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Positive Results Reported for Daratumumab in Multiple Myeloma Patients

Monoclonal antibody improves response rate in heavily pretreated subjects

Positive findings have been reported in an early open-label study of daratumumab (Janssen Research & Development), an investigational human anti-CD38 monoclonal antibody, in patients with multiple myeloma who had relapsed after or were refractory to at least two or more prior lines of therapy, including proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), chemotherapy, and autologous stem-cell transplantation.

Daratumumab demonstrated a 36% overall response rate (ORR) in patients treated with a 16-mg/kg dose, with responses improving over time.

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by the excess growth and survival of malignant plasma cells. Patients who are refractory to both PIs and IMiDs have a poor prognosis, with an estimated median overall survival of 9 months.

The GEN501 trial had a two-part design. In part 1, 32 patients were treated with escalating doses of daratumumab, and no maximum tolerated dose was identified. In part 2, 72 patients were enrolled in a dose-expansion cohort and received either 8 mg/kg (30 patients) or 16 mg/kg (42 patients) of daratumumab at various schedules until disease progression or unmanageable toxicity occurred, to optimize the doses identified in part 1. After this study, 16 mg/kg was chosen as the dose to be used in all daratumumab clinical trials.

The patients had a median of four prior lines of therapy, and 79% were refractory to their last therapy, including both lenalidomide and bortezomib (64%). In addition, 76% of patients previously received an autologous stem-cell transplant. The study’s primary endpoint was safety. Secondary endpoints included pharmacokinetics; the objective response according to the International Myeloma Working Group (IMWG) uniform response criteria for myeloma; relative reductions in the levels of M protein and free light chains; the time to disease progression; the duration of response; progression-free survival (PFS); and overall survival.

In the 16-mg/kg cohort, the ORRs were 36% (11 partial responses, two very good partial responses, and two complete responses) and 10% in the 8-mg/kg cohort (three partial responses). Median PFS was 5.6 months, and 65% of the responders remained in remission at 12 months.

Serious adverse events (AEs) occurred in 33% of the 16-mg/kg cohort. Infusion-related reactions (IRRs) were experienced by 71% of patients in both the 8-mg/kg and 16-mg/kg cohorts. Most IRRs occurred during the first infusion. No patients discontinued treatment because of an IRR. The most common AEs in either treatment group included fatigue, allergic rhinitis, and pyrexia. The most frequent hematologic AE was neutropenia, which occurred in 12% the 16-mg/kg cohort.

Source: PipelineReview; August 26, 2015.


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