Abstract A068: 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 Background: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have limited therapeutic treatment options, largely due to the tumor’s dense stromal microenvironment, which hinders drug penetration and significantly reduces the effectiveness of systemic chemotherapy (Kane et al., 2020). Acoustic cluster therapy (ACT) is an investigational ultrasound-mediated drug delivery platform that combines a proprietary intravenous formulation (PS101) with focused ultrasound to enhance chemotherapeutic delivery. In ACT, PS101—comprised of microclusters of perfluorobutane microbubbles and perfluoromethylcyclopentane microdroplets —is injected intravenously and insonated over the tumor site using diagnostic-frequency ultrasound (∼2 MHz). Upon reaching the tumor vasculature, ultrasound activation triggers microcluster expansion into transient ACT bubbles (∼22 μm average diameter), which deposit in <2% of the local microvasculature. A subsequent enhancement ultrasound pulse (0.5 MHz, low mechanical index) applied for 5 minutes induces oscillations of these ACT bubbles, increasing vascular permeability and promoting transvascular and stromal penetration of co-administered chemotherapy. In vivo non-clinical evaluation of ACT has shown a marked synergistic anti-cancer effect with a range of chemotherapy agents and tumor xenograft models including pancreatic cancer. In many of these models, the differential effect levels observed using ACT with chemotherapy versus chemotherapy alone have been substantial (Ng, 2022). Han et al. (2024) recently demonstrated the value of sonochemotherapy in patients with advanced PDAC. Methods: This is a phase 2, multicenter, open-label, single-arm clinical trial (NCT06850623) employing a Simon’s two-stage design (n=25) to evaluate the safety and efficacy of ACT in combination with standard-of-care mFOLFIRINOX chemotherapy in treatment-naïve patients with borderline resectable or unresectable locally advanced pancreatic cancer (LAPC). The primary objective is to evaluate the efficacy of ACT with mFOLFIRINOX, as assessed by overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Secondary objectives include the evaluation of safety and tolerability; anti-tumor activity; the proportion of participants who become eligible for tumor resection following treatment; and overall survival. Key eligibility include 1) histologically or cytologically proven diagnosis of PDAC not deemed suitable for primary curative surgery and have radiographic and pathological disease consistent with inoperable LAPC or borderline resectable pancreatic cancer 2) no previous anti-cancer treatment for pancreatic cancer, 3) tumor localizable with ultrasound without contrast with a maximum distance of 14 cm between the furthest tumor margin and the probe as measured by ultrasound and 4) suitable to receive treatment with mFOLFIRINOX. Enrollment began in June 2025. Citation Format: Erin Pierce, Matt Siegel, Katie Morgan, S. Danielle. Legrand, Ragnar Bendiksen, Nicola Little, Amir Snapir, Erkut Borazanci. 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]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A068.