Phase 1b Safety and Antitumor Activity of PLM60 (pegylated Liposomal Mitoxantrone) in NHL.

e19503 Background: PLM60 is a novel liposomal pegylated nanoparticle formulation of conventional mitoxantrone (cMI) that showed improved PK properties, good tolerability, and potential efficacy versus cMI in patients with advanced lymphoma and sarcoma at doses of 14 and 16 mg/m2, providing a rationale for further evaluation. Methods: Randomized, open-label, Phase 1b dose escalation study to characterize safety and antitumor activity of PLM60 (18, 20, 22, 24 mg/m2) once every 28 days up to 4 cycles in patients with advanced/refractory NHL confirmed by pathology and/or cytology. Tumor assessments per Cheson 2007 criteria were at baseline and end of 2nd and 4th cycle. Results: Heavily pretreated Asian subjects (mean age 54 yrs; range 29-71 yrs; 9 males/8 females) were treated; 17 were evaluated for safety and 11 for response (4 withdrew, 2 lost to follow-up). Prior cumulative anthracycline use: 41 to 448 mg/m2. There was 1 SAE (Gr3 multiple lacunar infarction considered doubtfully related to treatment) at 24 mg/m2 and 1 DLT (Gr4 neutropenia) at 20 mg/m2; no MTD was reached at doses of 18-24 mg/m2. Most AEs were Gr1-2, few were Gr3, and 1 was Gr4 during the DLT observation period. Most common AEs were expected myelosuppression that tended to be more frequent and severe with higher doses. No subject had clinically significant decreases in LVEF from baseline or ECG abnormalities during or post treatment. Responses were seen in 4 of 11 evaluable subjects including 2 CRu at 22 mg/m2 and 2 PR at 18 mg/m2. Conclusions: PLM60 had good tolerability and therapeutic effect with no cardiotoxicity findings in patients with advanced NHL. AEs were minimal compared with those expected in a heavily pretreated population with previous anthracycline use. Number Gr3 Hematologic Events 18 mg/m2 N = 3 20 mg/m2 N = 7 22 mg/m2 N = 4 24 mg/m2 N = 3 WBC count ↓ 1 2 2 1 Neutrophil ↓ 2 3 2 2 Lymphocyte ↓ 2 4 2 1 Platelet ↓ 0 1 0 1