(P 250) UPDATE ON GALLANT: A PHASE 2 STUDY USING METRONOMIC GEMCITABINE, DOXORUBICIN AND DOCETAXEL PLUS NIVOLUMAB IN PREVIOUSLY TREATED SARCOMA (NCT04535713)

Objective: Primary objective: To assess progression-free survival (PFS); Secondary objectives: (1) To evaluate best overall response during treatment period confirmed in a 6-week follow-up, (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 sarcoma, 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=74). This population completed at least two treatment cycle and had a follow-up CT or MRI scan at week 6. Best Overall Response = 1 CR, 13 PR, 50 SD, 10 PD. The disease control rate (CR+PR+SD) was 86%. Median PFS was 8.2 (95% CI: 6.4-10.0) months; 6-month PFS rate of 60% and 9-month PFS rate of 46%. Median OS was 17.6 (95% CI: 13.7-21.5) months, with 6-month OS of 84% and 9-month OS of 68%. Safety (n=76): Grade 3/4 TRAEs include thrombocytopenia (n=26), white blood cell count decreased (n=17), neutropenia (n=16), fatigue (n=15), anemia (n=13), nausea (n=9), anorexia (n=5), diarrhea (n=2), emesis (n=1), febrile neutropenia (n=1), sepsis (n=1), rectal bleeding (n=1), transaminitis (n=1), dizziness (n=1), shortness of breath (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) by indirect comparison, may be as effective as standard first line therapy for advanced sarcoma with manageable toxicity.