ZEN003694 Continuation for Prostate Cancer

Enrolling by invitation at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Zenith Epigenetics

Must be taking: ZEN003694

Disqualifiers: Other trials, New therapies, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called ZEN003694, combined with enzalutamide, to determine its continued effectiveness for prostate cancer patients. The main goal is to allow patients who benefited from ZEN003694 in a previous study to continue its use. This trial targets those who completed an earlier ZEN003694 trial and found it beneficial, provided they are in good physical health as assessed by their doctor. The trial will evaluate if the combination remains safe and effective for these patients. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but it does not allow changes to your current treatment for the cancer being studied.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of ZEN003694 and enzalutamide is generally well-tolerated. In a study with prostate cancer patients, researchers found this treatment to be safe. Some patients experienced side effects, but these were manageable.

One study shared early safety results, indicating that patients with advanced prostate cancer could handle the treatment well. While some patients had side effects, they were not severe enough to outweigh the potential benefits.

Overall, existing studies suggest that this combination treatment is safe for humans, with side effects typical for this type of cancer treatment. However, as with any treatment, discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ZEN003694 because it offers a unique approach to treating prostate cancer. Unlike many standard treatments that primarily focus on reducing testosterone levels or blocking its effects, ZEN003694 works by targeting the BET proteins, which play a critical role in cancer cell growth and survival. When combined with enzalutamide, a well-known androgen receptor inhibitor, this treatment has the potential to more effectively disrupt the cancer's growth pathways. This combination could enhance treatment efficacy and provide new hope for patients who have already seen benefits from initial therapies.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that combining ZEN003694 with enzalutamide may benefit patients with advanced prostate cancer that has spread and no longer responds to standard hormone treatments. In this trial, participants will receive this combination treatment. Studies have found that this combination is manageable for patients and might work well for those who have stopped responding to other therapies. Specifically, patients in those studies have seen health improvements with this treatment. The combination targets specific pathways of cancer growth. Early results suggest this could be a promising option for those with advanced prostate cancer. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for prostate cancer patients who saw benefits from a previous ZEN003694 study. They should be in good physical condition (ECOG status of 0 or 1) and have handled the drug well before. Participants must start this follow-up within two weeks after their last dose in the original trial, unless given more time by the sponsor.

Inclusion Criteria

ECOG performance status of 0 or 1

Protocol-defined completion in a parent ZEN003694 trial

Patient has clinical benefit as determined by the investigator at the time of entry to the continuation protocol

Exclusion Criteria

Concurrent participation in another clinical investigational treatment trial

Require addition of or change to a new concomitant therapy to adequately treat the malignancy under study

Discontinued ZEN003694 or withdrew consent to participate in original Zenith Epigenetics-sponsored ZEN003694 study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Continuation Treatment

Participants continue to receive ZEN003694 in combination with enzalutamide after completing the parent protocol

Follow-up

Participants are monitored for safety and effectiveness after continuation treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• ZEN003694

Trial Overview The study continues treatment with ZEN003694 for those who benefited previously, alongside Enzalutamide, an established prostate cancer medication. The aim is to see if ongoing treatment maintains or improves patient outcomes.

How Is the Trial Designed?

Group I: Experimental: ZEN003694 in Combination with Enzalutamide Experimental Treatment 2 Interventions

Patients who have completed participation in their original ZEN003694-002 protocol and have clinical benefit as determined by the investigator may continue to receive treatment with ZEN003694 in combination with enzalutamide

Who Is Running the Clinical Trial?

Zenith Epigenetics

Lead Sponsor

Trials

10

Recruited

590+

Published Research Related to This Trial

In the SPARTAN study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved health-related quality of life (HRQoL) compared to placebo, with patients maintaining better scores over time.

