Noxopharm Ltd (ASX:NOX) has had the first patients enrolled in the US in a multi-national DARRT-2 Phase 2 clinical trial testing potential ground-breaking immunotherapy involving Veyonda® and low-dose external beam radiotherapy.
DARRT (Direct and Abscopal Response to Radiotherapy) is an experimental immunotherapy cancer treatment based on the concept of Veyonda® combining with well-tolerated, low dosage of external beam radiotherapy to trigger an immune response.
This leads to the resolution of some or all tumours in the body with the form of immune response known as an abscopal response.
Potential to revolutionise treatment
Noxopharm believes that DARRT-treatment has the potential to revolutionise cancer treatment by achieving cancer reduction through the abscopal response without many of the unwanted side effects, cost limitations and logistical challenges associated with other immunotherapies.
The DARRT-2 work builds on the success of DARRT-1 with more intense Veyonda® treatment and the company expects to receive interim data in 2022.
With low-dose (palliative) radiotherapy being a common form of therapy used in cancer care, the therapeutic and commercial opportunities of adding Veyonda to transform symptomatic relief into a meaningful tumour response are substantial.
The company is confident of securing the value of this opportunity by patents, starting with the allowance of claims in September 2021 by the US Patent Office. The FDA earlier this year granted an IND approval for the DARRT trial treatment.
US first in clinical trial
DARRT-2 is being undertaken across multiple sites in North America, Europe and Australia involving approximately 100 patients with metastatic cancers (prostate, breast, lung) who are eligible for palliative radiotherapy.
Inaugural sites in the US are the prestigious Beverly Hills Cancer Center in Los Angeles and the University of Texas’s MD Anderson Cancer Center, one of the largest cancer treatment centres in the world and consistently rated one of the best cancer treatment centres in the US.
Noxopharm chief medical officer Dr Gisela Mautner said, “The participation of prestigious institutions with their highly experienced radiation and medical oncologists is testament to the interest in and potential of the DARRT-treatment.
“More sites will come online progressively over the next few months and accelerate patient recruitment. We will keep the market updated as the study progresses.”
This work joins IONIC-1 and the soon to start CEP-2 trial as proof-of-concept trials designed to position Veyonda® as a standard means of enhancing the effectiveness of the most common forms of cancer treatments.
DARRT – how it works
DARRT involves the application of low-dose (up to 25 Gy) external beam radiotherapy in 1-5 fractionated doses to a single tumour in a single treatment cycle.
Veyonda is administered daily for up to 14 days in conjunction with the single radiotherapy cycle, and then in repeated monthly cycles without radiotherapy.
DARRT-2 builds on the encouraging safety and efficacy data from DARRT-1 but expanding into higher dosages of Veyonda (potentially up to 2400 mg daily), repeat cycles of Veyonda and three different cancer types - prostate, breast and lung.
Endpoints will be safety and tolerability, as well as clinical measures of efficacy such as tumour size changes, time until disease progression, health-related quality of life measurements, and overall survival.
The aim of DARRT is to use idronoxil, the active ingredient in Veyonda, (i) to augment radiation-induced damage of both nuclear and mitochondrial DNA damage, and (ii) to prevent repair of that damaged DNA, thereby triggering an interferon-led local immune response that becomes systemic.
About Veyonda®
Noxopharm is an Australian clinical-stage drug development company focused on the treatment of cancer and cytokine release syndrome (septic shock).
Veyonda®, the company’s first pipeline drug candidate, has two main drug actions – a moderating effect on the ceramide/sphingosine-1-phosphate balance and inhibition of STING/TBK1 signalling.
Activity against the former target contributes to its dual-acting oncotoxic and immunomodulatory functions designed to enhance the effectiveness and safety of standard oncology treatments, ie, chemotherapies, radiation therapies and immune checkpoint inhibitors.
Activity against the latter target provides an anti-inflammatory effect, as well as contributing to an anti-cancer action, but also potentially blocking septic shock.