Acoustic Cluster Therapy Shows Benefit in Colorectal Liver Metastases

Acoustic cluster therapy plus chemotherapy led to greater tumor shrinkage than chemotherapy alone in a phase 1 trial for colorectal liver metastases.

The addition of acoustic cluster therapy to chemotherapy showed added benefit over chemotherapy alone in hard-to-treat patients with liver metastases of colorectal origin in the phase 1 ACTIVATE trial, according to a news release from Exact Therapeutics.

Tumor shrinkage was greater with acoustic cluster therapy plus chemotherapy, reducing by 29% in diameter, compared with chemotherapy alone with a 7% reduction in the same patient population, all of whom responded to chemotherapy.

"I am excited about the data from the ACTIVATE trial, which yet again underscore the attractive therapeutic proposition from our proprietary [acoustic cluster therapy] technology,” Per Walday, CEO of Exact Therapeutics, said in the news release. “The strength of the response to treatment, the safety profile and its non-invasive nature points to a unique and highly differentiated therapeutic regimen. We continue our efforts to bring [acoustic cluster therapy] to [patients with cancer] as fast as possible. 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."

In addition, acoustic cluster therapy using the proprietary agent PS101 showed a clear dose-response relationship, meaning higher doses were linked to greater therapeutic effects.

Patients receiving 40 microliters per kilogram (µl/kg) of PS101 had significantly greater tumor shrinkage than those given 20 µl/kg. Among patients responding to chemotherapy in control lesions, three of four treated with 40 µl/kg of PS101 had tumors shrink more than 30% in diameter. Overall, six of nine patients receiving acoustic cluster therapy with chemotherapy showed tumor shrinkage. PS101 was safe and well tolerated with chemotherapy.

According to the release, these positive results proved the proof of principle for the clinical application of acoustic cluster therapy technology and offer support for initiating the phase 2 ENACT study in pancreatic cancer.

Trial data is planned to be published and presented at future medical conferences.

What is Acoustic Cluster Therapy, and What Does it Mean?

Acoustic Cluster Therapy uses PS101, given intravenously (through the vein) and activated by ultrasound over a target area. PS101 contains tiny clusters of gas microbubbles and microdroplets, and high-frequency ultrasound causes these to form larger bubbles that temporarily block capillaries. Then, low-frequency ultrasound makes the bubbles oscillate, improving delivery of chemotherapy to the targeted tissue.

According to the trial’s clinicaltrials.gov listing, PS101-mediated acoustic cluster therapy may enhance the delivery of an anticancer agent to the ultrasound-targeted area. Preclinical studies suggest it could provide meaningful benefit without significant added toxicity.

Phase 1 ACTIVATE Trial in Colorectal Liver Metastases

ACTIVATE is a phase 1, multi-center trial testing the safety, tolerability and early anti-cancer effects of acoustic cluster therapy combined with chemotherapy (FOLFOX or FOLFIRI) in patients with colorectal liver metastases. As per the news release, each patient serves as their own control by comparing tumor response in acoustic cluster therapy-treated lesions versus chemotherapy-only lesions. Response was evaluated at week eight by blinded central review. The trial enrolled 11 difficult-to-treat patients in the UK, with 9 being evaluable.

Depending on the phase 1 results, the study may expand to include patients with liver metastases from colorectal and pancreatic cancer.

"Today's update marks the successful completion of the ACTIVATE trial,” chief medical officer of Exact Therapeutics, Amir Snapir said in the news release. “The results give us great confidence in the treatment potential of the [acute cluster therapy] technology for patients with solid tumors."

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