Valemetostat plus darolutamide for metastatic castration‑resistant prostate cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 1 interventional trial gives participants with metastatic castration‑resistant prostate cancer a combination of valemetostat (an EZH1/2 inhibitor) and the androgen‑receptor blocker darolutamide to determine safety and tolerability. Eligible men must have histologically confirmed prostate adenocarcinoma (neuroendocrine differentiation allowed except pure small‑cell), radiographic evidence of metastatic disease, and documented progression per PCWG3‑modified RECIST while on ongoing androgen‑deprivation therapy. The study will monitor adverse events, laboratory tests, and clinical assessments to define a tolerable dose and schedule for the combination and may include serial imaging and PSA measurements to look for preliminary signals of activity. As an early‑phase trial, its primary aim is safety rather than proving clinical benefit.

Why it matters

Who can join: the full rules

Key Inclusion Criteria:

The clinical site will screen for the full inclusion criteria per protocol.

1. Adult males ≥18 years of age at the time the ICF is signed (Please follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old).
2. Histologically confirmed adenocarcinoma of the prostate. Cases exhibiting neuroendocrine differentiation are eligible for enrollment, except those with a diagnosis of pure small cell carcinoma, which is excluded.
3. Evidence of disease progression as per the PCWG3 modified RECIST v1.1 criteria.
4. Evidence of metastatic disease as confirmed by radiographic imaging (CT, MRI, or bone scan).
5. Ongoing androgen deprivation at time of enrollment.

   • For participants currently being treated with luteinizing hormone-releasing hormone agonists or antagonists, therapy must have been initiated at least 4 weeks prior to enrollment and treatment must be continued throughout the trial.
6. Baseline PSA expression level of ≥2 ng/mL, according to a documented testing result.
7. Prior therapy with an Androgen Receptor Pathway Inhibitors (ARPI).
8. ECOG PS of 0 or 1 assessed no more than 28 days prior to enrollment.
9. Is willing and able to provide adequate fresh or archival tumor samples with sufficient quantity and tissue quality. A mandatory newly obtained pretreatment biopsy is required, if not clinically contraindicated and at an acceptable risk as determined by the investigator. If newly obtained tissue samples are not possible to obtain, archival tissue obtained from a lesion not previously irradiated and collected after the most recent prior therapy is acceptable.
10. A male participant capable of producing sperm is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate each trial intervention. The length of time required to continue contraception after the last dose for each trial intervention is 3 months.

    * Must not freeze or donate sperm starting at screening and throughout the Treatment Period, and for at least 3 months after the final trial intervention administration.

Note: Preservation of sperm should be considered before enrollment in this trial.

• Adhere to either of the following contraception methods:

* True abstinence from penile-vaginal intercourse, when this is in line with the preferred and usual lifestyle of the participant, OR
* Uses a penile/external condom when having penile-vaginal intercourse with an NPOCBP, PLUS partner use of an additional contraceptive method, as a condom may break or leak Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials. If the contraception requirements in the local label for any trial interventions are more stringent than those above, the local label requirements are to be followed.

Key Exclusion Criteria:

The clinical site will screen for the full exclusion criteria per protocol.

1. Prior treatment with any epigenetic agents including but not limited to EZH1, EZH2, EZH1/2, or PRC2 inhibitors.
2. Has a super scan as seen in the baseline bone scan. A super scan is defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan, such that the presence of additional metastases in the future could not be evaluated.
3. Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
4. Uncontrolled or significant cardiovascular disease,
5. Prior malignancy, active within the previous 3 years except for locally curable cancers that have been apparently cured or successfully resected, such as basal or squamous cell carcinoma, superficial bladder cancer, carcinoma in situ of the stomach, or carcinoma in situ of the breast.
6. Has active or uncontrolled HBV infection.
7. Has active or uncontrolled HCV infection.
8. Has active or uncontrolled HIV infection.

Where it's running

• University of California San Diego Moores Cancer Center
  La Jolla, California, United States Recruiting
• Beth Isreal Deaconess Medical Center
  Boston, Massachusetts, United States Recruiting
• Dana Farber Cancer Institute
  Newton, Massachusetts, United States Recruiting
• Cancer & Hematology Center
  Grand Rapids, Michigan, United States Recruiting
• Northwell Health Cancer Institute (START NY)
  Lake Success, New York, United States Recruiting
• Carolina Urologic Research Center
  Myrtle Beach, South Carolina, United States Recruiting

Study contacts

• Study coordinator: Contact for Trial Information
• Email: CTRinfo_us@daiichisankyo.com
• Phone: 908-992-6400

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• SRT-017 radioligand therapy in PSMA-positive metastatic castration-resistant prostate cancer

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• Rinzimetostat plus darolutamide in metastatic castration-resistant prostate cancer after abiraterone failure

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• FX-111 safety and pharmacokinetics in metastatic castration-resistant prostate cancer

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• Docetaxel and SX-682 in head and neck cancers and prostate cancer

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• Dual-target PSMA/PSCA CAR-NK Therapy in Advanced Prostate Cancer

  This trial tests ETB-DualNK-01, a dual-target CAR-NK cell therapy, in adults with metastatic castration-resistant prostate cancer to see if it is safe and shows early signs of activity.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.