(P 122) AN UPDATE ON TNT: A PHASE-2 STUDY OF THE EFFICACY AND SAFETY OF TALIMOGENE LAHERPAREPVEC, NIVOLUMAB, AND TRABECTEDIN IN ADVANCED SARCOMA

Objective: Primary: To assess progression-free survival (PFS). Secondary: (1) To evaluate the best overall response during treatment confirmed in a 6-week follow-up, (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).

Methods: Eligible patients include patients ≥ 18 years of age with locally advanced unresectable or metastatic STS, 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 (1x10e8 PFU/ml q 2 weeks depending on tumor size) were administered. A starting dose of TVEC (1x10e6 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:There were 49 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 1-8). Best Overall Response by RECIST v1.1 (Confirmed) = 2 CR (5%), 3 PR (7.7%), 35 SD (71.4%), 9 PD (18%). One patient with a previously unresectable disease was taken for resection and found to have 100% necrosis on surgical pathology. The disease control rate (CR+PR+SD) was 81.6%. The median PFS at cutoff 1/31/2022 was 4.4 (range: 1-27 ) months; the 6 and 9-month PFS rate was 46% and 31%. Median PFS on therapy immediately preceding this trial was 2.0 months (range=1-14 months). There were sixty-three evaluable subjects for OS analysis under the Intention-to-Treat (ITT) population. 57/63 ITT patients received T, N, and TVEC. The Median OS was 7.1 (range 0-32) months; 6, 9, and 12-month OS rate: 68%, 50% and 46% respectively. Safety: There were no new safety signals noted in this study. Twenty-three patients experienced at least one Grade 3 treatment-related adverse event. The most common grade 3/4 TRAEs include anemia (n=12), increased ALT (n=8), fatigue (n=4), thrombocytopenia (n=4), neutropenia (n=4). There were no grade 3/4 TVEC injection site reactions.

Conclusion: These results suggest that the second/third-line combination of Talimogene Laherparepvec (TVEC), Nivolumab & Trabectedin is a promising alternate second/third-line therapy in achieving disease control. There were no unexpected, or severe adverse events noted.