Starton Therapeutics Inc revealed that the Independent Data Monitoring Committee has recommended advancement to the third and final dose, where healthy subjects will receive the highest strength of STAR-LLD, a continuous delivery lenalidomide infusion, after reviewing the safety data from the first two cohorts in totality.
The Paramus, New Jersey-based clinical stage biotechnology company said in the ongoing Phase 1 STAR-LLD clinical trial, eight healthy subjects in the first two cohorts received 24 hours of STAR-LLD continuous lenalidomide, and a single oral dose of lenalidomide after a 24-hour washout period.
“The Phase 1 study evaluated STAR-LLD bioavailability, safety, and pharmacokinetics,” Starton chief medical officer Jamie Oliver said in a statement. “Progressing to the final dosing interval marks a major milestone in our development program; this study has established the compatibility and utility of the continuous infusion device with our subcutaneous formulation.”
READ: Starton Therapeutics updates on phase 1 of STAR-LLD lenalidomide clinical program
Oliver noted that lenalidomide has been an effective immunomodulatory drug for years in hematologic malignancies, or cancers that begin in blood-forming tissue such as the bone marrow or in the cells of the immune system. There are three main types of hematologic malignancies — leukemia, lymphoma, and multiple myeloma.
“However adverse events, notably neutropenia, have limited its use in certain patient settings. We believe STAR-LLD may be able to expand the use of lenalidomide, where the oral form is not used today,” Oliver added.
Starton previously announced that the upcoming Phase 1b/2 clinical study in multiple myeloma is on track to begin enrollment in 4Q 2022 at three sites in the European Union.
The company said it plans to submit additional regulatory applications in the US and other countries to accelerate the Phase 1b/2 as part of its development approach for STAR-LLD.
Starton CEO Pedro Lichtinger said: “The planned Phase 1b/2 clinical study is expected to establish efficacy in multiple myeloma; based on the response rates observed in our preclinical studies, we believe STAR-LLD will provide a highly efficacious treatment option in newly diagnosed multiple myeloma.”
Starton is pursuing three delivery systems for STAR-LLD, in addition to the subcutaneous ambulatory infusion under investigation in the ongoing Phase 1 clinical trial, the company also has progressed with its transdermal adhesive patch development and development of a patch/pump on-body injector (OBI).
The Phase 1 clinical trial
The clinical trial is a Phase 1 study to evaluate the 24-hour bioavailability, safety, tolerability, and pharmacokinetics of STAR-LLD in healthy people. The study is an open-label, crossover design used to confirm the plasma concentrations of STAR-LLD versus oral lenalidomide that will be further evaluated in a randomized Phase 1b/2 study in patients with multiple myeloma, said the company.
STAR-LLD uses an ambulatory continuous subcutaneous infusion pump to deliver Starton’s proprietary solubilized lenalidomide in a continuous low dose delivery rather than once-a-day (QD) oral dose. The implication of this “precise control” is the maintenance of adequate and effective drug levels over the entire dosage interval, the company explained.
Starton pointed out that its previous in vivo studies found a 77% reduction in plasma lenalidomide exposure using a continuous subcutaneous infusion, versus pulsatile dosing (rapid and transient release of certain amount of molecules within a short time period) at the daily oral equivalent.
STAR-LLD is a continuous delivery lenalidomide aimed at the most common blood cancers, including multiple myeloma and chronic lymphocytic leukemia. A preclinical proof-of-concept study for STAR-LLD showed that multiple myeloma tumors caused by human myeloma cells grew 25-fold if untreated, five-fold when treated with oral lenalidomide and shrank by 80% with STAR-LLD.
The study also showed 100% effectiveness (overall response rate ORR) at 144 mcg continuous LLD and 20% tumor elimination versus 0% ORR with active control with daily pulsatile once daily dosing.
Starton has completed a pre-IND meeting for STAR-LLD SC and all IND-enabling preclinical and CMC studies. The company expects to reference prior findings of non-clinical safety for key sections of the New Drug Application (NDA) for REVLIMID (lenalidomide).
Contact the author Uttara Choudhury at uttara@proactiveinvestors.com
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