Starton Therapeutics Initiates Phase 2a Trial of STAR-LLD for Relapsed/Refractory Multiple Myeloma
核心洞察
Starton Therapeutics (搜索) has dosed the first patient in a Phase 2a randomized trial evaluating STAR-LLD, a continuous subcutaneous delivery formulation of lenalidomide, for relapsed/refractory multiple myeloma treatment.
The study will compare three doses of continuous STAR-LLD infusion against standard oral lenalidomide (Revlimid®) in 24 transplant-ineligible patients, with potential expansion to 69 patients based on tolerability and response rates.
Previous Phase 1b results showed 100% objective response rate in six patients with no grade >2 hematologic toxicity, while preclinical studies demonstrated 80% tumor shrinkage with STAR-LLD versus five-fold growth with daily lenalidomide.
Starton Therapeutics (搜索) has announced the dosing of the first patient in its Phase 2a clinical trial evaluating STAR-LLD, a novel continuous delivery formulation of lenalidomide, for the treatment of relapsed/refractory multiple myeloma (RRMM). The milestone marks a significant advancement in the company's efforts to improve upon standard-of-care therapies through proprietary continuous delivery technology.
Study Design and Patient Population
The Phase 2a trial is designed as a randomized dose-escalation study that will assess the tolerability and efficacy of low-dose lenalidomide in heavily treated multiple myeloma patients. The protocol compares three doses of continuous subcutaneous infusion with STAR-LLD, combined with dexamethasone and a proteasome inhibitor, against oral lenalidomide (Revlimid®) with the same combination therapy.
The study will initially enroll 24 transplant-ineligible patients in second or greater line of therapy, with the option to expand enrollment to a total of 69 patients based on the tolerability of the selected dose and response rate. Enrollment completion is estimated for the first half of 2027.
Promising Early Clinical Data
The Phase 2a trial builds upon encouraging results from a Phase 1b clinical study involving six relapsed/refractory multiple myeloma patients. All patients who received STAR-LLD achieved an objective response, including one complete response and five partial responses. Notably, no patients experienced drug-related anemia, neutropenia, leukopenia, or thrombocytopenia greater than grade 2 in up to 12 cycles of therapy.
"STAR-LLD is designed to improve tolerability while maintaining meaningful minimum effective dose delivery of lenalidomide, which we believe will mitigate the toxic effects of the therapy compared to oral lenalidomide," said Jamie Oliver, PharmD., Chief Medical Officer at Starton Therapeutics (搜索).
Preclinical Proof-of-Concept Results
Preclinical studies have demonstrated the potential superiority of continuous delivery over traditional dosing approaches. In a proof-of-concept study using subcutaneous STAR-LLD, multiple myeloma tumors caused by human myeloma cells grew 25-fold if untreated and five-fold when treated with daily lenalidomide. In contrast, tumors shrank by 80% with STAR-LLD over a single 28-day cycle.
The preclinical study also showed a 100% overall response rate using continuous delivery lenalidomide, with 20% of animals in this cohort remaining tumor-free after 100 days. This compared favorably to a 0% overall response rate in animals treated with a 70% higher dose of lenalidomide given in single daily doses.
Expanded Site Network
Through the Sargon Site Network, the Phase 2 study has expanded from two to six investigational sites across the United States. The newly activated sites are led by distinguished principal investigators including Dr. Steven Bettag in Sheboygan, Wisconsin; Dr. Sumit Sawhney in Coral Springs, Florida; Dr. Ghassan Al-Jazayrly in Los Angeles, California; and Dr. Hamdy Mohtaseb in Bullhead City, Arizona. The original sites are led by Dr. Nash Gabrail in Canton, Ohio, and Dr. Keith Lerro in Wilson, North Carolina.
Dr. Nash Gabrail, the lead investigator, noted, "We are excited to expand the use of STAR-LLD in relapsed and refractory multiple myeloma. Our experience with the Phase 1b study demonstrated positive responses and no meaningful hematologic toxicity, which had a notable impact on the patients' experience."
Technology Platform and Future Applications
STAR-LLD represents Starton's proprietary continuous delivery technology platform, which is designed to increase the efficacy of approved drugs while making them more tolerable and expanding their potential use. The technology seeks to expand and replace the standard-of-care for multiple myeloma and chronic lymphocytic leukemia, two of the most common blood cancers.
Pedro Lichtinger, Chairman and Chief Executive Officer of Starton, emphasized the significance of this milestone: "Dosing the first patient in our Phase 2 study of STAR-LLD marks an important milestone in our mission to redefine the standard of care in multiple myeloma with our proprietary lenalidomide formulation technology. We expect to deliver clinical results that demonstrate improved tolerability and efficacy over current oral dosing, with the ultimate goal of improving patient outcomes."