Phase 2a Trial Initiated For Continuous SC Lenalidomide in R/R Myeloma

The first patient has undergone dosing for a continuous subcutaneous (SC) formulation of lenalidomide (STAR-LLD) in a phase 2a clinical trial (NCT06087653) for the treatment of relapsed/refractory multiple myeloma (R/R MM).¹ The study aims to address the challenge of hematologic toxicity and treatment discontinuation associated with standard oral lenalidomide dosing.

“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,” stated Jamie Oliver, PharmD, chief medical officer at Starton Therapeutics, in a news release.

The Rationale for Continuous Delivery

Although lenalidomide (Revlimid) remains a cornerstone of MM therapy, its clinical utility is often limited by dose-dependent myelosuppression. Neutropenia and thrombocytopenia frequently necessitate dose interruptions or reductions, potentially compromising long-term efficacy.

STAR-LLD utilizes a proprietary delivery technology designed to maintain a consistent, low-dose systemic exposure. By maintaining a meaningful minimum effective dose while avoiding the high peak plasma concentrations associated with oral administration, investigators hypothesize that STAR-LLD can mitigate toxic effects while enhancing the drug's immunomodulatory properties.

Responses Achieved in Phase 1b Trial

The transition to phase 2a follows highly encouraging phase 1b data reported at the 2025 American Association of Cancer Research annual meeting.² A cohort of 6 patients with R/R MM across 2 sites received treatment. They had a median age of 73 years and a 1:1 male/female ratio and had received a median of 2 prior lines of treatment (range, 1-7). Four had received prior lenalidomide and all had received prior bortezomib (Velcade). In the trial, they received bortezomib, lenalidomide, and dexamethasone.

Lenalidomide was administered SC at 9.6 mg per day with an ambulatory pump using a 28/28 day cycle; patients were either trained to operate and refill the pump or were managed in the clinic on Monday, Wednesday, and Friday.

The continuous delivery of low-dose lenalidomide resulted in an objective response rate (ORR) of 100%, including 1 complete response and 5 partial responses . Five patients continued to receive therapy with a median progression-free survival (PFS) of over 10 months. Notably, no drug-related hematologic toxicities (anemia, neutropenia, or thrombocytopenia) greater than grade 2 were observed over up to 12 cycles of therapy. One patient discontinued treatment due to a grade 2 skin toxicity.

Phase 2b Study Plan

The phase 2a trial is a randomized, dose-escalation study focusing on transplant-ineligible patients in their second or later line of therapy.¹ The protocol compares 3 doses of STAR-LLD SC infusion administered in combination with dexamethasone and a proteasome inhibitor (PI) against the current standard of care: daily 25 mg oral lenalidomide with the same combination. The primary end point is the safety and tolerability of the experimental arm for up to 12 months. Secondary end points include pharmacokinetics and pharmacodynamics, ORR , PFS, and overall survival.³

The study is expected to enroll 24 patients for dose escalation with an additional 45 who could be treated at the recommended phase 2 dose. Enrollment is estimated to be complete in the first half of 2027. The study is currently expanding through the Sargon Site Network, increasing from 2 to 6 investigational sites across the United States.

“Building on encouraging early clinical experience through our phase 1b trial, we look forward to advancing STAR-LLD in the next stage of development and to further establish its potential in enabling more patients to remain on therapy longer to experience the full potential benefit of treatment,” stated Oliver.

REFERENCES

1. Starton Therapeutics Inc. Starton Therapeutics announces dosing of first patient in phase 2a study evaluating STAR-LLD for the treatment of multiple myeloma. News release. Starton Therapeutics. February 19, 2026. Accessed February 24, 2026. https://tinyurl.com/mr34sty7

2. Gabrail N, Lerro K, Hussain MA, Chanan-Khan AA, Oliver JC. Continuous subcutaneous lenalidomide delivery improves the therapeutic index and avoids drug-related grade 3/4 hematologic toxicity in patients with relapsed/refractory multiple myeloma. Cancer Res. 2025;85(8_Supplement_2):LB207. doi: 10.1158/1538-7445.AM2025-LB207

3. Safety, efficacy, and pharmacokinetics of continuous subcutaneous lenalidomide in multiple myeloma (MM). ClinicalTrials.gov. Updated June 19, 2025. Accessed February 24, 2026. https://clinicaltrials.gov/study/NCT06087653