75 years were given lower doses), dexa-related toxicities, and discontinuation of carfilzomib. |
| Daratumumab | DRUG | Daratumumab was supplied as a concentrated solution for infusion in single-use vials. |
| Carfilzomib | DRUG | Carfilzomib for infusion was supplied as a lyophilized, sterile product in single-use vials. The lyophilized product was reconstituted with preservative-free sterile water for injection, the reconstituted solution contained carfilzomib 2 mg/mL. IV injections lasted approximately 30 minutes. Dose could be modified based on a \>20% change in body weight or toxicity. |
| Pomalidomide | DRUG | predetermined dose, orally, daily per cycle |
| Bortezomib | DRUG | 1.3 mg/m2 administered Subcutaneous (SC) or intravenous (IV) on days 1, 4, 8 and 11 of a 21 day treatment cycle for participants randomized to Arm A. |
| Lenalidomide | DRUG | 10 or 25 mg/day capsules administered PO. Participants randomized in Arm A: 25 mg/day capsules on Days 1 through 14 of a 21 day cycle.; Participants randomized in Arm B: Cycles 1 through 8 - 25 mg/day capsules on Days 1 through 21 of a 28 day cycle; Participants randomized in Arm C: Cycles 1 - 25 mg/day capsules on Days 2 through 21 of a 28 day cycle; Cycles 2 through 8 - 25 mg/day capsules on Days 1 through 21 of a 28 day cycle; Maintenance Therapy: 10 mg capsules on Days 1 through 21 on a 28 days cycle. |
| Acetaminophen | DRUG | 650 mg administered PO. Participants randomized to Arm C: Cycles 1 through 8 - 650 mg administered on Days 1, 8 and 15. |
| Diphenhydramine | DRUG | 25 mg administered via IV Participants randomized to Arm C: Cycles 1 through 8 - 25 mg administered on Days 1, 8 and 15. |
| Montelukast | DRUG | 10 mg administered PO to participants randomized to Arm C prior to the first 4 doses of Daratumumab. |
| Autologous Stem Cell Transplant (ASCT) | BIOLOGICAL | Participants who are MRD positive at the conclusion of 8 cycles of study treatment, and were able to have their stem cells that were extracted, will receive ASCT from participants' bone marrow samples. |
Inclusion Criteria: * Criteria 1 Relapsed or progressive multiple myeloma after last treatment * Criteria 2 Males or females ≥ 18 years of age * Criteria 3 Measurable disease with at least 1 of the following assessed within 21 days prior to randomization: * IgG multiple myeloma: serum monoclonal pa...
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Daratumumab is an investigational antibody being studied for the treatment of multiple myeloma, including relapsed or refractory multiple myeloma and newly diagnosed multiple myeloma. It is being evaluated in combination with other agents such as carfilzomib, lenalidomide, pomalidomide, and dexamethasone across several clinical trials.
Daratumumab is a monoclonal antibody, classified as a -mab, that targets a protein on myeloma cells. It is being studied in combination regimens for multiple myeloma, with ongoing trials assessing its efficacy in both newly diagnosed and relapsed or refractory settings.
Daratumumab is being developed by Amgen Inc. (NASDAQ: AMGN). The company is conducting multiple clinical trials evaluating the drug in combination with other therapies for patients with multiple myeloma.
Daratumumab is in Phase 2 clinical development for multiple myeloma. While one Phase 3 trial has been completed, the drug remains investigational and is not yet approved. Active Phase 2 trials are ongoing in patients with newly diagnosed and relapsed or refractory multiple myeloma.
Daratumumab is being studied in several trials, including NCT03500445, NCT04176718, and NCT04268498, all Phase 2 studies in multiple myeloma. A completed Phase 3 trial, NCT03158688, evaluated daratumumab with carfilzomib and dexamethasone in relapsed or refractory multiple myeloma.
Daratumumab is a distinct monoclonal antibody being studied in combination with agents like carfilzomib, lenalidomide, pomalidomide, and dexamethasone. It is not the same as those drugs; it is an additional therapy being tested alongside them in multiple myeloma treatment regimens.