Starton Therapeutics’ STAR-LLD Continuous Delivery Shows Superior Tumor Reduction & Progression Free Survival Compared to Pulsatile Lenalidomide Treatment in Lenalidomide-Resistant Model

Starton Therapeutics Inc. recently announced results from a 28-day efficacy study of STAR-LLD continuous subcutaneous (SC) infusion versus intraperitoneal (IP) lenalidomide in immunomodulatory drug (IMiD)-resistant RPMI CB.17 SCID mice. In this preclinical study: continuous delivery of lenalidomide resulted in significant improvements (p<0.05) in the mean time to treatment failure (TTF) in the 216 mcg/day (42 days) and 288 mcg/day (43 days) groups compared to both vehicle and IP arms.

Mean tumor volume at the end of the 27 day cycle was ~40% greater in the vehicle and IP-treated animals (1096 an 1042 mm3) compared to continuous doses of 144 mcg/day (742 mm3), 216 mcg/day (707 mm3), and 288 mcg/day (702 mm3). These differences were significant (p<0.05).

“We conducted this study to further analyze our hypothesis that changing the pharmacokinetic profile of lenalidomide may result in clinically superior pharmacodynamic outcomes,” said Jamie Oliver, the company’s Chief Medical Officer. “We are encouraged by these results and believe STAR-LLD has the potential to provide a significant benefit to patients with multiple myeloma, lymphomas, and CLL.”

Five groups of animals (n=10 per group) were implanted with RPMI 8226 cells. Overall tolerability was not different between the groups, including variability in body weight, which was acceptable across all treatment groups in both studies. In lenalidomide-resistant tumors there was no significant difference in mean TTF between vehicle and IP lenalidomide treated animals.

These data suggest that changing the delivery of lenalidomide to a continuous subcutaneous infusion improves tumor control and tumor volume in lenalidomide resistant tumors.

The company previously announced an upcoming Phase 1b/2 clinical study in multiple myeloma and is currently targeting enrollment at US sites in the first quarter of 2023.

STAR-LLD is a continuous delivery lenalidomide in development to expand the standard of care for the most common blood cancers, multiple myeloma and chronic lymphocytic leukemia (CLL). A preclinical proof-of-concept study for STAR-LLD demonstrated that MM tumors caused by human myeloma cells grew 25-fold if untreated, five-fold when treated with pulsatile i.p. lenalidomide administration and shrank by 80% with STAR-LLD over the 29-day dosing interval. The study also showed 100% efficacy (overall response rate ORR) at 144 mcg continuous LLD and 20% tumor elimination vs. 0% ORR with active control and 0% ORR with daily pulsatile once daily dosing.

STAR-LLD has successfully completed a Phase 1 clinical study. In the Phase 1 trial the plasma lenalidomide concentration (AUC) was 57% lower with STAR-LLD continuous subcutaneous (SC) delivery compared to once-daily Revlimid oral delivery. STAR-LLD was well tolerated in all subjects with no drug-related toxicity or adverse events.

Starton has completed a pre-IND meeting for STAR-LLD SC and all IND-enabling preclinical and CMC studies.

Starton expects to reference prior findings of nonclinical safety for key sections of the New Drug Application (NDA) for REVLIMID.

A clinical-stage biotechnology company focused on transforming standard of care therapies with proprietary continuous delivery technology, so people with cancer can receive continuous treatment to live better, longer. For more information, visit startontx.com.