Abstract A132: A Phase 2 Study to Investigate the Efficacy and Safety of Acoustic Cluster Therapy with Modified FOLFIRINOX in Patients with Locally Advanced and Borderline Resectable Pancreatic Cancer
Erin Pierce, Ragnar Bendiksen, Amir Snapir, Alexander Raufi, Hazel Lote, Harpreet Wasan, Erkut BorazanciAbstract
Background:
Pancreatic ductal adenocarcinoma (PDAC) remains difficult to treat due to its dense stromal microenvironment, which limits drug penetration and chemotherapy efficacy. Acoustic Cluster Therapy (ACT) is an investigational ultrasound-mediated drug delivery platform designed to enhance intratumoral delivery of systemic therapy. ACT combines a proprietary intravenous formulation, PS101, containing perfluorobutane microbubbles and perfluoromethylcyclopentane microdroplets, with focused ultrasound. Following intravenous administration, ultrasound activation increases vascular permeability and enhances chemotherapy penetration. In the Phase 1 ACTIVATE trial, ACT improved chemotherapy efficacy in colorectal liver metastases, producing a 31% reduction in tumor diameter versus 5% with chemotherapy alone (Tunariu et al., 2025). Preclinical studies have also demonstrated the potential of sonochemotherapy in locally advanced PDAC (LAPC) (Han et al., 2024). ENACT evaluates ACT in patients with borderline resectable and LAPC.
Methods:
ENACT (NCT06850623) is a Phase 2, multicenter, open-label, single-arm study using a Simon's two-stage design (N=25) to evaluate ACT plus modified FOLFIRINOX (mFOLFIRINOX) in treatment-naïve patients with borderline resectable or LAPC. The primary endpoint is overall response rate per RECIST v1.1. Secondary endpoints include safety, anti-tumor activity, resection eligibility, and overall survival. Eligible patients must have confirmed PDAC, no prior treatment, disease unsuitable for curative surgery, suitability for mFOLFIRINOX, and a tumor visible on non-contrast ultrasound with a maximum depth of 14 cm.
Results:
Enrollment began in June 2025 and is ongoing at 10 sites. As of June 23, 2026, nine patients were enrolled, including five treated at PS101 60 μL/kg and four at 40 μL/kg. Across both cohorts, 112 treatment-emergent adverse events (TEAEs) were reported, most commonly gastrointestinal disorders (n=35). Sixteen TEAEs were Grade ≥3, and 11 were considered related to both chemotherapy and PS101. No suspected unexpected serious adverse reactions were reported. Seven treatment-emergent serious adverse events occurred, all unrelated to PS101 or the investigational device. ACT at both dose levels showed no apparent effect on the expected safety profile of mFOLFIRINOX.
Discussion:
Following review of safety data from both cohorts, the study advanced with PS101 60 μL/kg. Preliminary efficacy signals included >90% reductions in CA19-9, partial responses in two of three evaluable patients, and conversion to surgical resection in one patient. Technical feasibility assessments confirmed appropriate tumor depth, successful ACT administration, acceptable image quality, and adequate tumor coverage in all treated patients. These findings support continued evaluation of ACT as a strategy to enhance chemotherapy delivery and improve outcomes in borderline resectable or LAPC.Generative AI was used to assist with language editing of this abstract. All authors reviewed and verified the final content.
Citation Format:
Erin Pierce, Ragnar Bendiksen, Amir Snapir, Alexander Raufi, Hazel Lote, Harpreet Wasan, Erkut Borazanci. A Phase 2 Study to Investigate the Efficacy and Safety of Acoustic Cluster Therapy with Modified FOLFIRINOX in Patients with Locally Advanced and Borderline Resectable Pancreatic Cancer [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr A132.