Abstract 6221: First-in-human study of acoustic cluster therapy consisting of PS101 combined with chemotherapy and insonation in patients with liver metastases of colorectal cancer origin
Authors: Banerji Udai , Yau Wing , O'Leary Mark T. , Bush Nigel , Gurung Sumita , Snapir Amir , Bamber Jeff C. , Tunariu Nina 
Published: March 2024

Abstract
Background: Suboptimal delivery of anti-cancer agents to cancer tissue compromises the effectiveness of therapeutics. PS101 consists of microclusters of perfluorobutane microbubbles and perfluoromethylcyclopentane (PFMCP) microdroplets. Acoustic cluster therapy (ACT) consists of PS101 administered intravenously and insonated over a tumour with diagnostic ultrasound (2 MHz or above), which fuses the components of PS101 to form larger ACT bubbles that are temporarily trapped in capillaries, followed by low frequency (0.5 MHz) insonation, which induces oscillation of the ACT bubbles, stretching capillaries. Given concurrently with chemotherapy, this enhances delivery of chemotherapy to target tissues.
Methods: We describe a first-in-human phase1 study to evaluate the safety and tolerability, pharmacokinetics, and preliminary anti-cancer activity of ACT treatment and the chemotherapy regimens FOLFOX or FOLFIRI in patients with liver metastases of colorectal origin (NCT04021277). The dose escalation cohorts evaluated safety of 20 µL/kg and 40 µL/kg dose levels of PS101 combined with chemotherapy. The primary assessment of anti-tumor activity consisted of within-patient comparison of radiographic responses between ACT-treated lesions (insonated) and control lesions (non-insonated).
Results: We had previously treated mice bearing SW620 xenografts treated with a control arm of Irinotecan at 60 mg/kg IP or Irinotecan plus PS101 at 2ml/kg and insonation in the experimental arm and showed a difference in survival in the experimental arm 34 days Vs 54 days p &lt;0.01 (1). In the first in human clinical trial 8 patients were enrolled into the dose escalation part of the study, of which 2 subjects were not evaluable for dose escalation decision. There were no CTCAE grade 3, or above AEs or SAEs related to PS101 or the ultrasound. 4/8 patients discontinued treatment due to AEs - all related to chemotherapy. Median plasma concentration of PFMPC 5 minutes after the injection was 117 ng/ml (n=3, range 82 to 158) in the 20 µl/kg cohort and 233 ng/ml (n=4, range 217 to 275) in the 40 µl/kg cohort. 5 out of 6 patients had greater shrinkage of the insonated lesion compared with control lesions. The median percentage difference in maximum diameter of lesions between baseline and week 8 assessments, for insonated and non-insonated lesions, was -16% (range 25 to -42) and -3% (range 12 to -19), respectively. The dose expansion part of the study is ongoing, randomizing patients receiving FOLFIRI chemotherapy up to 10 patients each between 20 µl/kg and 40 µl/kg dose levels.
Conclusions: Following preclinical activity in xenograft models, the ongoing first in human study of ACT in patients with colorectal cancer has shown clinical translation of differential activity in insonated metastasis. Reference:
Reference: 1.Bush N et al Front Pharmacol 2019, 10:1299
Citation Format: Udai Banerji, Wing Yau, Mark T. O'Leary, Nigel Bush, Sumita Gurung, Amir Snapir, Jeff C. Bamber, Nina Tunariu. First-in-human study of acoustic cluster therapy consisting of PS101 combined with chemotherapy and insonation in patients with liver metastases of colorectal cancer origin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6221.