A phase 2 study using metronomic gemcitabine, doxorubicin, and docetaxel plus nivolumab in advanced leiomyosarcoma and liposarcoma (NCT04535713).
Authors: Jason Ballon, Princess "Angela" Savage, Anmol Dia Agarwal, Samantha Jeffrey, Sarosh Syed, Lauren Woolsey, Vanessa Xayasak, Stella Arakelyan, Ania M. Moradkhani, Victoria S. Chua-Alcala, Steve Wong, Doris V. Quon, Sant P. Chawla, Neal Shiv Chawla, Erlinda Maria Gordon
Journal: Journal of Clinical Oncology (2025)

11515 Background: Chemotherapy agents cemcitabine, doxorubicin, and docetaxel have all demonstrated efficacy in soft tissue sarcomas (STS) but often result in significant toxicity. Therefore, we propose a combination chemo-immunotherapy regimen using metronomic low dose chemotherapy doses to reduce toxicity, with the addition of Nivolumab, a PD-1 inhibitor with demonstrated efficacy in STS. In this study, we aimed to determine the efficacy/safety of adding nivolumab to metronomic gemcitabine, doxorubicin, and docetaxel in subjects with advanced leiomyosarcoma (LMS) or liposarcoma (LPS). Methods: Objectives: Primary: To determine progression-free survival (PFS); Secondary: T evaluate the best overall response (BOR) and duration of response (DOR) by RECIST v1.1 via CT scan or MRI during the treatment period, determine progression-free survival rate (PFS) at 6 and 12 months and determine overall survival rate at 6 and 12 months Key eligibility criteria: ≥ 18 years, previously treated locally advanced unresectable or metastatic LMS/LPS, measurable disease by RECIST v1.1, acceptable hematologic and organ functions Treatment Schedule: Three-week treatment cycles with gemcitabine (600 mg/m2 max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on Day 1 and Day 8, andnivolumab (240 mg) on Day 1 only. Results: Efficacy: The intention-to-treat population (n= 41), which includes patients who received at least one dose of gemcitabine, doxorubicin, and docetaxel, was used to determine the following: Median OS =16.1 months (95% CI: 7.4 to 20.1 months) and incidence of adverse events. The modified-intention-to-treat population (n= 31), which includes patients who completed at least the first 2 treatment cycles and follow-up CT/MRI, was used to determine the following: Median PFS = 8.6 (95% CI: 3.3-12.0) months; ORR = 22.6%; DCR = 87.5%; 6-month PFS rate = 58%; 6-month OS rate = 70.7%; 12-month PFS rate = 35.5%; 12-month OS rate = 59.1%; BOR = 7 PR, 21 SD, 4 PD. Safety: 28 of 41 patients (68%) experienced Grade 3/4 TRAEs that include: thrombocytopenia (n=12), lymphocyte count decreased (n=11), anemia (n=10), neutropenia (n=9), back pain (n=4), leukopenia (n=4), fatigue (n=2), dyspnea (n=2), hypocalcemia (n=1), muscle weakness (n=1), colitis (n=1), diarrhea (n=1), anorexia (n=1), abdominal pain (n=1), alkaline phosphatase increased (n=1), nausea (n=1), bone pain (n=1), peripheral sensory neuropathy (n=1), edema (n=1). There were no unexpected adverse events. Conclusions: Taken together, the results indicate that the combination regimen of nivolumab with metronomic gemcitabine, doxorubicin and docetaxel may have synergistic activity and is an effective treatment for advanced leiomyosarcoma and liposarcoma with manageable toxicity. Clinical trial information: NCT04535713 .