A phase 2 study to investigate the efficacy and safety of acoustic cluster therapy with modified FOLFIRINOX in patients with locally advanced pancreatic cancer.

Abstract

TPS795 Background: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) face limited treatment options due to the tumor’s dense stromal microenvironment, which impedes drug penetration and reduces chemotherapy efficacy (Kane et al., 2020). Acoustic cluster therapy (ACT) is an investigational ultrasound-mediated drug delivery platform combining a proprietary intravenous formulation (PS101) with focused ultrasound to enhance chemotherapeutic delivery. PS101 consists of microclusters of perfluorobutane microbubbles and perfluoromethylcyclopentane microdroplets. After injection, diagnostic-frequency ultrasound (~2 MHz, diagnostic mechanical index (MI)) is applied over the tumor site. Upon reaching the tumor vasculature, ultrasound activation causes the microclusters to expand into transient ACT bubbles (~22 μm diameter), which deposit in <2% of the local microvasculature. Subsequent enhancement ultrasound pulses (0.5 MHz, low MI) applied for 5 minutes induce oscillation of these ACT bubbles, increasing vascular permeability and promoting transvascular and stromal penetration of co-administered chemotherapy. In vivo non-clinical studies have shown a synergistic anti-cancer effect of ACT with various chemotherapy agents in tumor xenograft models, including pancreatic cancer. In many models, ACT combined with chemotherapy produced significantly greater effects than chemotherapy alone (Ng, 2022). Final data from the Phase 1 ACTIVATE trial showed ACT improved chemotherapy efficacy in colorectal liver metastases, with a 29% tumor diameter reduction in ACT-treated patients versus 7% with chemotherapy alone in responders. Han et al. (2024) recently demonstrated the clinical value of sonochemotherapy in advanced PDAC. Hence, we are conducting a clinical trial in individuals with localized PDAC utilizing ACT. Methods: This is a Phase 2, multicenter, open-label, single-arm clinical trial (NCT06850623) using a Simon’s two-stage design (n=25) to evaluate the safety and efficacy of ACT with standard-of-care mFOLFIRINOX in treatment-naïve patients with borderline resectable or unresectable locally advanced pancreatic cancer (LAPC). The primary objective is to assess efficacy by overall response rate per RECIST v1.1. Secondary objectives include safety and tolerability, anti-tumor activity, resection eligibility post-treatment, and overall survival. Key eligibility criteria: (1) histologically or cytologically confirmed PDAC not suitable for curative surgery; (2) no prior anti-cancer treatment for PDAC; (3) tumor localizable by non-contrast ultrasound with a maximum 14 cm distance from probe to tumor margin; and (4) suitability for mFOLFIRINOX. Enrollment began in June 2025. Clinical trial information: NCT06850623 .