Oral EPI-7386 for Prostate Cancer

(EPI-7386 Trial)

No longer recruiting at 12 trial locations

Overseen By Karen Villaluna

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: ESSA Pharmaceuticals

Must be taking: Apalutamide, Prednisone

Must not be taking: Lutamides, Abiraterone

Disqualifiers: Chemotherapy, Brain metastasis, Cardiovascular, 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 new drug called EPI-7386 for prostate cancer. Researchers aim to determine its safety and the appropriate dosage. The study will also assess the drug's effects on cancer and its interactions with other medications. Men with metastatic prostate cancer and limited treatment options may be suitable candidates. Participants will take EPI-7386 alone or with other cancer drugs to evaluate its effectiveness. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting the study drug. Specifically, you must not have used hormonal agents, certain anti-cancer therapies, or strong inducers of CYP3A within 14 to 28 days before starting the study drug. It's best to discuss your current medications with the study team to see if any need to be stopped.

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

Researchers are conducting studies to understand the safety of EPI-7386 in humans. When used alone, EPI-7386 has proven safe and well-tolerated at doses up to 1200 mg per day, with no major safety concerns reported so far.

Researchers are also examining the safety of EPI-7386 in combination with other drugs like abiraterone acetate or apalutamide. These studies have shown that combining EPI-7386 with these drugs does not cause immediate safety issues, though more information is needed to fully understand how these combinations work in the body.

Overall, while EPI-7386 appears promising, this is its first test in humans, so its safety remains under study. The trial aims to determine the best dose that can be administered without causing unacceptable side effects. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Unlike the standard treatments for prostate cancer, which often include hormone therapies like Abiraterone Acetate and Enzalutamide, EPI-7386 offers a unique approach by specifically targeting the androgen receptor in a novel way. Researchers are excited about EPI-7386 because it acts as a potent androgen receptor inhibitor, potentially overcoming resistance seen with current therapies. Additionally, EPI-7386 is being studied both as a monotherapy and in combination with other treatments, which might enhance its effectiveness and provide more flexible treatment options for patients.

What evidence suggests that EPI-7386 might be an effective treatment for prostate cancer?

Research has shown that EPI-7386, a new drug being tested for prostate cancer, appears promising in early studies. Initial data suggest that EPI-7386 can block the androgen receptor, a protein that can help cancer grow, potentially reducing cancer activity. In this trial, participants will receive different dosages of EPI-7386, either as monotherapy or combined with other treatments like Apalutamide or Abiraterone Acetate with Prednisone. In a related study, 88% of patients who received a similar combination treatment experienced a significant drop in PSA levels, indicating reduced prostate cancer activity. This suggests that EPI-7386 might be effective, especially when used with other treatments. However, these results are early, and more research is needed to confirm its effectiveness in people. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

Men aged 18+ with castration-resistant prostate cancer (CRPC) and metastatic disease, who have had limited treatment options and progressed on certain therapies but not more than three. They must be in good physical condition (ECOG score of 0-1), have recovered from previous treatments' side effects, and show adequate organ function. Exclusions include recent use of specific drugs, prior chemotherapy for some cohorts, allergies to drug components, other cancers within the last 3 years, significant heart conditions or uncontrolled hypertension.

Inclusion Criteria

I am eligible for AAP treatment as per standard care.

I can carry out all my daily activities without help.

Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria

Exclusion Criteria

I have received a blood transfusion in the last 28 days.

I have spinal cord compression.

I haven't taken strong CYP3A inducers in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1a: Evaluate the safety and tolerability of EPI-7386 as a single agent in mCRPC patients

2 months

Dose Expansion

Phase 1b: Further evaluate the safety and tolerability of EPI-7386 in mCRPC patients

6 months

Combination Therapy

Evaluate EPI-7386 in combination with apalutamide acetate + prednisone or apalutamide in mHSPC or mCRPC patients

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EPI-7386

Trial Overview EPI-7386 is being tested both alone and in combination with other drugs like abiraterone acetate + prednisone (AAP) or apalutamide (APA). The study has two parts: Part A tests EPI-7386's safety at different doses; Part B tests it combined with AAP or APA. Researchers will monitor how EPI-7386 affects blood levels over time, its impact on prostate cancer and body substances, plus any potential interactions with other drugs.

How Is the Trial Designed?

