Phase 1 expansion study of FF-10832 (liposomal gemcitabine) antitumor activity in patients with advanced biliary carcinomas.

4092 Background: FF-10832 has demonstrated improved pre-clinical anti-tumor activity compared to gemcitabine (GEM). Associated factors may include its prolonged circulating half-life, tumor accumulation, and immune activation.The first in human dose finding trial of FF-10832 demonstrated a tolerable safety profile and anti-tumor activity in heavily pre-treated patients (pts) with solid tumors who progressed on prior gemcitabine. A biliary tract cancer (BTC) pt maintained a PR >60 weeks after progression on prior GEM based therapy. We subsequently enrolled an expansion cohort evaluating FF-10832 monotherapy in BTC and describe the results (NCT03440450). Methods: Pts ≥18 years with advanced BTC who had progressed on up to 3 lines of therapy were treated with FF-10832 40 mg/m 2 IV Day 1 Q 21 days until disease progression or unacceptable toxicity. Response was assessed by RECIST 1.1. Modulation of immune cells (flow cytometry/multiomics) and population PK were assessed. Results: 18 pts [12M/6F; median age 68 (34-79), ECOG PS 0 (3) PS 1 (15)] were treated; median # prior therapies, 2 (1-3); all had prior GEM and 16 had progressed on prior GEM. Pts received a median of 4 (1 - 22+) cycles with a median time on study of 10.4 (3.3 -77+) weeks. FF-10832 was well-tolerated. The most common drug-related AEs were nausea, pyrexia, and decreased appetite (39% each). No Gr 4 toxicity was observed; Gr 3 AEs in >1 pt included anemia (2) and muscular weakness (2). All AEs were successfully managed using standard therapies. Two pts withdrew and 1 pt died of cholangitic sepsis before 1 st evaluation. Best overall response in 15 remaining pts was 2 PR, 8 SD, 4 PD and 1 NE. The median PFS and OS were 3.4 and 9.1 months, respectively. Both PRs had received prior GEM/platinum-based therapy: 1) a gallbladder adenocarcinoma pt achieved a 48% decrease in target lesions with FF-10832 by cycle 2, which was maintained through cycle 10; dose was reduced to 30 mg/m 2 at cycle 5 for Gr 3 muscle weakness, 2) a hilar cholangiocarcinoma pt achieved a PR by cycle 2,with complete resolution of target lesions before withdrawing. Four additional pts maintained SD ≥ 6 cycles, with 2 continuing on therapy after 9 and 26 cycles. PK was similar to that previously reported (terminal t 1/2, 30 hours), with similar log decreases observed in Ki67+ regulatory T cells and increases observed in CD8+ cells, indicative of anti-tumor immune activation. Conclusions: FF-10832 is well-tolerated and has anti-tumor activity in pts with advanced BTC who progressed on prior GEM. Although preliminary, these results of a single agent therapy compare favorably to those reported for 2 nd line combination therapies. This warrants further investigation of FF-10832 efficacy and safety in BTC patients. Clinical trial information: NCT03440450 .