An open label phase IIa study evaluating the preliminary efficacy of intratumoural tigilanol tiglate (TT) in advanced and/or metastatic soft tissue sarcoma (STS)

BackgroundTT is an epoxytigliane small molecule that directly induces tumor necrosis and tumour vascular disruption via intratumoral injection. Based on promising preclinical and phase I data, this study assessed early efficacy and safety in patients with STS.MethodsPatients with recurrent or metastatic STS were enrolled in a single arm, open label phase II pilot study of intratumoral TT dosed at 28-day intervals. The primary endpoint was ablation rate (proportion of patients achieving ≥30% reduction in tumor volume) assessed via ultrasound 28 days post injection. Ablation was assessed on entire tumors or treated tumor segments in large lesions. TT was predefined as warranting further study in STS if ablation occurred in at least 2 of 10 patients. Biopsy and blood samples were obtained pre and posttreatment.ResultsEleven patients, 4 with leiomyosarcoma, 3 with myxofibrosarcoma, and one each of myxoinflammatory fibroblastic sarcoma, extraskeletal osteosarcoma, angiosarcoma, and sarcoma NOS were enrolled. All patients had at least 4 four prior lines of treatment. One patient was lost to follow up and replaced. To date, data from 5 patients are evaluable. At the 28-day primary endpoint, 3 patients demonstrated complete or partial ablation of injected tumors (60% ablation rate). Of the 12 total tumors or segments that were injected at time of data cut off, 8 were completely or partially ablated (67% objective response rate): 6/7 myxofibrosarcoma lesions (5 complete, 1 partial), 1/2 leiomyosarcoma lesions (1 complete), and 1/2 extraskeletal osteosarcoma lesions (1 partial). Injection site reactions were common (80%), most G1/2. One patient experienced a G3 AE (injection site infection). No patient withdrew due to AEs, and no deaths were reported.ConclusionsIntratumoural TT appears safe for patients with STS. Efficacy in ablating injected tumours was observed across different histologic types. The primary endpoint for a promising response was met within the first 5 evaluable patients. Results from the full 11 patient cohort will be presented. The tolerability and promising response rate warrant further investigation of TT in patients with STS either alone or in combination with other agents.Clinical trial identificationNCT05755113.Legal entity responsible for the studyQbiotics Group Inc.FundingQbiotics Group Inc.DisclosureE.K. Bartlett: Financial Interests, Institutional, Funding: Qbiotics Group, SkylineDx. C.E. Ariyan: Other, Personal, Other, Spouse employed by company: Pfizer. A. Crago: Non-Financial Interests, Personal, Advisory Role: SpringWorks Therapeutics. S.P. D'Angelo: Financial Interests, Personal, Advisory Board: Merck, Adaptimmune, Nektar, GSK, Immune Design, Pfizer, Rain Therapeutics; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, EMD Serono. R.G. Maki: Financial Interests, Personal, Advisory Board: PEEL Therapeutics, Bayer, Deciphera, Ipsen; Financial Interests, Personal, Speaker, Consultant, Advisor: MJH Life Sciences; Financial Interests, Institutional, Research Funding: Regeneron, Daiichi Sankyo, SpringWorks Therapeutics, Boehringer Ingelheim, Astex Pharmaceuticals; Financial Interests, Institutional, Advisory Board: Presage Biosciences. W.D. Tap: Financial Interests, Personal, Advisory Board: Eli Lilly, EMD Serono, Mundipharma, C4 Therapeutics, Daiichi Sankyo, Servier Pharmacueticals, Deciphera, Adcendo, Ayala, Kowa, Bayer, Epizyme, Cogent, Medpacto, Amgen, Foghorn, AmMaxBio. C.M. Kelly: Financial Interests, Personal, Advisory Role: Exicure; Financial Interests, Personal, Advisory Board: Servier, Chemocentryx, Kartos pharmaceuticals; Financial Interests, Institutional, Research Funding: Amgen, Merck. All other authors have declared no conflicts of interest.