Starton Therapeutics has successfully completed enrollment for its STAR-LLD Phase 1b clinical trial in multiple myeloma, marking a significant milestone in the development of continuous subcutaneous lenalidomide delivery technology. The biotechnology company finished enrollment significantly ahead of its original 10-month timeline, with early safety data suggesting potential advantages over standard oral Revlimid therapy.
Enhanced Safety Profile Emerges
The Phase 1b trial data from the first 50% of patients reveal a markedly improved safety profile compared to oral lenalidomide. Only two drug-related events have been observed to date: one patient experienced an intermittent injection site rash but continued treatment, while a second patient was discontinued due to a Revlimid skin rash. Notably, none of the more serious typical lenalidomide side effects, including neutropenia, gastrointestinal issues, and severe fatigue, have been documented.
This safety advantage is particularly significant given that up to 30% of patients discontinue oral Revlimid and approximately 70% require dose reductions due to adverse effects. The improved tolerability profile suggests STAR-LLD may expand the eligible patient population for lenalidomide therapy.
Dr. Jamie Oliver, Starton's Chief Medical Officer, emphasized the collaborative effort behind the trial's success: "We are profoundly grateful to our esteemed partners at Gabrail Cancer & Research Center and Regional Medical Oncology Center for their remarkable commitment to our clinical trial, tirelessly caring for every patient's needs along the way."
Preclinical Data Demonstrates Superior Efficacy
The continuous delivery approach has shown remarkable results in preclinical studies. In a proof-of-concept study, multiple myeloma tumors caused by human myeloma cells grew 25-fold when untreated and five-fold when treated with daily lenalidomide. In contrast, tumors treated with STAR-LLD shrank by 80% over a single 28-day cycle.
The preclinical data revealed a 100% overall response rate using continuous delivery lenalidomide, with 20% of animals achieving tumor-free status after 100 days. This compared to a 0% overall response rate in animals treated with a 70% higher dose of lenalidomide administered in single daily doses.
Bioavailability and Pharmacokinetic Advantages
A Phase 1 bioavailability study in healthy men demonstrated that STAR-LLD is well tolerated and achieves greater than 91% bioavailability through the subcutaneous route. Importantly, the maximum concentration (Cmax) was less than 90% lower than oral Revlimid, potentially contributing to the improved safety profile while maintaining therapeutic efficacy.
Regulatory Pathway and Future Development
As part of development plans agreed upon with the FDA, Starton will prepare an initial summary of safety and activity data while patients continue treatment for efficacy endpoints. This interim review for the End of Phase 1 meeting, anticipated for Q4 2024, aims to develop plans for the approval pathway forward with Phase 2 studies for multiple myeloma and other malignancies where lenalidomide has demonstrated activity but lacks approval.
Pedro Lichtinger, Chairman and CEO of Starton Therapeutics, stated: "This milestone marks a significant step forward in our commitment to bringing more advanced therapies to patients. With enrollment now complete, we are poised to advance to the next stages of clinical development, furthering our mission to expand and replace lenalidomide in key segments of MM and bring to CLL patients a new mode of action with proven efficacy."
Clinical Trial Design and Patient Population
The STAR-LLD Phase 1b trial assesses the safety, pharmacokinetics, and efficacy of continuous subcutaneous administration of low-dose lenalidomide in combination with dexamethasone and bortezomib (Velcade). The study enrolled patients at two clinical sites: Gabrail Cancer & Research Center and Regional Medical Oncology Center in Wilson, North Carolina.
The company's proprietary transdermal technology is designed to increase the efficacy of approved drugs while improving tolerability and expanding potential therapeutic applications. STAR-LLD represents a novel approach to delivering lenalidomide for both multiple myeloma and chronic lymphocytic leukemia, conditions where the drug has shown activity but faces limitations due to adverse effects with oral administration.
