Anti-tumor activity of FF-10850 (liposomal topotecan) in patients with advanced Merkel cell carcinoma.

9581 Background: FF-10850 is a novel liposomal topotecan with increased intratumoral accumulation and robust pre-clinical activity. The prolonged t 1/2 (27 hours) supported a twice-monthly dosing schedule in the first in human dose finding trial (NCT04047251), with anti-tumor activity demonstrated in heavily pre-treated patients (pts) with solid tumors; pts remained on study up to 20 months. Common AEs were nausea and fatigue, with manageable hematologic toxicity. A Merkel cell carcinoma (MCC) pt maintained a PR for 33 weeks after progression on prior topotecan and PD-1-directed therapy. Because MCC pts who have progressed or are ineligible for anti-PD-1 therapy have few effective systemic treatment options, we evaluated FF-10850 in an MCC expansion cohort. Results are reported for all MCC pts on study. Methods: Pts ≥18 years with advanced MCC were treated with FF-10850 2 mg/m 2 IV on Days 1 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Pts must have progressed on or have been ineligible for all standard therapy and treated with or ineligible for PD-1 based therapy. In expansion, pts who progressed on camptothecin therapy within 6 months were excluded; prior etoposide was allowed. Response was assessed by RECIST 1.1. Results: 12 pts 8M/4F; median age 70 (58-84), ECOG PS 0 (5)/PS 1 (7) were treated. Baseline disease (n): unresectable stage IIIA (1), IV (10)/IVB (1). The median # of prior therapies was 1 (0-5), 1 had prior topotecan; 2 pts had no prior therapy, one due to rheumatoid arthritis (RA) and another due to solid organ transplant. Common drug-related AEs were anemia (50%), nausea (50%), fatigue (42%), and thrombocytopenia (25%). One pt each had related Gr 3 anemia and neutropenia; no related Gr 4 toxicity was observed. Three pts had infusion-related reactions; one that did not restart treatment. Two pts left study before RECIST evaluation: one withdrew to hospice care, and one died of an unrelated MI after the first dose of FF-10850 following a clinically significant anti-tumor response 2 weeks after the single dose. Best overall response in 10 RECIST evaluable pts was: 1CR, 1 PR, 4 SD and 4 PD; disease control rate (CR+PR+2 consecutive SD) was 50%. Three pts remain on study: one that achieved a CR after 2 cycles maintains CR after 14 cycles, and 2 pts maintain durable SD after 6-12 cycles. The median (range) time on study was 9.4 (3.1-50.9) weeks; median PFS and OS were 7.5 (95% CI:1.2-NR) and 10.7 (95% CI:2.1-NR) months, respectively. Conclusions: FF-10850 has demonstrated encouraging preliminary activity in both pre-treated and treatment naïve MCC. The regimen of 2 mg/m 2 every 2 weeks is tolerable with manageable hematologic side effects. PFS and OS in this small study compare favorably with that reported for cytotoxic agents in 2 nd line pts of 3 and 10 months, respectively. Further exploration of FF-10850 in MCC may offer a novel treatment option for this rare disease. Clinical trial information: NCT04047251 .