EPI-7386 + Enzalutamide for Prostate Cancer

No longer recruiting at 26 trial locations

Overseen By Karen Villaluna

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: ESSA Pharmaceuticals

Must be taking: LHRH agonist/antagonist

Must not be taking: Biologic therapy, Chemotherapy

Disqualifiers: Seizure history, Cardiovascular disease, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new drug combination for treating advanced prostate cancer resistant to standard hormone treatments. It pairs EPI-7386, an experimental treatment, with enzalutamide to assess whether this combination can better manage the disease. The trial will first determine safe dosages, then compare the combination to enzalutamide alone. Men with prostate cancer that has spread and is not responding to typical hormone therapy might be suitable candidates for this study. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

You may need to stop certain medications before joining the trial. Specifically, you cannot use hormonal agents, herbal products, or alternative therapies with anti-tumor activity within 28 days before starting the study. Also, avoid strong inhibitors or inducers of certain enzymes (CYP2C8, CYP3A) and some other specific drugs.

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

Research has shown that the combination of EPI-7386 and enzalutamide is generally well-tolerated by patients with metastatic castration-resistant prostate cancer (mCRPC). Studies have found that this combination effectively blocks the androgen receptor pathway, which is crucial for slowing tumor growth.

Regarding safety, patients taking EPI-7386 with enzalutamide have tolerated the treatment well. No unusual side effects have been reported beyond those typically seen with prostate cancer treatments. The combination has a good safety profile, meaning any side effects are manageable and not severe.

Overall, early findings suggest that EPI-7386, when used with enzalutamide, is safe for people with mCRPC. However, more data from ongoing trials will help confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about EPI-7386 combined with Enzalutamide for prostate cancer because it targets the androgen receptor pathway, which is crucial for the growth of prostate cancer cells. Unlike standard treatments that only involve Enzalutamide, EPI-7386 adds a novel approach by acting as an androgen receptor antagonist, potentially improving the treatment's overall efficacy. Additionally, this combination aims to overcome resistance seen in some patients treated solely with Enzalutamide, offering hope for more durable responses and better outcomes.

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

This trial will evaluate the combination of EPI-7386 with Enzalutamide for prostate cancer. Studies have shown mixed results for this combination. In one study, 88% of patients taking both medications experienced a significant drop in PSA levels, which indicate prostate cancer activity. However, the same study found that Enzalutamide alone sometimes worked slightly better. EPI-7386 interferes with the AR signaling pathway, a key factor in prostate cancer growth. While the combination shows promise, not all results surpassed those of Enzalutamide alone. These mixed outcomes are important to consider when assessing the treatment's potential effectiveness. Participants in this trial will be randomized to receive either the combination of EPI-7386 and Enzalutamide or Enzalutamide alone. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread, who haven't used second-generation anti-androgens or certain other treatments recently. They must have good performance status (able to carry out daily activities) and organ function, with low testosterone levels maintained by ongoing treatment.

Inclusion Criteria

My prostate cancer is not responding to hormone therapy.

I am fully active or can carry out light work.

I have not taken second generation anti-androgens.

Exclusion Criteria

I have a serious heart condition.

I am not taking medication that is sensitive to certain liver enzymes.

I have spinal cord compression.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Single-arm dose escalation study of EPI-7386 in combination with a fixed dose of enzalutamide to evaluate safety and tolerability and establish RP2CDs

4 weeks

Multiple visits for dose escalation and monitoring

Phase 2 Treatment

Two-arm, randomized (2:1), open-label study comparing EPI-7386 + enzalutamide vs. enzalutamide alone

Until disease progression or unacceptable toxicity

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• EPI-7386

Trial Overview The trial is testing a new drug combo for advanced prostate cancer. Phase 1 checks the safety of EPI-7386 with enzalutamide at different doses. Phase 2 compares two groups: one taking both drugs and another taking only enzalutamide, based on earlier results for effectiveness without worsening disease.

How Is the Trial Designed?

Group I: Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1) Experimental Treatment 1 Intervention

RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg

Group II: Phase 1 Cohort 4 Experimental Treatment 1 Intervention

RP2D mg EPI-7386 in combination of Enzalutamide160 mg

Group III: Phase 1 Cohort 3 Experimental Treatment 1 Intervention

600 mg BID EPI-7386 in combination of Enzalutamide120 mg

Group IV: Phase 1 Cohort 2 Experimental Treatment 1 Intervention

800 mg QD EPI-7386 in combination of Enzalutamide120 mg

Group V: Phase 1 Cohort 1 Experimental Treatment 1 Intervention

600 mg QD EPI-7386 in combination of Enzalutamide120 mg

Group VI: Phase 2 Enzalutamide single agent Active Control 1 Intervention

Enzalutamide 160 mg

Enzalutamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Canada as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Japan as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Who Is Running the Clinical Trial?

ESSA Pharmaceuticals

Lead Sponsor

Trials

3

Recruited

180+

Citations

1. onclive.com onclive.com/view/essa-discontinues-phase-2-study-of-masofaniten-plus-enzalutamide-in-mcrpc

ESSA Discontinues Phase 2 Study of Masofaniten Plus ... Interim results showed a PSA90 response rate of 64% for the combination therapy versus 73% for enzalutamide monotherapy.

2. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-prostate-cancer/154810-esmo-2024-phase-1-2-trial-of-oral-masofaniten-epi-7386-in-combination-with-enzalutamide-compared-to-enzalutamide-alone-in-metastatic-castration-resistant-prostate-cancer-mcrpc-subjects.html

Phase 1/2 Trial of Oral Masofaniten (EPI-7386 ... - UroToday A total of 88% of the patients dosed with masofaniten + enzalutamide achieved a PSA decline > 90%; With a current median follow up of 15.2 months, time to event ...

3. curetoday.com curetoday.com/view/masofaniten-plus-xtandi-has-potential-clinical-benefits-for-patients-with-mcrpc

Masofaniten Plus Xtandi Has Potential Clinical Benefits for ... Masofaniten's unique mechanism of action disrupts the AR signaling pathway, the primary pathway that drives prostate cancer growth, by ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05075577

Study Details | NCT05075577 | EPI-7386 in Combination ... Study was terminated early due to a lack of improved efficacy. EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with MCRPC.

5. urologytimes.com urologytimes.com/view/masofaniten-plus-enzalutamide-shows-promise-in-mcrpc

Masofaniten plus enzalutamide shows promise in mCRPC Among patients across all 4 cohorts of the study, 88% (14/16 patients) achieved PSA50, 81% (13/16 patients) achieved PSA90, 69% (11/16 patients) ...

6. onclive.com onclive.com/view/masofaniten-plus-enzalutamide-demonstrates-safety-and-durable-responses-in-mcrpc

Masofaniten Plus Enzalutamide Demonstrates Safety and ... Masofaniten administered in combination with enzalutamide (Xtandi) was tolerable, pharmacokinetically active, and led to a decrease in prostate- ...

7. urologytimes.com urologytimes.com/view/phase-2-trial-of-masofaniten-plus-enzalutamide-in-mcrpc-has-been-terminated

Phase 2 trial of masofaniten plus enzalutamide in mCRPC ... At the time of data report, 64% of patients in the combination arm vs 73% of patients in the monotherapy arm achieved a PSA90 response. The ...

8. withpower.com withpower.com/trial/phase-2-metastatic-hormone-sensitive-prostate-cancer-mhspc-7-2024-3c35f

EPI-7386 + Enzalutamide for Prostate Cancer The purpose of this study is to study the effects of EPI-7386 in combination with Enzalutamide on participants diagnosed with prostate cancer.