1728P - Results of TNT: A phase II study using talimogene laherparepvec, nivolumab and trabectedin for advanced leiomyosarcoma and liposarcoma [NCT# 03886311]

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 II 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).

Methods

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). 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 months 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.

Conclusions

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.

Clinical trial identification

NCT 03886311.

Editorial acknowledgement

Legal entity responsible for the study

Sarcoma Oncology Research Center.

Funding

Amgen provided partial funding.

Disclosure

All authors have declared no conflicts of interest.