STAR-LLD combo showing potential for multiple myeloma in clinical trial

Phase 1b study of low-dose lenalidomide infusion in hard-to-treat patients

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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STAR-LLD, a continuous infusion of low-dose lenalidomide into the blood, shows the potential to be a better treatment choice than Revlimid, an oral formulation of lenalidomide, for certain people with multiple myeloma, its developer, Starton Therapeutics, reports.

The company’s announcement was based on early data from a Phase 1b clinical trial (NCT06087653) evaluating STAR-LLD in combination with Velcade (bortezomib) and dexamethasone in treating patients ineligible for a stem cell transplant.

With half of its expected six adult patients enrolled — all with measurable disease after at least one line of therapy — the study is assessing the safety, pharmacokinetics, and efficacy of STAR-LLD. Pharmacokinetics refers to a medicine’s movement into, through, and out of the body.

Complete enrollment is expected later this year, and all patients need to administer STAR-LLD at the home using a portable infusion pump, placed under the skin for continuous delivery into the bloodstream. STAR-LLD is being infused at a daily dose of 9.6 mg (400 micrograms per hour) for about one year.

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“While the patient number is small, we believe we may be seeing an improved signal of safety and activity when compared to daily oral doses of lenalidomide [Revlimid],” Jamie Oliver, chief medical officer at Starton, said in a company press release.

Revlimid, taken once a day, is a standard myeloma treatment sold by Celgene, a subsidiary of Bristol-Myers Squibb. Its active component, lenalidomide, activates the immune system to kill cancer cells. It also halts the formation of new blood vessels in the tumor’s vicinity, reducing tumor growth.

While oral administration is easier on patients, therapy concentration drops steadily shortly after the pill is taken. According to Starton, up to 30% of patients on Revlimid discontinue the treatment, and about 70% reduce its dose due to adverse events.

STAR-LLD was developed to provide sustained therapeutic levels of lenalidomide, and fewer side effects.

Adverse events in enrolled patients linked to a prior treatment regimen with Revlimid included nausea, vomiting, deep vein thrombosis (the formation of blood clots, usually in the legs), upper respiratory tract infections, anemia, and fatigue.

None of Revlimid’s more frequent side effects have been reported to date with STAR-LLD, Starton stated, with only mild blood-related toxicities observed after up to three treatment cycles — each cycle lasts 28 days. Additionally, a mild skin reaction in the injection site was reported after four treatment cycles, which resolved after two weeks.

“This new and innovative method of administration of lenalidomide appears to improve safety and tolerability, thus providing patients with another opportunity to reutilize the drug in a safe and potentially more effective manner,” said Mohamad Hussein, MD, an expert in treating multiple myeloma and a member of Starton’s board of directors.

Data from the first two patients show that the levels of M-protein, a biomarker of the disease, fell by at least 50% following the first treatment cycle with STAR-LLD.

Levels of a particular immune cell type with the ability to destroy cancer cells — called interferon gamma producing CD8 T-cells — also increased up to 50% compared with the study’s start (baseline), without signs of overly active innate immune responses.

No signs of T-cells exhaustion, which renders them less capable of fighting cancer, were observed with STAR-LLD.

“The lack of meaningful hematologic [blood-related] toxicity and drug-related adverse events reflects the preclinical data,” Oliver said. “We were happy to see the steady state blood concentrations of lenalidomide achieved the desired target blood levels projected for immune activation.”