A newly authorized phase 1b study will evaluate the safety and efficacy of the continuous delivery of lenalidomide among patients with multiple myeloma.
The FDA has agreed that a planned phase 1b study in second-line transplant-ineligible patients with multiple myeloma may proceed. The study is evaluating the combination of bortezomib (Velcade), dexamethasone, and STAR-LLD as a replacement for oral lenalidomide (Revlimid).1
As part of the development plans, a meeting to review the initial data on safety and activity from the study as an interim analysis has been agreed upon by the FDA. At this time, patients are continuing treatment to evaluate the efficacy end points of the study.
The hope for this interim review is to help develop plans for the approval pathway with phase 2 studies for the treatment of patients with multiple myeloma and other malignancies where lenalidomide has shown activity but is not approved.
“Today’s announcement marks a significant development for Starton and patients in need of approved drugs and an improved quality of life, and we are excited to begin this critical program in transplant-ineligible patients with multiple myeloma. This study will provide initial evidence of the impact of continuous delivery of lenalidomide both in terms of safety and efficacy, as well as provide clarity for signals of improvement in patients outcomes,” said Pedro Lichtinger, chairman and chief executive officer of Starton Therapeutics, Inc, in the press release.
STAR-LLD is a continuous delivery lenalidomide currently being developed to expand and replace the standard of care for blood cancers, including multiple myeloma and chronic lymphocytic leukemia. According to preclinical data, STAR-LLD demonstrated that patients with multiple myeloma caused by human myeloma cells grew 25-fold if untreated, 5-fold when treated with daily lenalidomide, and shrank by 80% with STAR-LLD. In the study, the overall response rate (ORR) was 100% at 144 mcg/day continuous LLD and 20% tumor elimination vs 0% ORR with active control with daily pulsatile once daily dosing.2
Additional phase 1 data have shown that in healthy men STAR-LLD was well-tolerated and is >93% bioavailable by the subcutaneous route compared with lenalidomide.1 These data support the safety of the planned phase 1 dose of 400 mcg/hr (9.6 mg a day) vs a standard 25 mg a day dose of lenalidomide.
In this study, 6 patients across 3-4 centers in the United States will be accrued over a period of 10 months and then evaluated. Patients will be assessed for tolerability, immune biomarkers, and signals of efficacy of continuously delivered lenalidomide at the highest planned daily dose.
The study will provide readouts on the tolerability of the regimen and the impact of continuous delivery on immune function by measuring biomarkers of T-cell, NK-cell, and B-cell upregulation, as wells as observing cytokine production induced by lenalidomide. Signals of efficacy will also be provided through assessing response rates, duration of response, progression-free survival, and changes in minimal residual disease.
“We are very happy with the agreed protocol, which allows a quick read for the key safety and efficacy data which we will review with the FDA. The upcoming phase 1b clinical study in multiple myeloma is on track to begin enrollment in Q4 2023. Treatment of second-line patients at our proposed optimal dose of continuous lenalidomide in combination with the proteasome inhibitor [bortezomib] and dexamethasone allows us to demonstrate activity in an established standard of care regimen by replacing [lenalidomide] with STAR-LLD,” concluded Jamie Oliver, chief medical officer of Starton, in the press release.