EXACT Therapeutics has announced positive final results from its Phase 1 ACTIVATE trial, demonstrating that its proprietary Acoustic Cluster Therapy (ACT) technology significantly enhances the effectiveness of standard chemotherapy in patients with colorectal liver metastases.
The clinical trial showed that among patients who responded to chemotherapy, tumors treated with ACT exhibited a significantly greater reduction in diameter compared to control tumors treated with chemotherapy alone (-29% versus -7%, p<0.05). This marked improvement in tumor shrinkage provides crucial validation for the clinical application of ACT technology.
"I am excited about the data from the ACTIVATE trial, which yet again underscore the attractive therapeutic proposition from our proprietary ACT technology," said Per Walday, CEO of EXACT Therapeutics. "The strength of the response to treatment, the safety profile and its non-invasive nature points to a unique and highly differentiated therapeutic regimen."
How ACT Technology Works
Acoustic Cluster Therapy consists of PS101, a formulation of microclusters containing perfluorobutane microbubbles and perfluoromethylcyclopentane microdroplets, administered intravenously. The treatment involves a two-step ultrasound process: high-frequency insonation causes PS101 to form larger ACT bubbles that temporarily lodge in capillaries, followed by low-frequency insonation that induces oscillation of these bubbles, enhancing delivery of concurrently administered chemotherapy to target tissues.
This innovative approach represents a potential breakthrough in targeted drug delivery, potentially applicable across multiple cancer types and other indications.
Key Findings from the ACTIVATE Trial
The trial enrolled 11 hard-to-treat patients with colorectal liver metastases, with 9 evaluable for response. The study utilized a within-patient control design, allowing direct comparison between ACT-treated lesions and non-treated lesions in the same individuals.
Key findings include:
- Tumor shrinkage was observed in 6 out of 9 patients who received ACT with chemotherapy
- A clear dose-response relationship was demonstrated, with the higher PS101 dose (40 μl/kg) showing significantly greater tumor shrinkage than the lower dose (20 μl/kg)
- In patients who responded to chemotherapy, 3 out of 4 patients receiving the higher dose (40 μl/kg) showed tumor shrinkage exceeding 30% in diameter
- PS101 was safe and well-tolerated when combined with standard chemotherapy regimens (FOLFOX or FOLFIRI)
Dr. Amir Snapir, Chief Medical Officer of EXACT Therapeutics, noted, "Today's update marks the successful completion of the ACTIVATE trial. The results give us great confidence in the treatment potential of the ACT technology for patients with solid tumours."
Implications for Difficult-to-Treat Cancers
The positive results from the ACTIVATE trial represent a significant step forward in addressing the unmet need for more effective treatments for difficult-to-treat cancers. The substantial improvement in tumor response suggests that ACT could potentially extend survival and improve quality of life for patients facing aggressive diseases like metastatic colorectal cancer and pancreatic cancer.
The confirmation of a dose-response relationship provides valuable information for optimizing treatment protocols in future studies. Moreover, the positive safety profile reinforces the potential for broader clinical application across various cancer types.
Next Steps: The ENACT Phase 2 Trial
Building on the momentum of the ACTIVATE study, EXACT Therapeutics is now preparing to initiate its Phase 2 ENACT trial in patients with locally advanced or borderline resectable pancreatic cancer—a disease with notoriously poor prognosis and limited treatment options.
"We continue our efforts to bring ACT to cancer patients as fast as possible," said Walday. "Building on the momentum of the ACTIVATE study, we are excited to be approaching the first patient dosing in our Phase 2 ENACT trial in locally advanced pancreatic cancer."
The company plans to present detailed data from the Phase 1 ACTIVATE trial in a future scientific publication and at upcoming medical conferences.
About the ACTIVATE Trial Design
ACTIVATE was designed as a multi-center, single-arm, open-label Phase 1 trial to assess the safety, tolerability, pharmacokinetics, and preliminary anti-cancer activity of ACT treatment combined with standard chemotherapy regimens (FOLFOX or FOLFIRI) in patients with liver metastases of colorectal origin.
The innovative trial design allowed each patient to serve as their own control, with primary assessment consisting of within-patient comparison of radiographic responses between ACT-treated lesions (insonated plus chemotherapy) and control lesions (chemotherapy alone, non-insonated). Assessment was conducted at week 8 by blinded central review.
EXACT Therapeutics, a clinical-stage precision medicine company utilizing ultrasound and microbubbles for targeted drug delivery in oncology, is traded on Euronext Growth Oslo (EXTX). The company expressed gratitude to the patients, their families, and the investigators for their participation and contribution to the ACTIVATE trial.
