Date: 2016-10-06
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 Research & Development, a J&J company (USA - NJ)
Product: daratumumab in combination with lenalidomide 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: multiple myeloma
Therapeutic area: Cancer - Oncology
Country: Australia, Belgium, Canada, Denmark, France, Germany, Greece, Israel, Japan, Republic of Korea, The Netherlands, Poland, Russian Federation, Spain, Sweden, Taiwan, UK, USA
Trial
details: This phase 3 study is comparing the effectiveness of daratumumab when combined with lenalidomide and dexamethasone (DRd) to that of lenalidomide and dexamethasone (Rd), in terms of progression-free survival in participants with relapsed or refractory multiple myeloma. (NCT02076009)
Latest
news: * On October 6, 2016, Genmab announced The New England Journal of Medicine (NEJM)has published data from the Phase III POLLUX (MMY3003) study of daratumumab. The POLLUX data were presented at the 21st Congress of the European Hematology Association (EHA) in June. The Phase III POLLUX study enrolled 569 patients who had relapsed or refractory multiple myeloma. Patients were randomized to receive either daratumumab combined with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid), or lenalidomide and dexamethasone alone. The study met the primary endpoint of improving progression-free survival (PFS) (Hazard Ratio (HR) = 0.37; 95% CI 0.27-0.52; p<0.001) for patients treated with daratumumab versus patients who did not receive daratumumab. Patients who received treatment with daratumumab in combination with lenalidomide and dexamethasone had a 63% reduction in risk of their disease progressing, compared to those who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with lenalidomide and dexamethasone has not been reached, compared to an estimated median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone. The overall response rate was 93% in the group of patients treated with daratumumab versus 76% in the group that did not receive daratumumab. The rates of very good partial response or better (76% vs 44%) and complete response or better (43% vs 19%) were also higher for the group treated with daratumumab. Of patients treated with daratumumab, 22% were minimal residual disease negative, versus 5% in those who did not receive daratumumab; negative minimal residual disease translated into improved outcomes. The most common grade 3 or 4 adverse events in patients treated with daratumumab in combination with lenalidomide and dexamethasone versus those who received only lenalidomide and dexamethasone were neutropenia (51.9% vs 37.0%), thrombocytopenia (12.7% vs 13.5%), and anemia (12.4% vs 19.6%). Daratumumab-associated infusion-related reactions occurred in 48% of patients, were mostly grade 1/2, and occurred predominantly during the first infusion. Overall, the safety profile was consistent with known toxicities of daratumumab monotherapy and combination therapy of lenalidomide and dexamethasone. * On May 18, 2016, Genmab announced that the Phase III POLLUX study (MMY3003) of daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma met the primary endpoint of improving progression free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR) = 0.37 (95% CI 0.27-0.52), p < 0.0001). Patients who received treatment with daratumumab in combination with lenalidomide and dexamethasone had a 63% reduction in risk of their disease progressing, compared to those who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with lenalidomide and dexamethasone has not been reached, compared to an estimated median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone. Janssen Biotech will engage in a dialogue with health authorities about the potential for a regulatory submission for this indication. The trial results are also aimed to be presented at the 21st Congress of the European Hematology Association (EHA) as well as submitted for publication in a peer-reviewed journal.
Data from another Phase III study (CASTOR) of daratumumab combined with subcutaneous bortezomib and dexamethasone compared with bortezomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma was also recently published in the New England Journal of Medicine.
The data from the POLLUX study formed the basis, along with data from the CASTOR study, of two regulatory submissions in August; the supplemental Biologics License Application submitted to the FDA and the submission of the variation to the Marketing Authorization to the European Medicines Agency.
Overall, the safety profile of daratumumab in combination with lenalidomide and dexamethasone was manageable and consistent with the known safety profile of the lenalidomide and dexamethasone combination, with the ongoing Phase II study, GEN503, which evaluated safety and efficacy of daratumumab in combination with lenalidomide and dexamethasone as well as daratumumab monotherapy.
Based on the results at the pre-planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC), it was recommended that the data be unblinded. Patients originally assigned to the lenalidomide plus dexamethasone alone treatment group will be offered the option of receiving daratumumab monotherapy following confirmed disease progression. All patients will continue to be monitored for safety and overall survival. Further analysis of the safety and efficacy data is underway and will be shared with the health authorities.
