Results of NC-6300 (nanoparticle epirubicin) in an expansion cohort of patients with angiosarcoma.

Abstract

11543 Background: NC-6300 is a polymeric micelle exhibiting increased tumor accumulation compared to small-molecule epirubicin through enhanced pharmacokinetics and controlled release within the tumor through a pH-sensitive linker conjugated to epirubicin. In a phase 1b trial, which accrued twenty-nine patients with various types of sarcoma as well as solid tumors, observed dose-limiting toxicities included thrombocytopenia, stomatitis, lung infection, and febrile neutropenia. The maximum tolerated dose and the recommended phase 2 dose were determined to be 185 mg/m2 and 150 mg/m2, respectively. The objective response rate (ORR) in soft tissue sarcoma subset (n = 17) was 18% with both angiosarcoma patients achieving partial response. To further evaluate the anti-tumor activity of NC-6300 in angiosarcoma, we conducted an expansion cohort of 10 additional angiosarcoma patients. Methods: Eligible patients, at least age 18 years old, with histologically confirmed angiosarcoma, including cutaneous and non-cutaneous variants, not amenable to curative treatment with surgery or radiotherapy were included. No more than two lines of prior systemic therapy were allowed. NC-6300 was administered at the dose of 150 mg/m2 intravenously on Day 1 of a 21-day cycle. Treatment was continued until disease progression or unacceptable toxicity. Disease assessment was performed every 6 weeks using RECIST v1.1. The primary endpoint was median progression-free survival (mPFS). Results: Ten patients (cutaneous: 2 pts; non-cutaneous: 8 pts) were enrolled and deemed evaluable. Median line of prior systemic treatment in the advanced disease setting was 1.0 and seven patients (70%) received prior anthracycline therapy. Objective response rate (ORR) was 30% (cutaneous: 1 pt, non-cutaneous: 2 pts) and mPFS was 5.4 months (95% CI: 1.2-NA). Across all angiosarcoma patients included in the phase 1 portion and expansion cohort (phase 1b portion: 2 pts, expansion cohort: 10 pts), ORR and mPFS was 42% and 7.3 months (95%CI: 3.3-NA), respectively. All patients enrolled in the expansion cohort experienced grade 3/4 AEs and no treatment related death was observed. Most frequent grade 3/4 AEs were neutropenia without fever (80%), thrombocytopenia (40%), anemia (20%) and leukopenia (20%). AEs led to NC-6300 dose reduction and medication withdrawal were seen in 70% and 10% of patients, respectively. Conclusions: Promising anti-tumor activity was observed in this cohort of patients with cutaneous and non-cutaneous angiosarcoma. The safety profile of this expansion cohort was consistent with previous clinical study results of NC-6300. Our study results warrant further development of NC-6300 for angoisarcoma. Clinical trial information: NCT03168061.