(P 555) A PILOT PHASE II STUDY TO EVALUATE THE SMALL MOLECULE TIGILANOL TIGLATE IN PATIENTS WITH ADVANCED SOFT TISSUE SARCOMA: CLINICAL TRIAL IN PROGRESS

Objective: Tigilanol tiglate is an epoxytigliane small molecule that induces tumor cell necrosis and tumor vascular disruption with potential to induce systemic immunity via immunogenic cell death when injected intratumorally. In a Phase I study, tigilanol tiglate was well tolerated (96% of adverse events were mild to moderate), and clinical activity was observed (four patients had a complete response and three patients had partial responses) in nine tumour types, with abscopal tumor responses in two patients (Panizza et al., 2019). One patient with angiosarcoma of the nasal bridge, who had been recommended for a total rhinectomy, had a complete response from a single injection of tigilanol tiglate 43 days post-injection. Three punch biopsies at 12 weeks revealed no residual tumor, the patient was disease free as assessed by CT scan at 25 months, and clinically disease free at 30.5 months post-injection (Panizza et al., 2019). Based on these promising early results, a trial has been designed to investigate the preliminary efficacy of tigilanol tiglate specifically in patients with advanced and/or metastatic soft tissue sarcomas.

Methods: This is a single arm, open label pilot Phase II study of intratumoral tigilanol tiglate in 10 to 15 patients with advanced and/or metastatic soft tissue sarcoma. The primary objective is to evaluate the proportion of patients who achieve partial (≥30% response) or complete response of the injected tumor as assessed by ultrasound measurement. Secondary objectives are safety, tolerability, and pharmacokinetics. Exploratory objectives are to estimate tumor recurrence rates at 6 months and investigate correlative markers of tumor response in pre- and post-treatment biopsy and blood samples.
Patients with both resectable and unresectable sites of disease are eligible. Patients with unresectable tumor(s) may receive repeat treatments of tigilanol tiglate (administered at 0.5 mL / 1.0 cm3 tumour, up to 3.6 mg/m2) at 28-day intervals up to a maximum of five treatments.
Patients who are eligible for surgery will receive a single intratumoral treatment with tigilanol tiglate. Surgery may then be scheduled 28 days after injection, if it remains the most suitable treatment option at the discretion of the investigator. If the injected tumor shows a complete response (assessed as 100% reduction in tumour volume), patients will be monitored for recurrence.

The trial is currently open to enrolment (NCT05755113). At the time of submission, one patient with a regionally recurrent myxofibrosarcoma has been treated, and a second patient is in screening.

Results: Not applicable

Conclusion: Not applicable