Noxopharm’s Veyonda (idronoxil), in combination with low-dose radiation therapy, safely halted disease progression and eased pain in men with late-stage metastatic castration-resistant prostate cancer (mCRPC), according to results from a Phase 1b clinical trial.
“This is exciting data that validates our confidence in the future of the [Veyonda-radiotherapy] treatment regimen,” Graham Kelly, PhD, Noxopharm’s executive chairman and CEO, said in a press release.
Based on these positive results, Noxopharm plans to launch a Phase 2/3 study to evaluate the combination therapy later this year, which the company “hopes will be the final step to obtaining marketing approval.”
Formerly known as NOX66, Veyonda is a type of immuno-oncology therapy, meaning that it acts on both cancer cells and the immune system. It is considered a radiation sensitizer since it blocks ENOX2, an enzyme involved in cancer cell survival. Blocking that enzyme makes these cells more vulnerable to the effects of chemotherapy and radiotherapy.
Veyonda also was shown to activate the innate immune system, the body’s first line of defense, which increases its anti-cancer effects by promoting the elimination of cancer cells that might have survived chemotherapy and radiotherapy.
In addition, preclinical studies showed that Veyonda induces an “abscopal response,” a poorly understood process in which local radiation directed at one tumor site also induces tumor shrinkage in distant, non-irradiated, metastatic lesions.
The pivotal open-label, Phase 1b clinical trial, called DARRT-1 (NCT03307629), evaluated the safety and effectiveness of escalating doses of Veyonda in combination with low-dose radiotherapy. The study had enrolled 25 men with late-stage, progressive, mCRPC.
Its primary goal is to assess the safety of the combination therapy. Secondary goals include several measures of effectiveness, including changes in tumor size (in targeted and non-targeted areas) based on radiographic scans, overall response, and changes in the levels of pain and prostate-specific antigen (PSA) — a biomarker of prostate cancer.
The participants, who had exhausted all available treatment options and had a life expectancy of six to eight months, were receiving low-dose radiotherapy as palliative treatment for pain and symptom management. They had little or no expectation of the therapy changing the disease course.
In the dose-escalating part of the study, 12 patients were randomly assigned to receive one of three doses — 400 mg, 800 mg, and 1,200 mg — of Veyonda, administered daily for 15 consecutive days as a suppository. One day after Veyonda initiation, these men also began receiving external beam radiotherapy. That was given over five days for a total dose of 20 Gy, to one or two measurable cancer lesions.
A fourth group of patients (12 men) was treated with 1,200 mg of Veyonda — the dose selected based on the first part of the study — within the same regimen. All patients were followed-up at six, 12 and 24 weeks after treatment initiation.
Results from the 16 men (64%) who completed the study — at 24 weeks of follow-up — showed that the trial met its primary and secondary goals.
Veyonda was well-tolerated, with no significant or dose-limiting toxicities. Among 15 patients with available radiographic data, 10 (66%) responded to treatment, with nine showing stable disease, and one achieving a partial response, with a reduction of at least 30% in tumor size. Five patients had signs of disease progression.
“A 66% response rate is a substantial response rate for such late-stage disease, putting [Veyonda plus radiotherapy] right at the top end of response rates in late-stage cancer,” Kelly said.
In addition, among the 16 patients with available data on pain and PSA levels, 10 (62%) reported reductions of 43%–100% in pain levels, while five (31%) had at least a 60% drop in PSA levels.
The combination of Veyonda and low-dose radiotherapy resulted in “a very meaningful anti-cancer effect in a high proportion of men, halting progression of their disease and providing an average 80% reduction in their pain levels, including some men becoming pain-free,” Kelly added.
He also noted that the therapy’s positive safety profile is very relevant for men with advanced prostate cancer, who have generally poor health.
“Another positive is that [Veyonda plus radiotherapy] uses external beam radiotherapy, a relatively inexpensive and readily-available source of radiotherapy around the world, supporting wide uptake,” Kelly concluded.
Noxopharm expects to receive the trial’s final data, including detailed information on tumor reductions in targeted and non-targeted lesions, by March 2020.
In the upcoming Phase 2/3 clinical trial, now in the planning stages, the company intends to evaluate the therapeutic effects of six cycles of Veyonda — instead of the single cycle used in this study — combined with low-dose radiotherapy, as they believe it may improve patients’ response.
“The company anticipates that this could provide an additional anti-cancer effect and with it, the potential for an increase in the all-important overall survival endpoint,” according to the press release. Noxopharm hopes the results from this future trial will support Veyonda’s approval by regulatory agencies.
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