(P 396) EVALUATING THE SAFETY AND EFFICACY OF METRONOMIC GEMCITABINE, DOXORUBICIN, AND DOCETAXEL PLUS NIVOLUMAB IN PREVIOUSLY TREATED ADVANCED LEIOMYOSARCOMA AND LIPOSARCOMA: A PHASE 2 STUDY (NCT04535713)

Objective: Standard chemotherapy doses often cause unacceptable toxicity in soft tissue sarcoma (STS) patients. To decrease toxicity, this phase 2 trial employs metronomic doses of gemcitabine, doxorubicin, and docetaxel, and adds PD-1 inhibitor nivolumab, for previously treated advanced leiomyosarcoma (LMS) or liposarcoma (LPS).

Objectives: Primary: Determine progression-free survival (PFS); Secondary: Evaluate best overall response (BOR) and duration of response (DOR) by RECIST v1.1, Determine progression-free survival (PFS) and overall survival (OS) at 6 and 12 months

Methods: Schedule: 3-week cycle. Gemcitabine (600 mg/m2; max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on days 1 and 8, and nivolumab (240 mg) on day 1.

Key eligibility criteria: ≥ 18 years, previously treated locally advanced unresectable or metastatic LMS/LPS, measurable disease by RECIST v1.1, acceptable hematologic/organ function

Results: Efficacy: 41 patients who received at least one dose of each agent were evaluated to determine: Median OS =16.1 months (95% CI: 7.4-20.1 months). 31 patients who completed at least 2 treatment cycles and follow-up imaging were used to determine: Median PFS = 8.6 (95% CI: 3.3-12.0) months; ORR = 22%; DCR = 87.5%; 6-month PFS rate = 58%; 6-month OS rate = 70.7%; 12-month PFS rate = 35.5%; 12-month OS rate = 59.1%; BOR = 7 PR, 21 SD, 4 PD.

Safety: 28 of 41 patients (68%) experienced Grade 3/4 TRAEs: thrombocytopenia (n=12), lymphopenia (n=11), anemia (n=10), neutropenia (n=9), , leukopenia (n=4), back pain (n=4), fatigue (n=2), dyspnea (n=2), hypocalcemia (n=1), muscle weakness (n=1), colitis (n=1), diarrhea (n=1), anorexia (n=1), abdominal pain (n=1), alkaline phosphatase increased (n=1), nausea (n=1), bone pain (n=1), peripheral sensory neuropathy (n=1), edema (n=1). No unexpected or Grade 5 adverse events were observed.

Conclusion: The combination of metronomic gemcitabine, doxorubicin, and docetaxel plus nivolumab may be a synergistic regimen and may be as effective as standard first-line therapy for advanced LMS and LPS with manageable toxicity.