The submission by BMS includes results from the ELOQUENT-2 trial that were recently published in the New England Journal of Medicine.
The FDA has accepted elotuzumab, being developed as Empliciti, for priority review. A monoclonal antibody that stimulates the signaling lymphocyte activation molecule F7 (SLAMF7) cell-surface receptor, the biologics license application for elotuzumab was submitted jointly by Bristol-Myers Squibb and AbbVie for the treatment of multiple myeloma in patients who have received 1 or more prior therapies.
The submission primarily includes results from the ongoing ELOQUENT-2 trial, a phase 3 open-label, multicenter global study that included 646 patients at 168 sites who were randomized to receive elotuzumab in combination with lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group) in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. Primary end points of the trial, results of which were published in the New England Journal of Medicine, were progression-free survival (PFS) and overall response rate (ORR). Secondary end points were overall survival (OS) and severity of pain or interference with daily life.
At a median follow-up of 24.5 months, 35% of patients in the elotuzumab group and 20% in the control group were receiving study treatment. PFS at 1 year was 68% (95% confidence interval [CI], 63 to 73) in the elotuzumab group and 57% (95% CI, 51 to 62) in the control group. Median PFS in the elotuzumab group was 19.4 months (95% CI, 16.6 to 22.2) while in the control group, it was 14.9 months (95% CI, 12.1 to 17.2) with a hazard ratio of 0.70 (95% CI, 0.57 to 0.85; P<.001).
The authors concluded that in patients with relapsed or refractory multiple myeloma, the addition of elotuzumab to lenalidomide and dexamethasone, as compared with lenalidomide and dexamethasone as control therapy, improved PFS and the ORR, showing that direct activation and engagement of the innate immune system to selectively kill myeloma cells can provide clinically meaningful and statistically significant improvements in treatment outcomes. The elotuzumab group presented a 30% reduction in disease progression or death compared with the control group. OS studies ae ongoing.
Results from a phase 2 open-label study, which were presented during the annual meeting of the American Society of Clinical Oncology in May this year, were also a part of the submission to the FDA. The study evaluated the advantage of incorporating the monoclonal antibody, elotuzumab, into a treatment regimen of bortezomib/dexamethasone in relapsed-refractory multiple myeloma (RRMM) patients. Results presented showed that the study met its primary end point of PFS: elotuzumab significantly improved PFS when combined with bortezomib/dexamethasone, and elotuzumab-treated patients had a 28% reduction in their risk of disease progression.
Elotuzumab is simultaneously undergoing accelerated assessment in Europe.
“Bristol-Myers Squibb is delighted by the approach both agencies have taken to review the Empliciti applications as it underscores the unmet medical need in the treatment of multiple myeloma and the role Immuno-Oncology may play,” said Michael Giordano, MD, senior vice president, Head of Oncology Development, Bristol-Myers Squibb in a press release. “The acceptance of our applications by the FDA and EMA brings Bristol-Myers Squibb’s Immuno-Oncology science a step closer to helping patients with hematologic malignancies.”