Original Article

Cancer Chemotherapy and Pharmacology

, Volume 70, Issue 5, pp 699-705

Phase I and pharmacokinetic study of IHL-305 (PEGylated liposomal irinotecan) in patients with advanced solid tumors

  • Jeffrey R. InfanteAffiliated withSarah Cannon Research Institute
  • , Vicki L. KeedyAffiliated withVanderbilt University
  • , Suzanne F. JonesAffiliated withSarah Cannon Research Institute Email author 
  • , William C. ZamboniAffiliated withUNC 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
  • , Emily ChanAffiliated withVanderbilt University
  • , Johanna C. BendellAffiliated withSarah Cannon Research Institute
  • , Wooin LeeAffiliated withUniversity of Kentucky
  • , Huali WuAffiliated withUNC 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
  • , Satoshi IkedaAffiliated withYakult Honsha, Co., Ltd.
    • , Hiroshi KodairaAffiliated withYakult Honsha, Co., Ltd.
    • , Mace L. RothenbergAffiliated withVanderbilt University
    • , Howard A. Burris IIIAffiliated withSarah Cannon Research Institute

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Abstract

Purpose

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.

Results

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.

Conclusions

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.

Keywords

PEGylated liposomal irinotecan IHL-305 Phase I Pharmacokinetic