PanTher Therapeutics has treated the first patient in a Phase 1b clinical trial of PTM-101, a novel thin film formulation of paclitaxel designed for direct placement over pancreatic tumors. The investigational therapy represents a significant departure from conventional chemotherapy delivery, offering continuous localized drug exposure for approximately six weeks with minimal systemic toxicity.
The clinical-stage company announced that the first patient was dosed at Virginia Mason Medical Center in Seattle, Washington, under the supervision of Drs. Vince Picozzi and William "Scott" Helton. The trial is evaluating PTM-101 as part of first-line therapy for borderline resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC).
Addressing Chemotherapy Delivery Limitations
"Powerful cancer drugs exist but their toxicity lowers maximum dose and limits dosing frequency — leaving too many opportunities for cancers to continue spreading while patients grapple with debilitating side effects," said Laura Indolfi, Ph.D., Chief Executive Officer and Co-founder of PanTher Therapeutics. "Our investigational formulations are designed to circumvent the toxic effects of systemic chemotherapy while retaining a much higher dose of the drug exclusively at the tumor, with the goal of shrinking difficult-to-treat tumors and extending patients' lives."
The rationale for localized delivery is compelling: studies have shown that only about 1% of systemically delivered chemotherapy reaches the tumor, with the remaining 99% of drug producing toxic effects on off-target tissues including neutropenia, hair loss, nausea and vomiting, and peripheral neuropathy. Pancreatic cancer presents additional challenges as it is notoriously poorly vascularized, making it extremely difficult for systemic chemotherapy to reach therapeutic levels at the tumor site.
Promising Early Results
PTM-101 is a polymeric thin film formulation of paclitaxel designed to deliver sustained high-dose therapy to the tumor site with little to no systemic exposure. A previous first-in-human Phase 1 study (ACTRN12621000881831) of PTM-101 at the 100 mg dose level, combined with standard of care chemotherapy in borderline resectable and locally advanced PDAC, reported promising tumor shrinkage and a favorable safety profile. Notably, no paclitaxel was detected systemically at any time during the study.
The previous study also demonstrated PTM-101's ability to integrate into current PDAC treatment protocols and deliver potential therapeutic benefit early in the clinical paradigm, beginning weeks before intravenous chemotherapy.
Current Trial Design
The ongoing dose escalation and expansion Phase 1b study (NCT06673017) is assessing safety, tolerability, and anti-tumor activity of PTM-101 at two higher dose levels when combined with standard of care neoadjuvant chemotherapy (FOLFIRINOX) in patients with borderline resectable or locally advanced PDAC. This non-randomized, open-label study plans to enroll approximately 30 treatment-naïve patients across multiple clinical sites in the U.S.
In addition to Virginia Mason Medical Center, trial enrollment is ongoing at Northwell Health Zuckerberg Cancer Center in Lake Success, New York; Hoag Memorial Hospital Presbyterian in Newport Beach, California; and the Barbara Ann Karmanos Cancer Institute in Detroit, Michigan.
Clinical Perspective
"PTM-101 is a novel, innovative approach to treating the primary pancreatic tumor," said Vince Picozzi, M.D., a medical oncologist and principal investigator of the Phase 1b clinical trial. "Doing so successfully is the first step towards curative therapy."
Scott Helton, M.D., a pancreatic surgeon in Seattle, Washington, emphasized the integration potential: "The ability of PTM-101 to integrate into our current PDAC care pathway is promising, offering the possibility of transforming a diagnostic step into the start of therapy, weeks before the patient can begin intravenous chemotherapy."
Technology Platform
PTM-101 is the most advanced product candidate within PanTher's portfolio of innovative formulations for continuous, high-dose, localized drug administration directly to the site of the tumor. The product is laparoscopically implanted at the tumor site and easily integrates with common minimally-invasive procedures used in staging pancreatic cancer.
PanTher's Sagittari™ platform enables the formulation of anti-cancer medicines in a wide range of flexible, polymer-based dosage forms that can be administered to the surface of a cancerous organ or implanted directly into a tumor. The drug product is tunable and engineered to continuously deliver the drug for weeks or months at a desired dose level, avoiding dose-limiting side effects of off-target delivery.
The company is additionally developing polymeric drug formulations for the treatment of a range of other solid tumor types, with PTM-101 currently being evaluated with support from the Cancer Prevention & Research Institute of Texas (CPRIT) DP220066.
