(P 101) AN OPEN LABEL PHASE IIA STUDY EVALUATING THE PRELIMINARY EFFICACY OF INTRATUMORAL TIGILANOL TIGLATE (TT) IN ADVANCED AND/OR METASTATIC SOFT TISSUE SARCOMA (STS, NCT05755113)

Objective: TT 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.

Methods: Patients 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.

Results: Eleven 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 3 prior lines of treatment. One patient was lost to follow up and replaced. At the 28-day primary endpoint, 7 patients demonstrated complete or partial ablation of injected tumors (70% ablation rate, FIG 1). Of the 26 total tumors or segments that were injected, 18 were completely or partially ablated (69% objective response rate): 11/13 myxofibrosarcoma lesions (8 complete, 3 partial), 3/7 leiomyosarcoma lesions (1 complete, 2 partial), 1/2 extraskeletal osteosarcoma lesions (partial), 2/2 myxoinflammatory fibroblastic sarcoma (1 complete, 1 partial), 1/1 angiosarcoma (partial). In ongoing follow up, one patient with angiosarcoma and one with myxoinflammatory fibroblastic sarcoma experienced complete responses rendering them free of disease. Injection site reactions were common (90%), most G1/2. One patient experienced a G3 AE (injection site infection). No patient withdrew due to AEs, and no deaths were reported.

Conclusion: Intratumoural TT appears safe for patients with STS. Efficacy in ablating injected tumours was observed across numerous histologic types, exceeding the primary endpoint for a promising response. The tolerability and promising response rate warrant further investigation of TT in patients with STS either alone or in combination with other agents.