What have Darzalex clinical trials shown?
The safety and efficacy of Darzalex™ (daratumumab, Janssen/Genmab) was demonstrated in two Phase 1/2 clinical trials in heavily-pretreated relapsed and/or refractory myeloma.
The SIRIUS study included 106 patients who had received at least 3 prior therapies, including a proteasome inhibitor and an IMiD, or who were refractory to both a proteasome inhibitor and an IMiD. Patients received intravenous (IV) Darzalex at a dose of 16 mg/kg.
- Patients has received an average of 5 prior lines of therapy.
- The overall response rate was 29.2%, with 2.8% of patients achieving a stringent complete response and 9.4% achieving a very good partial response (VGPR).
- Responses lasted an average of 7.4 months.
- The estimated time that patients lived without disease progression was 3.7 months.
- 65% of patients were alive at 1 year.
- At a subsequent cut-off, overall survival was 17.5 months
- Infusion reactions were seen in 43% of patients and most were mild or moderate in nature.
- The most common side effects included fatigue, anemia, nausea, and low platelet counts.
- The most common severe side effects were low platelet, red blood cell, and neutrophil counts.
The GEN501 study evaluated different doses of Darzalex in patients who had received at least 2 prior therapies. Thirty patients received IV Darzalex at a dose of 8 mg/kg and 42 patients received IV Darzalex at a dose of 16 mg/kg. In patients receiving the 16 mg/kg dose:
- Patients had received an average of 4 prior lines of therapies.
- The overall response rate was 36%, including 1 complete response (CR) and 3 VGPR.
- The estimated time that patients lived without disease progression was 5.6 months.
- 65% of patients who responded to therapy did not have disease progression at 1 year.
- 77% of patients were alive at 1 year.
- Infusion reactions were seen in 71% of patients and most were mild or moderate in nature.
- The most common side effects included fatigue, hay fever, and fever.
- The most common severe side effects were pneumonia and low platelet counts.
The promising results of these studies supported the approval of Darzalex, and Darzalex is listed as one of several preferred regimens for previously treated myeloma in current treatment guidelines.
What other Darzalex combinations have been evaluated?
Darzalex is being evaluated in an ongoing multicenter Phase Ib study (MMY 1001) in combination with various myeloma therapies in newly diagnosed and relapsed and/or refractory myeloma.
- In newly diagnosed patients, preliminary results show that Darzalex in combination frontline regimens such as Velcade® (bortezomib, Takeda)-dex, Velcade-Thalomid® (thalidomide, Celgene)-dex, or Velcade-melphalan-dex was well tolerated with encouraging efficacy.
- In heavily pretreated patients, the combination of Darzalex and Pomalyst-dex resulted in a high 71% overall response rate.
How is Darzalex currently being studied in myeloma?
Darzalex is being evaluated when added to various combination therapies in four Phase 3 studies in the United States.
In relapsed and/or refractory myeloma, Darzalex is being evaluated in two fully-enrolled trials:
- In combination with Revlimid® (lenalidomide, Celgene), and dexamethasone.
- In combination with Velcade® (bortezomib, Takeda Oncology) and dexamethasone.
In newly diagnosed myeloma, Darzalex is being evaluated:
- In combination with Revlimid® (lenalidomide, Celgene), and dexamethasone. LEARN MORE
- In combination with Velcade, melphalan, and prednisone. LEARN MORE
Single-agent Darzalex is also being made available as part of an expanded access program (EAP) study for patients with relapsed and/or refractory myeloma. The Multiple Myeloma Research Consortium (MMRC) is currently collaborating with Janssen on this study, which provides access to Darzalex treatment for patients who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD®, Celgene) or whose disease is refractory to both a PI and an IMiD, and who are not eligible for or who do not have access to enrollment in another Darzalex study. LEARN MORE
Interested in learning more about Darzalex clinical trials? Talk to an MMRF Patient Support Nurse to learn more or use our clinical trials finder: