Abstract 132TiP
Background
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.
Trial Design
RINGSIDE (AL-DES-01) is a 2-part phase II/III study. In the open-label phase II 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 III (Part B) is a double-blind, placebo-controlled study evaluating the chosen dose regimen from phase II (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. 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. Secondary endpoints are ORR (CR and PR) by BICR based on RECIST v1.1, DOR (time from CR or PR by BICR based on RECIST v1.1 until first disease progression or death from any cause); change from baseline in GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom Scale and Impact Scale (GODDESS), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function, EuroQol 5-Dimensional (EQ-5D-3L) questionnaire index score, Patient’s Global Impression of Change (PGI-C), Brief Pain Inventory (BPI) short form; treatment-emergent adverse events (TEAEs) and serious TEAEs, and time to treatment discontinuation due to TEAE. The trial is currently enrolling.
Clinical trial identification
NCT04871282.
Editorial acknowledgement
Medical writing support provided by Laurie LaRusso, MS, ELS, Chestnut Medical Communications.
Legal entity responsible for the study
Ayala Pharmaceuticals.
Funding
Ayala Pharmaceuticals.
Disclosure
B. Kasper: Financial Interests, Personal, Advisory Board: Bayer, Blueprint, Boehringer Ingelheim, Springworks, GSK, PharmaMar, Ayala; Financial Interests, Institutional, Invited Speaker: PharmaMar, Springworks, Ayala; Non-Financial Interests, Personal, Leadership Role, Chair of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG): European Organisation for Research and Treatment of Cancer (EORTC). R.L. Jones: Financial Interests, Personal, Expert Testimony, I worked as a consultant: Adaptimmune, Bayer, Boehringer Ingelheim, Blueprint, Clinigen, Eisai, Epizyme, Daiichi Sankyo, Deciphera, Immunedesign, Lilly, Springworks, Tracon, Upto Date, PharmaMar; Financial Interests, Personal, Advisory Board, I worked as a consultant: Athenex, Astex, Immunicum, Karma Oncology, Merck, Mundipharma, Synox; Financial Interests, Institutional, Research Grant, Research grant for a clinical trial: MSD. J. Yovell: Financial Interests, Personal, Full or part-time Employment: Ayala Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Ayala Pharmaceuticals. G. Gordon: Financial Interests, Personal, Full or part-time Employment: Ayala Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Abbott, AbbVie, Ayala Pharmaceuticals. M. Gounder: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Karyopharm Therapeutics, Epizyme, Bayer, Springworks Therapeutics, Boehringer Ingelheim, TYME, Rain Therapeutics, Regeneron; Financial Interests, Personal, Speaker’s Bureau: Amgen, Karyopharm Therapeutics, Boehringer Ingelheim; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Other, Intellectual Property: GODDESS PRO Desmoid Tumor; Financial Interests, Personal, Other, Travel, accommodations, expenses: Epizyme; Financial Interests, Personal, Other: Desmoid Tumor Research Foundation, Flatiron Health, PER, Medscape, Guidepoint Global, touchIME, Med Learning Group, More Health; Non-Financial Interests, Personal, Other, Uncompensated relationship: Foundation Medicine; Non-Financial Interests, Personal, Invited Speaker, Uncompensated relationship: Athenex.