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

Background

Metronomic dosing of gemcitabine, doxorubicin and docetaxel causes less severe side effects than standard chemotherapy for advanced leiomyosarcoma.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

NCT04535713.

Editorial acknowledgement

Legal entity responsible for the study

Sarcoma Oncology Research Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.