Abstract CT106: First-in-human phase 1 study of paclitaxel-eluting PTM-101 film in subjects with borderline resectable or locally advanced pancreatic cancers

Abstract Background Unlike many other types of cancer, improvements in the treatment of pancreatic cancer have been very limited, in part due to the inability to deliver chemotherapy to the tumor at efficacious concentrations for a prolonged time. PTM-101 is a novel biodegradable film containing paclitaxel and is designed to continuously release high concentrations of paclitaxel precisely to the site of a pancreatic tumor over one month. Methods This first in human study was conducted at one center in Australia to assess the safety, toxicity, and surgical feasibility of a single administration of PTM-101 containing 100 mg of paclitaxel. PTM-101 was sutured directly onto the pancreatic surface overlying the tumor by a surgical oncologist using standard laparoscopic equipment during a disease-staging assessment. Approximately 3 weeks after PTM-101 placement, all participants began standard of care therapy which included mFOLFIRINOX. This study enrolled 3 subjects that had treatment naïve, borderline resectable or locally advanced, pancreatic adenocarcinoma. Subjects were monitored closely for local and systemic toxicities, as well as for preliminary signals of efficacy. An independent central imaging lab reviewed CT scans to determine changes in tumor volume. Results PTM-101 was successfully implanted over the tumor site in all three subjects. In all cases, there were no adverse events reported during the procedure. Overall, PTM-101 was well tolerated with a total of five Grade 1 adverse events judged at least possibly related to the procedure or the mFOLFIRINOX. No serious adverse events (SAEs) or deaths occurred. Paclitaxel was undetectable in the circulation at all time points. Subjects were followed for 6 months. Best overall response rate according to RECIST was stable disease (2 subjects) and partial response (1 subject). An independent analysis showed that all tumors had a reduction in size in the anterior/posterior diameter, which was consistent with unidirectional paclitaxel release from PTM-101. Two of the 3 subjects had a 30% tumor volume reduction, importantly, with the initial decrease in tumor size detected prior to mFOLFIRINOX. Conclusion PTM-101 was readily implanted during diagnostic laparoscopy and was well tolerated with no SAEs or deaths reported during 6 months of follow up. This study demonstrated that a PTM-101 implant was surgically feasible, safe, resulted in no systemic paclitaxel exposure, and caused a tumor size reduction in all 3 subjects. Additional studies may demonstrate the potential for PTM-101 to be a first-line adjunct prior to neoadjuvant therapy in treatment naïve, borderline resectable or locally advanced, pancreatic cancer. Citation Format: Charles Pilgrim, Marty Smith, Ee-Jun Ban, Samantha Ellis, John Zalcberg, Benjamin Markman, Margaret Lashof-Sullivan, Laura Indolfi. First-in-human phase 1 study of paclitaxel-eluting PTM-101 film in subjects with borderline resectable or locally advanced pancreatic cancers abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT106.