1925P Results of SOC-2082 phase II study using metronomic gemcitabine, doxorubicin, and docetaxel plus nivolumab as second/third-line therapy for advanced leiomyosarcoma

Metronomic dosing of gemcitabine, doxorubicin and docetaxel causes less severe side effects than standard chemotherapy for advanced leiomyosarcoma. Primary objective: To assess progression-free survival (PFS); Secondary objectives: (1) To evaluate the best overall response, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 12 months, and (4) Incidence of treatment-related adverse events (TRAEs). Inclusion criteria: Previously treated male and female subjects, ≥ 18 years of age, pathologically confirmed diagnosis of locally advanced, unresectable, or metastatic leiomyosarcoma, measurable disease by RECIST v1.1, and acceptable hematologic and organ functions. Exclusion Criteria: History of autoimmune disorder. Treatment schedule: Metronomic doses of 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, and nivolumab (240 mg) on Day 1 only. Repeat treatment cycles may be given every three weeks if the toxicity grade is ≤1. Efficacy (n=17). This population completed at least one treatment cycle and had a follow-up CT or MRI scan at week 6. Confirmed best overall response = 4 PR, 11 SD, 2 PD. The overall response rate was 23.5%, disease control rate (CR+PR+SD) was 88.2%. The median PFS was 6.3 (95% CI: 2.837-7.363) months; 6-month PFS rate 53%. As of data cut-off date, the median OS was >14.6 months. Safety (n=18): This population had at least one dose of study drugs. Grade 3/4 TRAEs include thrombocytopenia (50%), neutropenia (44%), white blood cell count decreased (38.9%), anemia (22.2%), nausea (16.7%), anorexia (5.6%), diarrhea (5.6%), fatigue (5.6%), rectal bleeding (5.6%), transaminitis (5.6%). There were no unexpected adverse events reported. As of data cut-off date, the median OS was >14.3 months. Taken together, the data suggest that nivolumab plus metronomic doses of gemcitabine, doxorubicin, and docetaxel (1) may have synergistic activity, and (2) is an effective second/third -line therapy for advanced leiomyosarcoma with manageable toxicity.