The COSMYC Trial (COmbined Suppression of MYC)

NCT06922318 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: J2513IRB00480365P50CA272391
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to determine if receiving the combination of testosterone and ZEN-3694 followed by the combination of enzalutamide plus ZEN-3694 will decrease the size of tumors in patients with prostate cancer that has become resistant to castration and other therapies. The investigators also want to determine if dosing first with the combination of testosterone and ZEN-3694 may cause enzalutamide and ZEN-3694 to work more effectively.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Prostate Cancer; ZEN-3694; Bipolar androgen therapy; testosterone cypionate; enzalutamide

Outcome Measures

Primary Outcomes (2)

• Clinical/radiographic progression free survival (PFS) with BATZEN

  Median time from the first date of BATZEN to the date of first documented radiological progression per RECIST 1.1 for soft tissue or per Prostate Cancer Working Group 3 (PCWG3) for bone lesions, the development of symptoms or complications attributable to cancer progression, or death, whichever occurs first.

  2 years

• Prostate specific antigen (PSA)-Progression free survival (PFS) with ZENZA

  PSA-PFS on ZENZA is the median time from start of ZENZA to time of PSA progression according to PCWG3 criteria ,or censored at the last date of PSA assessment for patients without PSA progression.

  2 years

Secondary Outcomes (9)

• Number of participants with PSA 50 (≥50% PSA reduction) response to BATZEN

  2 years

• Number of participants with PSA50 response to ZENZA

  2 years

• Time to PSA progression while on BATZEN

  2 years

• Number of participants with Objective response to BATZEN and ZENZA, respectively per RECIST 1.1 criteria

  2 years

• Progression Free Survival (PFS2) (PSA progression on ZENZA)

  2 years

Study Arms (2)

BATZEN

EXPERIMENTAL

ZEN-3694 48 mg (one 48 mg tablet) will be taken once per day by mouth each cycle (each cycle is 28 days). On the first day of each cycle, testosterone cypionate (400 mg) injection will be administered into the buttocks. The participant will continue with additional 28-day cycles of ZEN-3694 pills and testosterone injections until there is disease progression on bone and CT scans.

Drug: ZEN-3694; Drug: Testosterone cypionate; Drug: Luteinizing hormone-releasing hormone (LHRH) analogue

ZENZA

EXPERIMENTAL

ZENZA cycles will begin once there is disease progression on bone and CT scans.ZEN-3694 dose will increase to 72 mg (one 48 mg and two 12 mg tablets) to be taken daily by mouth. Enzalutamide 160 mg (four 40 mg capsules) will be taken daily by mouth.

Drug: ZEN-3694; Drug: Enzalutamide; Drug: Luteinizing hormone-releasing hormone (LHRH) analogue

Interventions

ZEN-3694 DRUG

One ZEN-3694 pill (48 mg) will be taken each day of each BATZEN cycle.

BATZEN; ZENZA

Testosterone cypionate DRUG

On day 1 of each BATZEN cycle testosterone cypionate (400 mg) injection to the buttocks will be administered.

BATZEN

Enzalutamide DRUG

Enzalutamide 160 mg (four 40 mg capsules) taken daily by mouth on each ZENZA cycle.

ZENZA

Luteinizing hormone-releasing hormone (LHRH) analogue DRUG

Patients will continue on ADT with LHRH agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) or LHRH antagonist (Degarelix or Relugolix) if not surgically castrated throughout the duration of the study to inhibit endogenous testosterone production.

