Phase 1b trial enrolling to test continuous low-dose lenalidomide

STAR-LLD was developed to provide therapeutic levels via continuous delivery

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by Steve Bryson, PhD |

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The Gabrail Cancer Center (GCC) in Canton, Ohio is the first site to open in a Phase 1b clinical trial that’s evaluating STAR-LLD, Starton Therapeutics’ investigational continuous delivery of low-dose lenalidomide, in people with multiple myeloma.

“I’m thrilled to be the study’s lead investigator and excited about the potential opportunity STAR-LLD can bring multiple myeloma patients,” Nash Gabrail, MD, a medical oncologist and GCC founder, said in a Starton press release.

The U.S.-based trial, which is expected to enroll up to six patients at three or four clinical sites, has begun screening potential participants for eligibility ahead of dosing in the coming weeks.

STAR-LLD, given as an into-the-vein (intravenous) infusion, will be tested with Velcade (bortezomib) and dexamethasone as a second line of therapy for myeloma patients ineligible for a stem cell transplant.

GCC oversaw two expansions due to the increase in the number of trials and the addition of diagnostic imaging services, and now attracts trial participants from around the world, the release stated.

The site’s opening comes several months ahead of schedule, significantly accelerating the clinical trial timeline, according to Starton.

“We are pleased to be working with Dr. Gabrail and his team at Gabrail Cancer & Research Center again,” said Amy Chergey, Stanton’s executive director of clinical operations. “The clinical and nursing staff are truly remarkable professionals who exhibit unwavering dedication to patient care, consistently going above and beyond to ensure the well-being of their patients. Their expertise, commitment and compassion create an environment of trust and healing for patients.”

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Data: Revlimid Triple Combo Is Better as Myeloma Maintenance Therapy

What is STAR-LLD and what does it do?

Lenalidomide is an immunomodulatory therapy that stimulates the immune system to kill cancer cells. It also suppresses new blood vessel formation, thereby reducing tumor growth.

In Europe, a combination of Velcade, dexamethasone, and oral lenalidomide (sold as Revlimid, with generics available) is approved for adults newly diagnosed with multiple myeloma who are ineligible for a transplant.

Sold by Bristol-Myers Squibb’s subsidiary Celgene, Revlimid is a standard oral treatment for myeloma. The oral administration results in fluctuating therapy levels, however, and they reach their maximum soon after dosing and steadily drop until the next dose.

This has resulted in significant dose-dependent side effects, including neutropenia (low immune neutrophils), that limit the therapy’s tolerance, and lower than target levels that may lead to treatment failure.

STAR-LLD was developed to provide therapeutic levels of lenalidomide, but at lower doses administered via continuous delivery, which should reduce its side effects and improve tolerance.

“Quality of life is just as important as life itself,” Gabrail said.

Starton is developing three STAR-LLD delivery systems — a portable under-the-skin infusion pump, a skin patch, and a patch/pump on-body injector.

A study in animal models showed STAR-LLD shrank the tumors caused by human myeloma cells by 80% compared with untreated cells that grew by 25 times. Even with daily abdominal injections of lenalidomide, tumors still grew fivefold.

With continuous delivery of low-dose lenalidomide, all the animals showed tumor shrinkage, and 20% were tumor-free after 100 days versus none given daily lenalidomide injections, according to Starton.

In a previous Phase 1 study, STAR-LLD, administered through the under-the-skin infusion pump, was generally well tolerated in healthy male volunteers, without reports of dose-related toxicity or side effects.

Blood tests revealed that, compared with Revlimid, STAR-LLD had more than 91% of bioavailability, that is, the fraction of it that reached circulation and was distributed to reach its target areas. Moreover, STAR-LLD showed a 90% lower maximum concentration and a 70% lower total exposure relative to Revlimid.

The new Phase 1b trial, recently given the green light by the U.S. Food and Drug Administration, will investigate STAR-LLD’s tolerability and efficacy in myeloma patients who aren’t eligible for stem cell transplant.

Participants will receive 9.6 mg of STAR-LLD a day (400 micrograms per hour), with Velcade and dexamethasone, over 10 months.

Researchers will assess the proportion of patients responding to treatment, response duration, progression-free survival, and minimal residual disease, that is, the number of cancer cells remaining after treatment. Changes in the levels of several immune cells and related signaling proteins will also be measured.