The first cohort in a U.S. multi-center Phase 1b dose-escalation trial of a novel cancer-targeted molecular radiotherapeutic compound (I-131-CLR1404; Novelos Therapeutics, Inc.), in cancer patients with advanced solid tumors has been successfully completed. The first two-patient cohort was successfully dosed with approximately 20 mCi of I-131-CLR1404, triggering enrollment into the second cohort at approximately 40 mCi.
Iodine-131 radiolabeled CLR1404, also called HOT, is a small-molecule, broad-spectrum, cancer-targeted molecular radiotherapeutic that we believe has first-in-class potential. HOT is comprised of a small, non-pharmacological quantity of CLR1404 (COLD) acting as a cancer-targeted delivery and retention vehicle and incorporating a cytotoxic (cell-killing) dose of radiotherapy (in the form of iodine-131, a radioisotope that is already in common use to treat thyroid and other cancer types). The ongoing Phase 1b dose-escalation trial is aimed at determining the Maximum Tolerated Dose of HOT. The reserachers expect to initiate HOT Phase II efficacy trials as a monotherapy for solid tumors with significant unmet medical need as soon as a minimal efficacious dose is established, subject to additional funding. They determine such an effective dose upon calculating it from ongoing PET imaging trials in cancer patients with LIGHT (since PET imaging is quantitative, enabling determination of tumor radiation exposure at a given dose level) or seeing a tumor response in the Phase 1b trial.
Preclinical results
Preclinical experiments in vitroand in more than a dozen in vivo (in animals) models have demonstrated selective killing of cancer cells along with a benign safety profile. In view of HOT’s selective uptake and retention in a wide range of solid tumors and in cancer stem cells, its single-agent efficacy in animal models and its non-specific mechanism of cancer-killing (radiation), we are first developing HOT as a monotherapy for solid tumors with significant unmet medical need.
“Patients with advanced solid tumors need safer and more effective therapies,” said Dr. Liu. “Based on animal data, results from a completed Phase 1a dosimetry trial, and now initial data from this Phase 1b trial, HOT appears to deliver radiation directly and selectively to cancerous tumors. Data from the first cohort indicates HOT was well-tolerated, without any grade 3 or 4 toxicities, enabling enrollment of the first patient in the second cohort. HOT uptake in cancerous tumors persisted for at least 21 days. One patient with advanced prostate cancer remains on trial at two months following treatment with HOT, while another patient with advanced colorectal cancer has completed the trial,” said Glenn Liu, M.D., University of Wisconsin Carbone Cancer Center, the trial’s principal investigator. Detailed trial results are expected to be presented at a scientific venue at a later date.
“We are pleased with HOT’s safety profile and selective cancerous tumor uptake and retention in this first cohort at a dose of approximately 20 mCi,” said Kim Hawkins, Vice President of Clinical Development of Novelos. “We now look forward to evaluating HOT at approximately 40 mCi in cancer patients with advanced solid tumors, as per the trial protocol. We also look forward to adding two additional clinical investigators to the trial, Joanne Mortimer, M.D., at the City of Hope and Michael Pishvaian, M.D., Ph.D., at Georgetown University.”
“We intend to combine the data from this trial with calculation of effective doses for HOT based on quantitative positron emission tomography (PET) tumor imaging data using I-124-CLR1404 (LIGHT), our small-molecule cancer-targeted PET imaging agent,” said Harry Palmin, President and CEO of Novelos. “Together, we believe these data will enable us to commence HOT Phase 2 proof-of-concept trials in the first quarter of 2013 in cancer patients that have significant unmet medical need.”
For more information:
NCT01495663 – Dose Escalation Study of I-131-CLR1404 in Subjects With Cancer That Does Not Respond to Treatment or Has Returned.
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