Intezyne Technologies Initiates First-In-Human Trials for Topoisomerase 1 Inhibitor IT-141
(NCT03096340)
Program overview
IT-141 leverages Intezyne's proprietary nanoparticle technology (IVECT) to deliver SN-38, an extremely potent topoisomerase-1 (TOP-1) inhibitor, directly to tumors.
ABOUT Topoisomerase-1 (TOP-1) Inhibitors
Validated anti-cancer target in a wide variety of oncology indications:
Pfizer's Camptosar® (irinotecan)
FDA-approved for metastatic colorectal cancer (mCRC) in 1996
Irinotecan metabolization into SN-38 is unpredictable due to patient-to-patient variability
$969M peak sales in 2008
Remains on the WHO Model List of Essential Medicines
Merrimack's Onivyde® (liposomal irinotecan)
FDA-approved for gemcitabine-resistant advanced (metastatic) pancreatic cancer in 2015
Still suffers from irinotecan-based variability
Acquired January 2017 by Ipsen for $1B ($0.5B upfront)
Novartis's Hycamtin® (topotecan)
FDA-approved for ovarian and small cell lung cancer (SCLC)
$1.7B peak sales
ABOUT Irinotecan
SN-38 is a potent TOP-1 inhibitor
SN-38 is water-insoluble, meaning it cannot be directly administered
Irinotecan is a water-soluble produg that metabolizes into SN-38 once administered
Metabolizes into SN-38 once administered, but somewhat unpredictably
Mathijssen, R.H., et. al., Clin. Cancer Res., 2001, 7, 2182-2194.
ABOUT Colorectal Cancer
8% of cancer (135,000), 8.4% (50,000) of cancer deaths
4th most prevalent cancer; 2nd leading cause of cancer mortality
5-year survival rate of 65% overall; 11% for metastatic (Stage IV) disease
Limited therapeutic innovation in past decade
Eligible for Breakthrough Therapy Designation
IT-141 Development Rationale
Camptosar® (irinotecan), which metabolizes inefficiently into SN-38, is one of the few effective treatments for colorectal cancer
Still widely used in the treatment of colorectal cancer, despite being off-patent
Used off-label in the treatment of breast, gastric, lung, and pancreatic cancers
IT-141 patients should be able to tolerate substantially higher doses of SN-38, resulting in significantly improved patient outcomes
Potential to treat irinotecan-refractory patients
preclinical Efficacy in hct116 (colorectal) xenograft model
Bakewell, S.J.; et. al., Nanomedicine: Nanotechnology, Biology, and Medicine, 2017, 13, 1353-1362.
Phase 1 Clinical Trial
Safety and Pharmacokinetic Study of IT-141 in Monotherapy in Patients With Advanced Cancer
(NCT03096340)
Phase 1 open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of IV-infused IT-141 in patients with recurrent or refractory solid tumors
Study Design
2Q17 through 3Q18
Study Period
Primary – Safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD)
Secondary – To determine tumor response by RECISTv1.1, estimate pharmacokinetic (PK) parameters, and explore imaging and pharmacodynamic endpoints which may be of use in the further development
Endpoints
Mary Crowley Cancer Center, Dallas, TX
Seattle Cancer Care Alliance, Seattle, WA
Trial Sites
John Nemunaitis, M.D., Mary Crowley Cancer Center
Kit Wong, M.D., Seattle Cancer Care Alliance
Lead Investigators
Up to 40
No. of Participants
Intravenous