Date: 2016-08-25
Type of information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in The New English Journal of Medicine
Company: Janssen Biotech - J&J (USA) Genmab (Denmark)
Product: daratumumab combined with bortezomib and dexamethasone
Action
mechanism: monoclonal antibody. Daratumumab is a human CD38 monoclonal antibody with broad-spectrum killing activity. Daratumumab is in clinical development for multiple myeloma. Daratumumab targets the CD38 molecule which is highly expressed on the surface of multiple myeloma cells. Daratumumab may also have potential in other cancers on which CD38 is expressed, including diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, acute myeloid leukemia, follicular lymphoma and mantle cell lymphoma. Daratumumab has been granted Breakthrough Therapy Designation from the FDA for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop and commercialize daratumumab.
Disease: relapsed or refractory multiple myeloma
Therapeutic area: Cancer - Oncology
Country: Australia, Brazil, Czech Republic, Germany, Hungary, Republic of Korea, Mexico, The Netherlands, Poland, Russian Federation, Spain, Sweden, Turkey, Ukraine, USA
Trial
details: The purpose of this study is to assess the effects of administration of daratumumab when combined with Velcade® (bortezomib) and dexamethasone compared with bortezomib and dexamethasone alone, for participants with relapsed or refractory multiple myeloma. This Phase III study has included approximately 490 patients. The primary endpoint of the study is progression free survival (PFS). ( NCT02136134)
Latest
news: * On August 25, 2016, Genmab announced The New England Journal of Medicine has published data from the Phase III CASTOR (MMY3004) study of daratumumab. The CASTOR data were presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting and the 21st Congress of the European Hematology Association (EHA). The Phase III CASTOR study included 498 patients who had relapsed or refractory multiple myeloma. Patients were randomized to receive either daratumumab combined with subcutaneous bortezomib (a type of chemotherapy, called a proteasome inhibitor) and dexamethasone (a corticosteroid), or bortezomib and dexamethasone alone. The study met the primary endpoint of improving progression free survival (PFS); Hazard Ratio (HR) = 0.39, p<0.001. The median PFS for patients treated with daratumumab has not been reached, compared to median PFS of 7.2 months for patients who did not receive daratumumab. The overall response rate was 82.9% for patients treated with daratumumab versus an overall response rate of 63.2% in the group that did not receive daratumumab. The rate of very good partial response or better was also higher for the group treated with daratumumab (59.2% vs 29.1%). The most common grade 3 or 4 adverse events in patients treated with daratumumab in combination with bortezomib and dexamethasone compared to those who only received bortezomib and dexamethasone were thrombocytopenia (45.3% vs 32.9%), anemia (14.4% vs 16.0%) and neutropenia (12.8% vs 4.2%). Daratumumab-associated infusion-related reactions were reported in 45.3% of patients, were mostly grade 1/2, and occurred predominantly during the first infusion. This is consistent with the reported safety profile of daratumumab monotherapy and background bortezomib/dexamethasone therapy. * On April 20, 2016, Genmab announced that two daratumumab abstracts have been accepted for presentation at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, June 3 — 7. The company will present daratumumab Phase III Castor study data, in the Plenary Session at the ASCO meeting on June 5.
Data from the Phase III CASTOR study of daratumumab formed part of the basis of the recent submission of the supplemental Biologics License Application to the FDA and the submission of the variation to the Marketing Authorization to the European Medicines Agency.
Daratumumab Phase III Castor Study Data:
A total of 498 patients with relapsed or refractory multiple myeloma were enrolled in the study. The study met the primary endpoint of improving progression free survival (PFS); Hazard Ratio (HR) = 0.39, pAs announced on March 30, 2016 an Independent Data Monitoring Committee recommended stopping the study as the primary endpoint had been reached at the time of the pre-specified interim analysis. Patients originally assigned to the bortezomib plus dexamethasone treatment group will be offered the option of receiving daratumumab following confirmed disease progression. Patients continue to be monitored for safety and overall survival.
Abstract details: Phase 3 randomized controlled study of daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): CASTOR study— Abstract # LBA4, Oral presentation, Sunday, June 5 at 3:10PM-3:25PM CDT
* On March 30, 2016, Genmab announced that the Phase 3 Castor study (MMY3004) of daratumumab in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma met the primary endpoint of improving progression free survival (PFS) in an interim analysis (p =< 0.0001). The planned interim analysis was conducted by an Independent Data Monitoring Committee (IDMC). Daratumumab showed a tolerable safety profile in the interim analysis. Based on the IDMC's recommendation, the study will be stopped early. Patients originally assigned to the bortezomib plus dexamethasone treatment group will be offered the option of receiving daratumumab following confirmed disease progression. Patients will continue to be monitored for safety and overall survival. Further analysis of the safety and efficacy data is underway. Based on the interim data, Janssen Biotech, who licensed daratumumab from Genmab in 2012, will engage in a dialogue with health authorities about the potential for these data to serve as the basis for a regulatory submission for daratumumab in this indication. These results are planned to be submitted for presentation at an upcoming medical congress, as well as for publication in a peer-reviewed journal. A full study report is being prepared for submission and will be shared with health authorities. Janssen will initiate discussions about the potential for a regulatory submission for this indication.
* On May 1, 2014, Genmab announced that its partner, Janssen Biotech will start a Phase III study of daratumumab in relapsed or refractory multiple myeloma. The study will compare daratumumab in combination with bortezomib and dexamethasone to bortezomib and dexamethasone alone.
