Evaluating the effectiveness and safety of new antiandrogen SHR3680 in patients with metastatic castration-resistant prostate cancer.

This study investigated the effectiveness and safety of a new hormonal therapy, SHR3680 (rezvilutamide), for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The study showed that SHR680 was well tolerated and had promising effectiveness in these patients.

Metastatic castration-resistant prostate cancer (mCRPC) refers to a cancer that has progressed and spread beyond the prostate gland and is no longer responsive to hormonal therapy. Patients with mCRPC are commonly treated with a type of hormonal therapy called androgen receptor-targeting agents (ARTAs) such as enzalutamide (Xtandi) and apalutamide (Erleada). These drugs block the action of androgens such as testosterone (male sex hormone that fuels prostate cancer cells' growth and spread) in prostate cancer cells.

These drugs are effective in treating mCRPC. However, a main safety problem with these medications is the risk of brain side effects such as seizures. SHR3680 is a new ARTA being developed that reaches the brain less compared to the older drugs available. However, the safety and effectiveness of SHR3680 in patients with mCRPC are still not known. 

The study involved 197 patients with mCRPC, who were not previously treated with ARTAs. There were 2 parts to the study. Part 1 included 18 patients who received SHR3680 tablets with a starting daily dose of 40 mg. This dose was then increased up to 480 mg per day. Part 2 included 179 patients, who received a daily dose of 80 mg, 160 mg, or 240 mg of SHR3680 tablets. Patients were followed up for an average of 19.2 months.

58.9% of patients experienced treatment-related side effects. The most common side effects were increased levels of proteins in the urine (13.7%), hot flushes (11.2%), and low white blood cell counts (9.6%).

After 12 weeks, 68% of patients had a prostate-specific antigen (PSA) response. PSA is a protein in the prostate that increases in prostate cancer. A PSA response is defined as a reduction of 50% or more of PSA levels as a response to treatment. 34.4% of patients achieved a reduction in prostate cancer size on images. Of these, 4.9% had a disappearance of prostate cancer. After 12 weeks, 88.3% of patients had stable disease (the cancer did not grow or spread) on bone scans. 

The study concluded that SHR3680 was safe and well tolerated and had promising effectiveness in patients with mCRPC.

This is a phase 1/2 study with a small sample size and a short follow-up period. There was also no comparison group. Further studies with large sample size and longer follow-up periods are required to validate the conclusions. This study was funded by Jiangsu Hengrui Pharmaceuticals, the manufacturer of SHR3680.