Key Takeaways
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- The five-year survival rate for men with metastatic prostate cancer is just 34%.
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A new medication called BMS-986365 is a next-generation therapy designed to block and break down the androgen receptor, a key driver of prostate cancer growth.
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In an early clinical trial, BMS-986365 showed promising results for men with advanced prostate cancer. In this study, BMS-986365 will be compared to current treatments.
September is Prostate Cancer Awareness Month, a time to highlight the progress being made in treating the disease, as well as the challenges that remain. Thanks to new therapies developed over the past two decades, men diagnosed with prostate cancer are living longer and with a better quality of life.
For those whose cancer is found early and has not spread, survival rates are excellent and even patients with metastatic disease can survive for many years. This is a dramatic improvement from past decades.
What if prostate cancer spreads?
Once the disease spreads (metastasizes) to other parts of the body, such as bones and lymph nodes, initial treatment is based on lowering the male hormone testosterone along with blocking the androgen receptor (the protein the cancer cells use to absorb and process testosterone).
These treatments have a greater likelihood of knocking down prostate cancer, but the cancer can return or progress despite initial success.
Eventually, metastatic prostate cancer becomes castrate-resistant prostate cancer (mCRPC), where the cancer cells persist and grow, even when they’re deprived of testosterone. Nearly all prostate cancer-related deaths occur after the disease reaches this stage. Although some individuals can live 10 or even 20 years with other types of metastatic cancer, the five-year survival rate for men with metastatic prostate cancer is just 34%.
That’s why researchers are evaluating a new medication called BMS-986365. This next-generation therapy is designed to block and break down the androgen receptor, a key driver of prostate cancer growth.
Providence Cancer Institute is offering this clinical trial to men with mCRPC who have already been treated with standard therapies but need new options.
BMS-986365 will be compared to investigator's choice of therapy (called an active comparator), which includes:
- Docetaxel plus prednisone/prednisolone or
- Abiraterone plus prednisone/prednisolone or enzalutamide.
How BMS-986365 differs from standard therapies
BMS-986365 takes a dual approach by blocking and breaking down the androgen receptor. This approach helps prevent cancer cells from turning on genes that fuel tumor growth. Applying a two-in-one strategy is important because prostate tumors eventually develop resistance to hormone therapies.
In an early clinical trial, BMS-986365 showed promising results for men with advanced cancer who had already received prior treatments. The medication produced clinical benefits, radiographic regression (improvement on scans or x-rays) and biochemical responses (decreased PSA levels), regardless of whether tumors had changes in the androgen receptor. Men who had previously taken hormone-targeting medications but hadn’t yet received chemotherapy tended to stay on treatment longer without their cancer progressing.
In this current study, comparing BMS-986365 to current treatments will allow researchers to evaluate its ability to extend survival and improve quality of life for men with prostate cancer.
What are current standard therapies for mCRPC?
Once castration-resistant prostate cancer has developed, the primary goal of treatment is to relieve symptoms and slow the growth of cancer.
Androgen deprivation therapy is a standard hormone treatment for men with metastatic prostate cancer. But patients with mCRPC might also receive:
- Androgen receptor pathway inhibitors (ARPIs): Medications such as abiraterone and enzalutamide block androgen receptors and reduce hormone production. Abiraterone and enzalutamide were the first and only ARPIs to receive approval for treating mCRPC and have been the first-line standards of care in patients with mCRPC. These are approved as pre- and post- chemotherapy therapies.
- Chemotherapy: Docetaxel (and cabazitaxel) are used when the disease progresses quickly or causes severe symptoms.
- Radiation treatment: This therapy targets cancer that has spread to the bones or lymph node sites.
- Immunotherapy: Medicines that boost immune activity can be offered to select prostate cancer patients. Options include sipuleucel-T (a personalized vaccine made from the patient’s immune cells) or pembrolizumab (antibody targeting PD-1 on activated immune cells). Pembrolizumab is most effective in prostate cancers that have a high tumor mutational burden (TMB) or that have microsatellite instability (MSI). TMB and MSI can be determined from a previous biopsy specimen of the prostate or sometimes with a blood test (liquid biopsy).
- PARP inhibitors: About 20% of prostate cancers have mutations in homologous recombinant repair (HRR) genes that influence the poly-ADP ribose polymerase (PARP) enzyme. Some examples of HRR genes include BRCA1, BRCA2 and ATM.
- Lu-177-PSMA (Pluvicto): This agent targets prostate-specific membrane antigen (PSMA), which is distinct from PSA. Most prostate cancers express PSMA. This medicine works by sticking to cells that have PSMA and delivering a small dose of radiation to those cells. It can be used after ARPI therapy and/or chemotherapy.
Study design and duration
The two-part study currently enrolling patients at Providence Cancer Institute has multiple arms. In Part 1, study participants are randomized equally to two BMS-986365 dose levels or an active comparator (investigator's choice). In Part 2, participants are randomized equally between a selected BMS-986365 dose and the active comparator.
Participants will stay on treatment until their cancer clearly progresses on scans, side effects become too severe, they choose to stop or the study ends. For those receiving chemotherapy with docetaxel, treatment is limited to a maximum of 10 cycles. The study is expected to last four years.
Providence Cancer Institute is the only center in Oregon enrolling patients in this trial. Brendan Curti, M.D., is the principal investigator.
For more information on the study, visit:
If you or someone you know is living with prostate cancer, talk with your physician about whether a clinical trial may be an option. Participating in research not only offers access to emerging therapies but also helps move science forward for others facing the same diagnosis.
To refer a patient:
- Call 503-215-1979
- Send an email
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