Also known as: Zoladex, Trelstar, Eligard, Lupron, Degarelix, Relugolix

BATZEN; ZENZA

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance status ≤2.
• Age ≥18 years.
• Histologically-confirmed adenocarcinoma of the prostate.
• Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist).
• Documented castrate level of serum testosterone (\<50 ng/dl).
• Metastatic disease radiographically documented by CT or bone scan. While CT scan is preferred, Prostate-Specific Membrane Antigen (PSMA) scan (e.g. Pylarify) may be substitute for CT scan if evidence of metastatic disease observed on the CT portion of the PSMA scan.
• Must have had disease progression while on a second-generation AR-axis inhibitor (Abiraterone, Enzalutamide, Darolutamide, or Apalutamide) based on:
• PSA progression defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart i. And/ Or Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions or PCWG3 for patients with bone disease
• Screening PSA must be ≥ 1.0 ng/mL.
• Patients with soft tissue lesion amenable to biopsy must agree to biopsy collection pre-treatment and at a defined point on treatment to perform tumor tissue analysis.
• Prior treatment with Provenge vaccine, 223 Radium (Xofigo), poly(ADP-ribose) polymerase (PARP) inhibitors, taxane chemotherapy, Pluvicto, antiandrogens (including enzalutamide, darolutamide, and apalutamide), and radiation is allowed if \>4 weeks from last dose.
• Prior treatment with BAT is allowed if the patient has progressed on an AR-axis inhibitor (i.e. abiraterone or antiandrogen) since BAT treatment.
• Patients must be withdrawn from second-generation AR-axis inhibitor (Abiraterone, Enzalutamide, Darolutamide, or Apalutamide) for ≥ 2 weeks.
• Attempts must be made to wean patients off prednisone prior to starting therapy. Patients who cannot be weaned due to symptoms may continue on lowest dose of prednisone achieved during weaning period.
• Acceptable liver function:

You may not qualify if:

• Pain due to metastatic prostate cancer requiring treatment intervention with opioid pain medication.
• ECOG Performance status ≥3
• Requirement for urinary self-catheterization for voiding due to obstruction secondary to prostatic enlargement well documented to be due to prostate cancer or benign prostatic hyperplasia (BPH). Patients with indwelling Foley or suprapubic catheter for obstructive symptoms are eligible.
• Active uncontrolled infection. Patients with a history of HIV/AIDS may be eligible if cluster of differentiation 4 (CD4)+ T cell counts are ≥ 350 cell/ul, they have had no opportunistic infection within the past 12 months, they have been on established antiretroviral therapy (ART) for at least four weeks, the HIV viral load is less than 400 copies/ml prior to enrollment, and there is no significant drug-drug interaction with ART and the study drugs. Patients with chronic hepatitis B virus (HBV) infection with active disease who meet criteria for anti HBV therapy are eligible if they are on a suppressive antiviral therapy prior to enrollment and there is no drug-drug interaction with the study drugs. Patients with a history of HCV infection are eligible if they have completed curative antiviral treatment and the hepatitis C virus (HCV) viral load is below the limit of quantification.
• Any condition or mental impairment that may compromise the ability to give informed consent, patient's safety or compliance with study requirements as determined by the investigator.
• Patients receiving anticoagulation therapy with warfarin, rivaroxaban, or apixaban are not eligible for study. \[Patients on enoxaparin or edoxaban are eligible for study. Patients on warfarin, rivaroxaban, or apixaban, who can be transitioned to one of these alternative agents prior to starting study treatments will be eligible\].
• Patients are excluded with prior history of a thromboembolic event within the last 12 months that are not being treated with systemic anticoagulation.
• Hematocrit \>51%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure \[per Endocrine Society Clinical Practice Guidelines (34)\]
• Patients allergic to sesame seed oil or cottonseed oil are excluded.
• Major surgery (i.e. as defined by treating physician) within 3 weeks before screening, or has not fully recovered from prior surgery (i.e., unhealed wound). Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.
• Patients with history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, brain arteriovenous malformation).

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Zenith Epigenetics: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21205, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

testosterone 17 beta-cypionate; enzalutamide; Gonadotropin-Releasing Hormone; Goserelin; Triptorelin Pamoate; luprolide acetate gel depot; Leuprolide; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; relugolix

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Samuel Denmeade, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samuel Denmeade, MD

CONTACT

410-733-3232; denmesa@jhmi.edu

Sin Chan, MS

CONTACT

410-614-3630; schan44@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2025
• First Posted: April 10, 2025
• Study Start: August 19, 2025
• Primary Completion (Estimated): August 30, 2031
• Study Completion (Estimated): August 30, 2031
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)