(P 117) INTERIM ANALYSIS OF PHASE 2 STUDY: A METRONOMIC REGIMEN USING GEMCITABINE, DOXORUBICIN, DOCETAXEL AND NIVOLUMAB FOR ADVANCED LEIOMYOSARCOMA (NCT04535713)

Objective: Metronomic dosing of gemcitabine, doxorubicin and docetaxel causes less severe side effects than standard chemotherapy for advanced leiomyosarcoma. Hypothesis: The addition of nivolumab to this regimen will have synergistic effects and improve treatment outcomes.

Primary objective: To assess progression-free survival (PFS); Secondary objectives: (1) To evaluate 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).

Methods: 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 disease control rate (CR+PR+SD) was 88.2%. Median PFS was 6.3 (95% CI: 2.837-7.363) months; 6-month PFS rate 53%. Kaplan Meir curve for PFS is shown in Figure. Median OS for ITT population (n=18) was 15.5 (95% CI: 5.48-25.12) months, with 6-month OS 94%. As of data cut-off date, median OS for mITT population has not yet been reached.
Safety (n=18): Grade 3/4 TRAEs include thrombocytopenia (n=9), neutropenia (n=8), white blood cell count decreased (n=7), anemia (n=4), nausea (n=3), anorexia (n=1), diarrhea (n=1), fatigue (n=1), rectal bleeding (n=1), transaminitis (n=1). There were no unexpected adverse events reported.

Conclusion: Taken together, the data suggests that nivolumab plus metronomic doses of gemcitabine, doxorubicin, and docetaxel (1) may have synergistic activity, and (2) is a promising second/third line combination regimen for advanced leiomyosarcoma with manageable toxicity.