Trial in progress: TAGGED—A phase 2 study using low dose/metronomic trabectedin, gemcitabine, and dacarbazine as 2 <sup>nd</sup> /3 <sup>rd</sup> /4 <sup>th</sup> line therapy for advanced soft tissue sarcoma (NCT04535271).
Authors: Samantha Jeffrey, Jason Ballon, Anmol Dia Agarwal, Lauren Woolsey, Princess "Angela" Savage, Vanessa Xayasak, Sarosh Syed, Victoria S. Chua-Alcala, Ania M Moradkhani, Doris V. Quon, Steve Wong, Neal Shiv Chawla, Erlinda Maria Gordon, Sant P. Chawla
Journal: Journal of Clinical Oncology (2025)

TPS11589 Background: Despite significant progress in the field of cancer medicine, the prognosis of advanced soft tissue sarcoma (STS) patients remains poor. Standard of care includes surgery for resectable tumors, generally paired with adjuvant radiation and chemotherapy. Anti-neoplastic drugs trabectedin, gemcitabine, and dacarbazine, have all demonstrated efficacy in STS. However, standard doses often result in toxicity and chemoresistance. Thus, we hypothesize that a low dose/metronomic combination regimen of intravenous trabectedin, gemcitabine, and dacarbazine will produce synergistic/additive activities without additive toxicities, providing a safer and more efficacious alternative to standard chemotherapy regimens. Methods: This Phase 2 open-label single-site study (NCT04535271) will evaluate the efficacy and safety of low dose/metronomic trabectedin, gemcitabine, and dacarbazine in prolonging progression free survival in patients with advanced STS. A total of 80 previously treated patients, 18 years or older, with locally advanced, unresectable or metastatic STS will receive trabectedin 0.5mg/m2 CIV over 24 hours, gemcitabine 200 mg/m2 IV, and dacarbazine 200 mg/m2 IV on D1 and D8. Each cycle will be 3 weeks. Treatment will continue up to one year or until disease progression or unacceptable toxicity. The primary endpoint is Progression Free Survival (PFS), estimated by the Kaplan-Meier method with two-sided 95% confidence interval. Secondary endpoints include best overall response (BOR) and duration of response (DOR) by RECIST v1.1 criteria, PFS rate, overall survival (OS) rate at 4, 6, and 12 months, and incidence of treatment-related adverse events (TRAEs). The Intention-To-Treat (ITT) population, consisting of all patients who received at least one dose of each study drug, will be used for adverse event analysis. The Modified Intention-To-Treat (MITT) population, consisting of patients who completed the first 2 cycles and have had follow-up imaging, will be used for analysis of PFS, BOR, DOR, PFS, and OS. Key inclusion criteria include a pathologic diagnosis of locally advanced or metastatic STS, previously treated patients with measurable disease by RECIST v1.1, ECOG ≤ 2, life expectancy of at least 3 months, acceptable liver and renal function, and acceptable hematological and organ functions. Key exclusion criteria include patients who have progressed with all three study drugs, known hypersensitivity to any of the three study drugs, currently receiving treatment or are &lt;14 days since ending treatment with another investigational device or drug study, pregnant or breastfeeding or who have plans to become pregnant, breastfeed, or unwilling to use female or male contraception. The study has enrolled 13 of 80 patients and is actively recruiting. Clinical trial information: NCT04535271 .