The ongoing Phase I/II study of elotuzumab plus lenalidomide and low-dose dexamethasone evaluated multiple doses of elotuzumab in patients with multiple myeloma. The interim results given as an oral presentation today showed that of the 28 treated patients in the trial, 23 (82 percent) had an objective response (OR) by International Myeloma Working Group (IMWG) criteria. A subset analysis showed that of 22 patients who had not previously received lenalidomide treatment, 21 patients (95 percent) achieved an OR.
No dose-limiting toxicities (DLT) were reported in the study up to the highest dose level of 20 mg/kg and a maximum-tolerated dose (MTD) was not established. Two patients experienced serious adverse events of allergic reactions that were related to elotuzumab and were withdrawn from the study. These adverse events resolved with treatment. In addition, other adverse events reported for the combination of lenalidomide, dexamethasone and elotuzumab, regardless of causality to disease or study drugs, included fatigue, diarrhea, constipation, myelosupression, nausea, muscle spasms, fever, chills and dyspnea. Enrollment for the Phase I portion of the study is completed.
"The preliminary data presented today show that elotuzumab in combination with lenalidomide and dexamethasone may have potential as a treatment option for patients with multiple myeloma," said Faheem Hasnain, president and chief executive officer of Facet Biotech. "We are working closely with our partners at Bristol-Myers Squibb to finalize next steps for the elotuzumab development program, and anticipate initiating a global Phase II study in the first half of 2010."
"We, along with our partner, Facet Biotech, are focusing on the investigation of combinations of potential treatments in the hopes of identifying a more efficacious and tolerable option for patients to help them when faced with this serious disease," said Brian Daniels, M.D., senior vice president, Global Development & Medical Affairs, Bristol-Myers Squibb.
"These interim results are of significant scientific and clinical interest. I am very encouraged by the efficacy and safety data seen to date for this combination, which may offer a future treatment option for multiple myeloma patients," said Sagar Lonial, M.D., of the Winship Cancer Institute at Emory University in Atlanta. "Given that elotuzumab, a humanized antibody, has a novel mechanism of action that appears to work synergistically with lenalidomide, we look forward to advancing clinical studies with this antibody to determine its full potential, with the goal of ultimately improving outcomes for myeloma patients."
The primary objective of the Phase I/II study is to evaluate the maximum tolerated dose (MTD) of elotuzumab in combination with lenalidomide and low dose dexamethasone in patients with relapsed MM. The study is also evaluating safety, pharmacokinetics (PK) and clinical response. Elotuzumab in three escalating dose cohorts (5, 10 and 20 mg/kg) is administered by IV infusion.
Interim results from another Phase I/II study were also presented today at the ASH annual meeting. In a study of elotuzumab plus bortezomib in 20 evaluable patients, eight patients, 40 percent, had an OR and 60 percent achieved a clinical response, defined as minimal response or better using the combined European Group for Blood and Marrow Transplant (EBMT) and IMWG criteria. No DLTs were reported and an MTD was not established. The study continues to enroll patients at the 20 mg/kg dose level.
Elotuzumab is a humanized monoclonal antibody directed against CS1, a cell-surface glycoprotein that is highly and uniformly expressed on multiple myeloma cells but is minimally expressed on normal cells. In nonclinical studies, elotuzumab has been shown to induce antibody-dependent cellular cytotoxicity (ADCC) against primary myeloma cells and is currently in Phase I/II clinical development.
About Facet Biotech
Facet Biotech is a biotechnology company dedicated to advancing its pipeline of five clinical-stage products, leveraging its research and development capabilities to identify and develop new oncology drugs and applying its proprietary next-generation protein engineering technologies to potentially improve the clinical performance of protein therapeutics.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company committed to discovering, developing and delivering innovative medicines that help patients prevail over serious diseases. For more information, please visit www.bms.com.