Abstract 1528TiP
Background
Leiomyosarcoma (LMS) is one of the most common and aggressive subtypes of soft tissue sarcoma in adults, with the highest risk of recurrence and decreased disease-specific survival (George S, et al. J Clin Oncol. 2018; 36:144–150). A high unmet need remains for treatment of patients with unresectable or metastatic, relapsed or refractory LMS. In a Phase 1b study (NCT03761095), unesbulin, a microtubule polymerization inhibitor, plus dacarbazine (DTIC), was evaluated in patients with unresectable or metastatic, relapsed or refractory LMS, with acceptable benefit/risk ratio to support the start of a Phase 2/3 study.
Trial design
SUNRISELMS is an international, randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of unesbulin + DTIC versus placebo + DTIC in patients with unresectable or metastatic, relapsed or refractory LMS who received ≥1 prior line of systemic therapy. Patients will be randomized 2:1 to unesbulin 300 mg orally twice weekly (BIW) in each 3-week treatment cycle plus DTIC 1000 mg/m2 intravenous (IV) once every 21 days (Q21D). Matching oral placebo BIW plus DTIC IV 1000 mg/m2 will be administered Q21D. An interim analysis will be performed when ∼36%, or 88 of the progression-free survival (PFS) events occur. Eligible patients will have unresectable or metastatic, relapsed or refractory, measurable LMS according to RECIST 1.1, and be ≥18 years. Approximately 345 patients will be enrolled: 300 patients with 1 to 3 prior lines of systemic therapy for the primary analysis and 45 patients with at least 4 prior lines of systemic therapy for the exploratory interim analysis. Randomization will be stratified by histological tumor type (uterine versus nonuterine LMS), ECOG score of 0 or 1 and lines of treatment. The primary endpoint is PFS. Key secondary efficacy endpoints include overall survival, objective response rate, disease control rate, duration of response, and safety. The study is open and recruiting patients.
Clinical trial identification
NCT05269355.
Editorial acknowledgement
Medical writing assistance, supported financially by PTC Therapeutics, Inc., was provided by Ilaria Esposito, PhD of Lighthouse Medical Communications for preparation of this abstract.
Legal entity responsible for the study
PTC Therapeutics, Inc.
Funding
PTC Therapeutics, Inc.
Disclosure
M. Ingham: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Xencor, Apexigen, Epizyme, Caris Life Sciences, PTC Therapeutics; Financial Interests, Institutional, Research Grant: Apexigen, Mirati Therapeutics, PTC Therapeutics, APIM Therapeutics, Merck, Codiak, Bioatla, Intensity Therapeutics, Astellas. J-Y. Blay: Financial Interests, Personal, Advisory Board: Bayer, Deciphera, GSK, Roche; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Invited Speaker: MSD, MSD; Financial Interests, Personal, Other, member of the supervisory board: Innate pharma; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. J. Baird: Financial Interests, Personal, Stocks/Shares, Shareholder in PTC Therapeutics, Inc stock: PTC Therapeutics, Inc.; Financial Interests, Personal, Full or part-time Employment, Employee of PTC Therapeutics: PTC Therapeutics, Inc. D. D'Silva: Financial Interests, Personal, Full or part-time Employment, PTC Therapeutics, Inc.: PTC Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares, PTC Therapeutics Stock: PTC Therapeutics, Inc. K. O'keefe: Financial Interests, Personal, Full or part-time Employment, Employee of PTC Therapeutics: PTC Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares, Employee of PTC Therapeutics: PTC Therapeutics, Inc. R. Kong: Financial Interests, Personal, Stocks/Shares, PTC Stock: PTC Therapeutics, Inc.. R. Spiegel: Financial Interests, Personal, Other, Consultant to PTC Therapeutics: PTC Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares, Stock options in PTC Therapeutics.: PTC Therapeutics, Inc. M. Wahba: Financial Interests, Personal, Stocks/Shares, Stocks in Pfizer: Pfizer; Financial Interests, Personal, Stocks/Shares, Stocks in Johnson and Johnson: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares, PTC Therapeutics, Inc.: AZS; Financial Interests, Personal, Full or part-time Employment, Contract with PTC Therapeutics: PTC Therapeutics, Inc. M. Weetall: Financial Interests, Personal, Full or part-time Employment, Employee of PTC Therapeutics, Inc.: PTC Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares, Hold stock in PTC Therapeutics: PTC Therapeutics, Inc.