KANSAS CITY, Mo.—In what could be a game-changer for bladder cancer patients, biotech CicloMed LLC has released optimistic first-time results from recently completed Phase 1 safety, dose tolerance, pharmacokinetics and pharmacodynamics trials of fosciclopirox in advanced solid-tumor patients at four U.S. sites. The company also initiated a fosciclopirox expansion cohort study in cisplatin-ineligible, muscle-invasive bladder cancer (MIBC) patients scheduled for cystectomy, ongoing at two U.S. sites. Fosciclopirox is the proposed international nonproprietary name for Ciclopirox Prodrug, or CPX-POM.
In February, CicloMed presented two posters at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) in San Francisco, where results from the first-in-human, Phase 1 dose-escalation study in patients with advanced solid tumors were presented.
“The first-in-human, Phase 1 dose-escalation study demonstrated fosciclopirox was well tolerated, achieved significant systemic and urinary tract concentrations of its active metabolite—ciclopirox—at well-tolerated doses, with evidence of pharmacologic activity,” said Scott J. Weir, acting chief scientific officer of CicloMed. “The expansion cohort study now underway provides an opportunity to characterize the pharmacologic activity of fosciclopirox directly in bladder tumor tissue in a neoadjuvant setting.”
Bladder cancer “has the highest recurrence rate of all known malignancies, requiring patients typically to endure a lifetime of monitoring, surgical procedures and chemotherapy/immunotherapy treatments,” Weir explains. “Depending on the stage and grade, standards of care for NMIBC [non-MIBC] call for surgical resection of tumors and drug therapy; for MIBC restricted to the bladder, neoadjuvant chemotherapy followed by cystectomy (removal of the bladder) is standard of care. Locally or systemically advanced MIBC requires systemic chemotherapy and immunotherapy.”
With fosciclopirox, CicloMed foresees a less-invasive treatment for the patient compared to standard care.
Preclinical results of fosciclopirox in 2019 gave the CicliMed team the confidence that they were on the right track to begin the next stage.
“In vitro, fosciclopirox demonstrated antitumor activity in high-grade human urothelial cancer cell lines,” Weir remarks. “And in a mouse model of bladder cancer, fosciclopirox treatment resulted in significant reductions in tumor size, a migration to lower-stage tumors and evidence of pharmacologic activity in bladder tumor tissue.”
According to Weir, the expansion cohort study is currently open at two U.S. sites. The objectives of the expansion cohort study are to characterize the safety, pharmacokinetics and pharmacodynamics of fosciclopirox at the RP2D in bladder cancer patients.
“We expect results from the current Phase 1 expansion cohort by year-end 2020,” Weir reports. “As to other timelines, we are working through a carefully defined clinical plan designed in consultation with our clinical advisory board, comprised of leading bladder cancer experts, as well as guidance provided by the FDA, to date. We will continue to develop and refine the development program based on the results of early-phase clinical trials.
“The results from the recently completed Phase 1 dose escalation study along with results from the ongoing expansion cohort study will be reviewed with the U.S. Food and Drug Administration (FDA) to design and execute late-stage clinical trials necessary to support registration,” he continues. “We cannot predict the outcome of these studies or ultimate FDA approval. However, at this stage we envision that fosciclopirox would be administered in combination with standard-of-care surgical, chemotherapy and immunotherapy modalities to improve treatment outcomes.”
In a poster of the study by lead author Dr. Manish R. Patel, it was noted that fosciclopirox is being developed for the treatment of non-muscle invasive and muscle invasive bladder cancer. CPX-POM selectively delivers its active metabolite, ciclopirox, to the entire urinary tract following systemic administration.
Nineteen patients were enrolled in the Phase 1 study. The starting dose of 30 mg/m2 was administered once daily on days 1 through 5 of each 21-day treatment cycle. Doses were escalated to 1200 mg/m2. The maximum-tolerated dose was determined to be 900 mg/m2, which is currently being evaluated in the expansion cohort study in cisplatin-ineligible, muscle-invasive bladder cancer patients scheduled for cystectomy.
Dr. John A. Taylor III, co-leader of the Drug Discovery, Delivery and Experimental Therapeutics program at the Kansas University (KU) Cancer Center and principal investigator for the expansion cohort study, stated, “Bladder cancer patients today face limited options, and treatments often have difficult impacts on their quality of life. This study will provide important data on potential benefits of fosciclopirox, while aiding in planning for subsequent pivotal trials characterizing safety and efficacy.”
Fosciclopirox was discovered by scientists at The KU Cancer Center, a National Cancer Institute designated cancer center, and the Institute for Advancing Medical Innovation (IAMI), the cancer center’s product development enterprise. CicloMed was formed in 2016 as a public-private partnership between BioNOVUS Innovations LLC and IAMI, with fosciclopirox as the partnership’s lead drug development candidate.