KEY TAKEAWAYS
- The phase II trial evaluated TVEC in addition to T and N for advanced LMS, with a primary objective.
- Patients were given N, T, and TVEC every 2 weeks, starting with a low dose of TVEC that was increased 3 weeks later.
- The study found that trabectedin was effective in treating leiomyosarcoma but also had a high rate of side effects.
- The study concluded that combination therapy may be best for advanced LMS, especially for HR+ uterine LMS.
Talimogene Laherparepvec (TVEC) is an oncolytic virus that can kill tumor cells and stimulate the immune system. Trabectedin (T) and Nivolumab (N) are safe and effective treatments for soft tissue sarcoma (STS). TNT is a phase II trial that evaluated TVEC in addition to T and N for advanced leiomyosarcoma (LMS), with a primary objective to assess progression-free survival (PFS) & secondary.
Patients with locally advanced unresectable or metastatic LMS received N (3 mg/kg q2 weeks), T (1.2 mg/m2q3 weeks), and TVEC (1×108PFU/ml q2 weeks based on tumor size).
The study demonstrated that the treatment regimen was effective in 11 evaluable subjects (mITT) who 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). Two patients achieved a partial response (PR), and 9 achieved stable disease (SD). The disease control rate (PR+SD) at week 6 was 100%. Median PFS: 7 months (range: 3-18); 6-month PFS rate: 55%. The median OS was 18.2 months (range: 4-32); the 6-month OS rate was 91%—no conversion from unresectable to resectable tumor. The response was unrelated to PD-L1, but both PR patients were ER+/PR+ with uterine LMS. OS analysis (ITT population, n=15, received at least one dose of study drug): Median OS: 12 months (range 0-32); 6-month OS rate: 60%.
Among 15 patients, 8 (53.3%) experienced >Grade 3 TRAEs related to Trabectedin use. Grade 3 TRAEs: anemia (n=3), thrombocytopenia (n=2), neutropenia (n=1), increased ALT (n=1), increased GGT (n=1), decreased LVEF (n=1), myalgia (n=1). Grade 4 TRAE included thrombocytopenia (n=1).
The study concluded that combination therapy may be best for advanced LMS, especially for HR+ uterine LMS. (Trabectedin alone for LMS= 4.3 mos; Dacarbazine alone = 1.6 mos; Demetri 2015).
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.11556?af=R
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03886311
Neal Shiv Chawla, Nadezhda Omelchenko, Elan Younesi, Chrysler Valencia, Amir Ahari, Ania Moradkhani, Victoria Chua, Don Brigham, Sant P. Chawla, and Erlinda Maria Gordon | Journal of Clinical Oncology 2023 41:16_suppl, 11556-11556
