Veyonda (idronoxil) given in combination with low-dose radiation therapy was able to shrink metastatic lesions well outside the radiation field in about 27% of men with late-stage metastatic castration-resistant prostate cancer (mCRPC) in the DARRT-1 Phase 1 trial, updated data show.
“To our knowledge, this is the first time that anyone has been able to obtain a meaningful abscopal response rate in prostate cancer,” Graham Kelly, PhD, executive chairman and CEO of Noxopharm, which is developing the therapy, said in a press release.
Veyonda is an immuno-oncology therapy candidate, meaning that it is designed to act on both cancer cells and the immune system. Considered a radiation sensitizer, it blocks ENOX2, an enzyme involved in cancer cell survival, making cancer cells more vulnerable to the effects of chemotherapy and radiotherapy.
Veyonda also activates the innate and adaptive immune system, helping these cells survive chemotherapy and radiotherapy treatments and boosting their anti-cancer effects to eliminate the tumor cells that might have survived chemotherapy and radiotherapy.
Preclinical studies have also shown abscopal responses in animals, in which the radiation therapy not only shrank the irradiated tumors but also tumors outside the field of radiation. Latest results from the DARRT-1 trial seem to confirm these findings.
It remains unclear what the mechanisms behind abscopal effects are, but researchers believe that the radiation activates the immune system in one tumor, and immune cells then travel to attack cancers in distant regions.
Another hypothesis is that chemical signals are released from the irradiated cancer cells, activating suicide genes in non-irradiated tumors. Evidence for abscopal responses has been reported for several cancers, but prostate cancer has long been considered a tumor with low immune responsiveness.
DARRT-1 (NCT03307629) is an open-label, proof-of-concept Phase 1 trial investigating the safety and effectiveness of Veyonda in combination with low-dose radiotherapy in 25 men with mCRPC.
These people had exhausted all available treatment options, and had a life expectancy of six to eight months. They were receiving low-dose radiotherapy as palliative treatment for pain and symptom management, with little or no expectation of the therapy changing their disease course.
Veyonda was administered daily for 15 consecutive days as a suppository. One day after Veyonda initiation, these men also began receiving external beam radiotherapy, given over five days for a total dose of 20 Gray (Gy), to one or two measurable cancer lesions.
The main 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).
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. The combination had a favorable safety profile and was well tolerated.
Responses to treatment were seen in 10 of the 15 patients (67%) with available radiographic data, including nine with stable disease, and one with a partial response.
Noxopharm now reported that four of these 15 people (27%) also experienced an abscopal effect, which varied from about a 50% reduction in non-irradiated lesions to almost complete resolution of these lesions.
“Prostate cancer has developed a reputation as a cancer with poor immune responsiveness, but this outcome suggests that this isn’t the case when a drug with the appropriate effect on the immune system is used,” Kelly said.
“Today’s result positions Veyonda at the forefront of this emerging area of oncology and suggests that we have an exciting new prospective treatment for end-stage prostate cancer,” he added.