(P 126) GALLANT: A PHASE 2 STUDY USING METRONOMIC GEMCITABINE, DOXORUBICIN, NIVOLUMAB, AND DOCETAXEL AS SECOND/THIRD-LINE THERAPY FOR ADVANCED 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: This report on the modified Intent-to-treat population (n=43). This population completed at least one treatment cycle and had a follow-up CT or MRI scan at week 6. Best Overall Response = 2 CR (surgical CR), 6 PR, 30 SD, 5 PD. The disease control rate ( CR+PR+SD) was 88.4%. Median PFS was > 4.6 + (range: 1-27) months; 4 month PFS rate 60%. Median OS 6.2 months, with 4-month OS 74%. Historically, the median PFS on preceding lines of therapy was 2 (range: 1-14) months.
Safety analysis: There were no unexpected adverse events noted in this study. Grade 3/4 TRAEs include Fatigue (n=13), Nausea (n=9), Neutropenia (n=8), thrombocytopenia (n=6), Anemia (n=6).

Conclusion: Taken together, the GALLANT protocol using metronomic Gemcitabine, Doxorubicin (Adriamycin), Nivolumab, and Docetaxel (Taxotere) (1) is an effective regimen as second/third-line therapy for advanced sarcoma with no unexpected adverse events, and (2) may have synergistic activity when this metronomic chemotherapy is combined with an immune checkpoint inhibitor.