Phase I and pharmacokinetic study of IHL-305 (PEGylated liposomal irinotecan) in patients with advanced solid tumors
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IHL-305 is a novel PEGylated liposome containing irinotecan. This study examined the safety profile and pharmacokinetics of IHL-305 and established the maximum tolerated dose and recommended phase II dose (RP2D).
Patients and methods
In a standard 3 + 3 design, IHL-305 was administered IV on day 1 of a 28-day treatment schedule. Subsequently, a 14-day treatment schedule was also explored. Two patient populations were evaluated separately: Patients with at least one wild-type (wt) allele of UGT1A1 (UDP glucoronosyltransferase 1A1) wt/wt or wt/*28 as one group (referred to as UGT1A1 wt group) and patients with UGT1A1*28 homozygous variant (*28/*28) as another group.
Sixty patients were treated: 42 on the 28-day schedule and 18 on the 14-day schedule. Seven patients were homozygous variant (*28/*28). In the UGT1A1 wt group, the MTD and RP2D of IHL-305 was 160 mg/m2 every 28 days and 80 mg/m2 every 14 days. DLTs included nausea, vomiting, diarrhea, and neutropenia. The most common adverse events were nausea (75 %), vomiting (52 %), diarrhea (62 %), anorexia (57 %), and fatigue (57 %). At the MTD for both schedules, IHL-305 administration resulted in a high and prolonged exposure of sum total irinotecan, released irinotecan, and SN-38 in plasma. One partial response was observed in a patient with breast cancer and eight patients had stable disease for >6 months.
IHL-305, a novel preparation of irinotecan encapsulated in liposomes, can be safely given to patients in a repeated fashion on a 4- or 2-week dosing schedule.
- Phase I and pharmacokinetic study of IHL-305 (PEGylated liposomal irinotecan) in patients with advanced solid tumors
Cancer Chemotherapy and Pharmacology
Volume 70, Issue 5 , pp 699-705
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- PEGylated liposomal irinotecan
- Phase I
- Industry Sectors
- Author Affiliations
- 1. Sarah Cannon Research Institute, 250 25th Avenue, Suite 200, Nashville, TN, 37203, USA
- 2. Vanderbilt University, Nashville, TN, USA
- 3. UNC Lineberger Comprehensive Cancer Center, UNC Eshelman School of Pharmacy, Carolina Center for Cancer Nanotechnology Excellence, UNC Institute for Pharmacogenomics and Individualized Therapy, The University of North Carolina, Chapel Hill, NC, USA
- 4. University of Kentucky, Lexington, KY, USA
- 5. Yakult Honsha, Co., Ltd., Tokyo, Japan