Patients receiving apalutamide experienced minimal side effects and reported no worsening of fatigue, while those on placebo showed a decline in quality of life after about one year, highlighting the efficacy and tolerability of apalutamide in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Oudard, S., Hadaschik, B., Saad, F., et al.[2022]

In a phase 3 trial involving 1199 men with castration-resistant prostate cancer, enzalutamide significantly improved overall survival compared to placebo, with a median survival of 18.4 months versus 13.6 months.

Enzalutamide also showed superior efficacy in secondary outcomes, including a 54% reduction in PSA levels and improved quality of life, although it was associated with higher rates of fatigue and other side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival with enzalutamide in prostate cancer after chemotherapy. Scher, HI., Fizazi, K., Saad, F., et al.[2022]

In a phase 3 study with 1150 patients, enzalutamide combined with androgen deprivation therapy (ADT) significantly delayed the time to first confirmed clinically meaningful deterioration in pain and health-related quality of life (HRQoL) compared to ADT alone.

Specific subgroups, such as those with prior radiotherapy or low baseline HRQoL, experienced notable benefits, with enzalutamide delaying the worsening of pain and maintaining high HRQoL scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of enzalutamide on quality of life in men with metastatic hormone-sensitive prostate cancer based on prior therapy, risk, and symptom subgroups. Stenzl, A., Szmulewitz, RZ., Petrylak, D., et al.[2022]

MDV3100, an androgen receptor antagonist, has been shown to improve survival in men with metastatic castration-resistant prostate cancer who have previously undergone docetaxel chemotherapy, indicating its efficacy in this patient population.

While comprehensive safety and efficacy data are still pending, MDV3100 is considered a well-tolerated option that could complement existing treatments for advanced prostate cancer, alongside other novel therapies like abiraterone and cabazitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDV3100 for the treatment of prostate cancer. Mukherji, D., Pezaro, CJ., De-Bono, JS.[2021]

In the PROSPER trial involving 1401 patients with non-metastatic, castration-resistant prostate cancer, enzalutamide significantly improved metastasis-free survival compared to placebo, indicating its efficacy as a treatment option.

Patients receiving enzalutamide experienced longer times to clinically meaningful pain progression and symptom worsening, while maintaining a high quality of life, suggesting that enzalutamide not only prolongs survival but also enhances overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial. Tombal, B., Saad, F., Penson, D., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32694156/

A Phase Ib/IIa Study of the Pan-BET Inhibitor ZEN-3694 in ... ZEN-3694 plus enzalutamide demonstrated acceptable tolerability and potential efficacy in patients with ASI-resistant mCRPC.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04986423?term=AREA%5BBasicSearch%5D(pcwg3)&rank=1

NCT04986423 | ZEN003694 and Enzalutamide Versus ... This is an open-label, randomized, Phase 2b study of ZEN003694 in combination with enzalutamide vs. enzalutamide monotherapy in patients with mCRPC who have ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)03741-3/fulltext

1404P A phase II study of ZEN-3694 (ZEN), enzalutamide ... A phase II study of ZEN-3694 (ZEN), enzalutamide (ENZ), and pembrolizumab (P) in metastatic castration resistant prostate cancer (mCRPC): Interim safety results

4. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04471974

UCSF Prostate Cancer Trial → ZEN-3694, Enzalutamide ... This phase II trial investigates how well ZEN-3694, enzalutamide, and pembrolizumab work in treating patients with castration-resistant prostate cancer.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS5123

A randomized, open-label, phase 2b study of the BET ... A randomized, open-label, phase 2b study of the BET bromodomain inhibitor (BETi) ZEN-3694 plus enzalutamide vs. enzalutamide in patients with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7572827/

A Phase 1b/2a Study of the Pan-BET Bromodomain ... The safety and efficacy of ZEN-3694 plus enzalutamide (ENZ) was evaluated in a phase 1b/2a study in metastatic castration-resistant prostate cancer (mCRPC).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04471974

Study Details | NCT04471974 | ZEN-3694, Enzalutamide, ... The purpose of this study is to find out the effects ZEN-3694, enzalutamide, and pembrolizumab on patients with metastatic castration-resistant prostate cancer ...