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e23570 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 an update on 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). Objectives: Primary: To assess progression-free survival (PFS). Secondary: (1) To evaluate the best overall response, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 9, and 12 months, (4) Incidence of conversion from unresectable to the resectable tumor, and (5) Incidence of treatment-related adverse events (TRAEs). Patients and Methods: Eligible patients included patients ≥ 18 years of age with locally advanced unresectable or metastatic LMS, measurable disease by RECIST v1.1, and at least one accessible tumor for TVEC intratumoral injection. N (3 mg/kg q2 weeks), T (1.2 mg/m2 q3 weeks), and TVEC (1x10 8 PFU/ml q 2 weeks depending on tumor size) were administered. A starting dose of TVEC (1x10 6 PFU/ml) was initially given, followed by a total dose of 1x10 8 PFU/ml q 2 weeks depending on tumor size) three weeks later. Results: Efficacy: Per protocol, there were 17 evaluable subjects (Modified Intention to Treat mITT patients who had completed at least one treatment cycle and had a follow-up CT scan). The median number of prior lines of therapy was 4 (range 1-9). The disease control rate (PR+SD) was 94% with 1 PR, and 15 SD. The median PFS was 8.0 months (95% CI:4.8-11.28) with a 6-month PFS rate of 71%; median OS 19.2 months (95% CI:12.7- 25.7); 6-month OS rate, 82%. Safety: 22 patients (Intention to treat ITT who had received at least one-time drug administration) were evaluated for safety analysis. The > Grade 3 TRAEs include anemia (n = 3), thrombocytopenia (n = 3), neutropenia (n = 1), increased ALT (n = 1), increased GGT (n = 1), decreased LVEF (n = 1), dehydration (n = 1), hyponatremia (n = 1). There were no new safety signals noted in this study. Conclusions: Taken together, the data confirms our previous report that (1) the combination regimen using Talimogene laherparepvec, Nivolumab & Trabectedin may be more effective and treatment for previously treated patients with advanced leiomyosarcoma with manageable toxicity, and (2) The best responders are patients with HR+ uterine LMS. Clinical trial information: NCT03886311 .
Chawla et al. (Sat,) studied this question.