Group I: Part B/Cohort 2c Experimental Treatment 2 Interventions

1200 mg EPI-7386 monotherapy for 12 weeks then 1200 mg EPI-7386 + 240 mg Apalutamide

Group II: Part B/Cohort 2b Experimental Treatment 2 Interventions

800 mg EPI-7386 monotherapy for 12 weeks then 800 mg EPI-7386 + 240 mg Apalutamide

Group III: Part B/Cohort 2a Experimental Treatment 2 Interventions

600 mg EPI-7386 monotherapy for 12 weeks then 600 mg EPI-7386 + 240 mg Apalutamide

Group IV: Part B/Cohort 1c Experimental Treatment 2 Interventions

1200 mg EPI-7386 + 1000 mg Abiraterone Acetate + Prednisone

Group V: Part B/Cohort 1b Experimental Treatment 2 Interventions

800 mg EPI-7386 + 1000 mg Abiraterone Acetate + Prednisone

Group VI: Part B/Cohort 1a Experimental Treatment 2 Interventions

600 mg EPI-7386 + 1000 mg Abiraterone Acetate + Prednisone

Group VII: Part A/Phase 1b: Cohort 2 Experimental Treatment 1 Intervention

600 mg EPI-7386 QD

Group VIII: Part A/Phase 1b: Cohort 1 (Completed) Experimental Treatment 1 Intervention

600 mg EPI-7386 BID

Group IX: Part A/Phase 1a: Cohort 7 (Completed) Experimental Treatment 1 Intervention

1200 mg EPI-7386

Group X: Part A/Phase 1a: Cohort 6 (Completed) Experimental Treatment 1 Intervention

800 mg EPI-7386

Group XI: Part A/Phase 1a: Cohort 5 (Completed) Experimental Treatment 1 Intervention

1000 mg EPI-7386

Group XII: Part A/Phase 1a: Cohort 4 (Completed) Experimental Treatment 1 Intervention

800 mg EPI-7386

Group XIII: Part A/Phase 1a: Cohort 3 (Completed) Experimental Treatment 1 Intervention

600 mg EPI-7386

Group XIV: Part A/Phase 1a: Cohort 2 (Completed) Experimental Treatment 1 Intervention

400 mg EPI-7386

Group XV: Part A/Phase 1a: Cohort 1 (Completed) Experimental Treatment 1 Intervention

200 mg EPI-7386

Who Is Running the Clinical Trial?

ESSA Pharmaceuticals

Lead Sponsor

Trials

3

Recruited

180+

Citations

1. urotoday.com urotoday.com/trials-in-progress/oral-epi-7386-trial/videos/mediaitem/3613-exploring-the-safety-and-efficacy-of-epi-7386-in-combination-with-enzalutamide-in-mcrpc-ronald-tutrone.html

Exploring the Safety and Efficacy of EPI-7386 in ... The conversation focuses on the phase two trial of EPI-7386 in combination with enzalutamide for treating metastatic castrate-resistant prostate ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04421222

NCT04421222 | Oral EPI-7386 in Patients with Castration- ... This is a phase I, clinical research study of EPI-7386, an investigational drug being studied as a treatment for patients with prostate cancer.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9304354/

Second generation androgen receptor antagonists and ... EPI-7386 inhibits cell proliferation across a panel of prostate cancer cell lines, including those driven by the AR variant AR-V7, can control ...

4. 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

ESMO 2024: Phase 1/2 Trial of Oral Masofaniten (EPI-7386 ... 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 ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT05075577

EPI-7386 in Combination with Enzalutamide Compared ... Across all dosing cohorts, 88% of patients achieved PSA90, 69% of patients achieved PSA90 in less than 90 days, and 63% of patients achieved PSA <0.2ng/mL.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06312670

NCT06312670 | Combining EPI-7386 With Enzalutamide ... The purpose of this study is to study the effects of EPI-7386 in combination with Enzalutamide on participants diagnosed with prostate cancer.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.179

Phase 1/2 study of EPI-7386 in combination with ... The combination of EPI-7386 with enzalutamide (enz) results in a deeper blockade of the AR pathway (per RNAseq and ChIPseq data) and greater antitumor activity.

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03598-6/fulltext

1813P Phase I/II trial of oral EPI-7386 in combination with ... With no safety concerns from cohorts 1-3, cohort 4 is currently enrolling at EPI-7386 BID + 160 mg QD Enz to evaluate optimal RP2Ds before the P2 component of ...