Credit: Linda Bartlett
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for elotuzumab, a humanized monoclonal antibody
(mAb).
The designation is for elotuzumab used in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received 1 or more prior therapies.
The FDA’s decision is based on findings from a phase 2 trial in which MM patients received that treatment combination.
According to the FDA, breakthrough designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. For a treatment to receive this designation, there must be preliminary clinical evidence that demonstrates the drug may offer substantial improvement over currently available therapy on at least 1 clinically significant endpoint.
About elotuzumab
Elotuzumab is a humanized IgG1 mAb targeting signaling lymphocyte activation molecule (SLAMF7, also known as CS1), a glycoprotein expressed on myeloma and natural killer cells but not detectable in normal tissue.
Researchers are investigating whether, through both direct activation and engagement of natural killer cells, elotuzumab may selectively target and kill SLAMF7-expressing myeloma cells.
Elotuzumab is under investigation as a monotherapy in smoldering myeloma and in combination with other therapies in first-line and relapsed or refractory MM.
A clinical development program for the mAb is underway, including phase 3 trials in first-line MM (ELOQUENT-1) and relapsed or refractory MM (ELOQUENT-2). The agent is also under investigation in a randomized, phase 2 study of bortezomib and dexamethasone in patients with relapsed or refractory MM.
Elotuzumab is under development by AbbVie and Bristol-Myers Squibb.
Phase 2 trial results
The breakthrough therapy designation for elotuzumab is based on results of a randomized, phase 2 trial presented at the EHA 2013 Annual Congress (abstract 14). Study investigators tested 2 doses of the mAb in combination with lenalidomide and low-dose dexamethasone in patients with previously treated MM.
Patients were randomized 1:1 to receive elotuzumab at 10 mg/kg or 20 mg/kg (intravenous infusion on days 1, 8, 15, and 22 of a 28-day cycle in the first 2 cycles and then days 1 and 15 of subsequent cycles) in combination with oral lenalidomide at 25 mg/day on days 1 to 21 and oral dexamethasone at 40 mg/week. Patients were treated until their disease progressed or they developed unacceptable toxicity.
In the 10 mg/kg arm (n=36), which is the dose used in the ongoing phase 3 trials, the median progression-free survival was 33 months, after a median follow-up of 20.8 months. And the objective response rate was 92%.
In the 20 mg/kg arm (n=37), the median progression-free survival was 18 months, after a median follow-up of 17.1 months. And the objective response rate was 76%.
The safety data were consistent with previously reported results for elotuzumab from this trial. In patients receiving elotuzumab at 10 mg/kg or 20 mg/kg, most treatment-emergent adverse events occurred within 18 months of starting therapy.
The most common grade 3/4 adverse events for the 10 mg/kg and 20 mg/kg arms, respectively, were lymphopenia (26% and 9%), neutropenia (21% and 22%), thrombocytopenia (21% and 17%), anemia (13% and 12%), leukopenia (8% and 7%), hyperglycemia (5% and 12%), pneumonia (8% and 5%), diarrhea (10% and 5%), fatigue (8% and 9%), and hypokalemia (8% and 5%).
Two deaths occurred on study. One patient died of pneumonia, multiple organ failure, and sepsis. The other died of disease progression.
