irinotecan liposome (PharmaEngine, Inc.)

Irinotecan liposome, also known as PEP02 or MM-398, is a novel nanoparticle formulation of irinotecan sucrosofate encapsulated within polyethylene glycolated liposomes. This formulation enhances its circulation time and improves pharmacokinetic properties compared to conventional irinotecan. It consists of approximately 80,000 molecules of irinotecan encapsulated in a 100-mm liposome sphere. **Pharmacological Properties:** PEP02 demonstrates several advantages over free irinotecan: * Slow clearance (mean = 0.0591 L/m²/h) * Small volume of distribution (mean = 1.8 L/m² ≈ plasma volume) * Prolonged terminal half-life (mean = 29.5 h) * Enhanced tumor biodistribution of both irinotecan and its active metabolite SN-38 * Reduced accumulation in organs associated with toxic side effects The liposomal encapsulation allows for slow release of irinotecan over time, as evidenced by plasma concentration-time profiles showing that encapsulated irinotecan matched approximately with total irinotecan levels. **Clinical Development:** PEP02 has been evaluated in several clinical trials, including: * Phase I study in advanced refractory solid tumors at doses ranging from 60 to 180 mg/m², given as a 90-minute intravenous infusion every 3 weeks * Phase II study as second-line treatment for pancreatic cancer at 120 mg/m² every 3 weeks * Randomized phase II study comparing PEP02 with irinotecan or docetaxel in second-line treatment of advanced oesophago-gastric cancer * Phase I dose-escalation study of PEP02 in combination with 5-FU and leucovorin, establishing a maximum tolerated dose (MTD) of 80 mg/m² * PEPCOL randomized non-comparative phase II study evaluating PEP02 or irinotecan in combination with leucovorin/5-FU in metastatic colorectal cancer **Efficacy and Safety:** In clinical trials, PEP02 has shown: * Moderate anti-tumor activity in gemcitabine-refractory pancreatic cancer with a 3-month survival rate of 75% * Objective response rates comparable to docetaxel and numerically greater than irinotecan in oesophago-gastric cancer * Promising tumor response when combined with 5-FU/leucovorin (FUPEP regimen) in oxaliplatin-pretreated colorectal cancer patients The most common adverse events associated with PEP02 include: * Diarrhea * Neutropenia * Nausea * Vomiting * Abdominal pain * Asthenia Based on its promising results, PEP02 (MM-398) was further evaluated in the phase III NAPOLI-1 trial for metastatic pancreatic cancer, which ultimately led to its approval as Onivyde (irinotecan liposome injection).

Brand names

Onivyde

Other names

nanoliposomal irinotecanliposomal irinotecan