Promising Results for Elotuzumab Push Monoclonal Antibody Into Phase 3 Trial

Adding the new agent elotuzumab to traditional regimens of lenalidomide and low-dose dexamethasone has been found to produce high response rates in patients with relapsed/refractory multiple myeloma (RRMM).

“Elotuzumab does appear to be adding to existing backbones of agents in a very positive way and it does also appear to be well-tolerated,” Paul G. Richardson, MD, first author of a dose-escalation study evaluating the new agent’s use, told ASH Clinical News.

Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the Signaling Lymphocytic Activation Molecule Family Member 7, or SLAMF7, antigen. The drug works by targeting and killing SLAMF-7-expressing myeloma cells, using direct activation and engagement of natural killer cells.

Early research of elotuzumab has been so encouraging, Dr. Richardson said, that it is the first monoclonal antibody for myeloma treatment that has been moved into phase 3 testing. “Elotuzumab is a really exciting new antibody with great promise.”

Dr. Richardson, the clinical program leader and director of clinical research for the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston, presented final results from a phase 1b/2 multi-center dose-escalation trial of elotuzumab, in combination with lenalidomide and dexamethasone, in RRMM patients.

The phase 2 portion of the trial randomly assigned 73 RRMM patients who had never before been treated with lenalidomide to receive either 10 mg/kg (n=36) or 20 mg/kg (n=37) of elotuzumab. All patients also received lenalidomide and dexamethasone in standard doses.

Patients continued on the drug regimen as long as they were still benefiting from the treatment.  Those in the 10 mg/kg group had a median number of 21 treatment cycles, while the 20 mg/kg arm had a median number of 16 cycles. At data cut-off point, 13 patients in the phase 2 trial (6 in the 10 mg/kg group, 7 in the 20 mg/kg group) were still on treatment; 60 patients had discontinued due to disease progression (57%), adverse events (AEs; 20%), or other reasons (23%).

Overall response rate (ORR) was 84 percent: 92 percent in the 10 mg/kg group and 76 percent in the 20 mg/kg group. In terms of other efficacy endpoints:

  • 14 percent of patients achieved either complete or “stringent” complete response
  • 43 percent had a very good partial response
  • 27 percent had a partial response

Among all patients, median progression-free survival (PFS) was 29 months. Patients in the lower-dose elotuzumab group experienced longer median PFS (32 months vs. 25 months in the 20 mg/kg group).

The amount of time before the disease progressed was longer for those in the 10 mg/kg group: median time to progression was 32.5 months for patients taking 10 mg/kg of elotuzumab, but 25 months for the group taking 20 mg/kg.

The study was not powered to distinguish differences between the treatment arms; however, a trend did seem to emerge, Dr. Richardson noted. “The 10 mg/kg dose of elotuzumab does seem to be doing better from a tolerability viewpoint, and it also seems to be doing better from an efficacy point of view.”


Reference

  • Richardson PG, Jagannath S, Moreau P, et al. “Final results for the 1703 phase 1b/2 study of elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma.” Abstract #302. Presented at the American Society of Hematology Annual Meeting, December 8, 2014.

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