Clinical trial evaluates a new way to target prostate cancer
A Yale-led clinical trial has reported encouraging early results for bavdegalutamide, an experimental treatment for metastatic castration-resistant prostate cancer, or mCRPC. The phase 1/phase 2 study involved patients whose cancer had already been treated and continued to grow despite testosterone-lowering therapy.
mCRPC is the advanced form of prostate cancer in which disease growth persists even when testosterone is limited. Standard hormone-directed treatments can slow cancer for a period, but resistance remains a major clinical challenge. Daniel Petrylak, a Yale School of Medicine professor and the study’s senior author, described bavdegalutamide as the first drug of its kind to be clinically tested for prostate cancer.
Using the cell’s disposal machinery
Bavdegalutamide belongs to a class of medicines known as PROTACs, short for proteolysis-targeting chimeras. Instead of only blocking a protein’s action, PROTACs are designed to use the cell’s natural protein-recycling process to degrade a target protein.
In this case, the target is the androgen receptor. Testosterone signals through that receptor, which helps control prostate-cancer growth. The drug is designed to accelerate the removal of those receptors, potentially bypassing resistance that can limit other hormone therapies.
PROTAC technology was pioneered in part by Yale researcher Craig Crews. The source notes that a PROTAC has already received U.S. Food and Drug Administration approval for use in breast cancer, while bavdegalutamide is the first androgen-receptor degrader of its type to enter clinical testing for prostate cancer.
Early-stage results
In the phase 1 portion of the study, researchers identified a daily 420-milligram dose as safe for patients who had already received treatment for mCRPC. The phase 2 portion assessed evidence of effectiveness, including changes in prostate-specific antigen, or PSA, a marker used in monitoring the disease.
The trial also evaluated tumor activity and pain. According to the Yale report, the treatment showed promise in reducing tumor activity and pain in patients with metastatic disease. The findings were published October 9 in the Journal of Clinical Oncology.
These results are early clinical evidence, rather than confirmation of a new standard treatment. Phase 1 and phase 2 studies are designed primarily to establish safety, dosing and preliminary signs of activity. Larger studies are generally needed to determine how a therapy compares with existing options and which patients may benefit most.
What the result could mean
The study nonetheless highlights a distinct therapeutic strategy: removing a cancer-driving receptor rather than merely inhibiting it. That difference may be relevant in cancers that adapt to conventional hormone therapies. For patients with mCRPC, whose disease is described in the report as incurable and lethal, a therapy that can work through a different biological mechanism could expand the set of approaches available for investigation.
The next steps for bavdegalutamide will depend on continued clinical testing. The currently reported data support further study, but they do not establish broad efficacy or regulatory approval. For now, the trial offers an early indication that targeted protein degradation can be applied to the androgen receptor in heavily pretreated metastatic prostate cancer.
This article is based on reporting by Medical Xpress. Read the original article.
Originally published on medicalxpress.com
