(P 248) TNT: A PHASE 2 STUDY USING TALIMOGENE LAHERPAREPVEC, NIVOLUMAB, AND TRABECTEDIN FOR ADVANCED LEIOMYOSARCOMA AND LIPOSARCOMA (NCT # 03886311)

Objective: Background: Intratumoral injection of Talimogene Laherparepvec (TVEC) has a local oncolytic effect and evokes a cytotoxic immune response. The combination of Trabectedin (T) and Nivolumab (N) is a safe and effective therapy in soft tissue sarcoma (STS). Here, we report on the results of an ongoing Phase 2 study that aims to determine the efficacy and safety of adding TVEC to the combination of T and N in advanced leiomyosarcoma (LMS) and liposarcoma (LPS).

Objectives: Primary: To assess progression-free survival (PFS) and overall survival (OS). Secondary: (1) To evaluate the best overall response, (2) Disease control rate (3) PFS rate at 6 months, (4) OS rate at 6 months, (5) Incidence of treatment-related adverse events (TRAEs).

Methods: Eligible patients: ≥ 18 years, locally advanced unresectable or metastatic LMS and LPS, measurable disease by RECIST v1.1, at least one accessible tumor for TVEC intratumoral injection. N (3 mg/kg q 2 weeks), T (1.2 mg/m2 q3 weeks), and TVEC (1x108 PFU/ml q 2 weeks depending on tumor size) were administered. A starting dose of TVEC (1x106 PFU/ml) was initially given, followed by a total dose of 1x10e8 PFU/ml q 2 weeks depending on tumor size) three weeks later.

Results: Efficacy: Modified intent-to-treat population (n = 29): Completed at least one treatment cycle and had a follow-up CT or MRI. Median PFS 9.1 (95% CI: 5.2-13) months, Median OS 21.9 (95% CI: 14.9-28.9) months. Best Overall Response = 2 PR, 23 SD, and 4 PD; BORR = 6.9%; DCR 86.2%; 6 month PFS rate 62%; 6-month OS rate 86.2%.

Safety: Ten of 29 (34.5%) patients experienced Grade 3/4 TRAEs that include nausea (n=2), fatigue (n=2), anemia (n=2), thrombocytopenia (n=1), hypokalemia (n=1), dehydration (n=1), decreased LVEF (n=1). There were no unexpected adverse events.

Conclusion: The data indicates that the combination regimen using Talimogene Laherparepvec, Nivolumab and Trabectedin may be more effective than Trabectedin alone (Median PFS 4.1 months) as treatment for previously treated patients with advanced leiomyosarcoma and liposarcoma with manageable toxicity.