(P 549) DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL OF AL102 FOR TREATMENT OF PROGRESSING DESMOID TUMORS: THE RINGSIDE PHASE 3 STUDY DESIGN

Objective: There is an unmet need for effective systemic therapy for desmoid tumors (DT, aggressive fibromatosis) that provides durable tolerability, symptom improvement, and tumor regression. Gamma secretase inhibitors (GSIs) demonstrate antitumor activity against DT. AL102 is a potent, orally available, selective GSI under investigation as an antineoplastic agent.

Methods: RINGSIDE (AL-DES-01) is a 2-part Phase 2/3 study. In the open-label Phase 2 study (Part A), adults with progressing DT (≥10% unidimensional growth within 18 months or DT-related pain requiring non-opioid medication) were randomized to three dosing regimens: 1.2 mg once daily, 2 mg intermittent BIW (2 days on 5 days off), or 4 mg intermittent BIW. RINGSIDE Phase 3 (Part B) is a double-blind, placebo-controlled study evaluating the chosen dose regimen from Phase 2 (1.2 mg once daily) in adults and adolescents (≥12 years of age) with recurrent or treatment-naïve histologically confirmed progressing DT per investigator. For eligibility, progression is defined as ≥20% measured by MRI or CT scan according to RECIST v1.1 within 12 months of the screening visit. Planned enrollment is for ≈156 subjects globally to be randomized 1:1 to either AL102 1.2 mg once daily or placebo. Randomization will be stratified according to tumor location: intra-abdominal vs. extra-abdominal (including abdominal wall). Subjects will undergo MRI or CT scans (using the same modality throughout the study) every 12 weeks to assess tumor response according to RECIST v1.1 by blinded independent central review (BICR). The primary endpoint is progression-free survival (PFS) by BICR based on RECIST v1.1. Primary and secondary endpoints are summarized in Table 1. The trial is currently enrolling.

Results: Not applicable

Conclusion: Not applicable