A Study of Valemetostat (DS-3201b) in Combination With Darolutamide in Metastatic Castration Resistant Prostate Cancer (mCRPC)

NCT07244341 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: DS3201-3432025-522512-16-00
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 6

Brief Summary

This study will assess the safety and tolerability of valemetostat in combination with darolutamide in participants with Metastatic Castration Resistant Prostate Cancer (mCRPC).

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Metastatic Castration Resistant Prostate Cancer; DS-3201; Valemetostat; Darolutamide; mCRPC

Outcome Measures

Primary Outcomes (2)

• Part 1: Number of participants with Dose-Limiting Toxicities (DLTs)

  A DLT is defined as any Treatment Emergent Adverse Event (TEAE) not attributable to disease or disease-related processes, environmental factors, unrelated trauma, etc, that occurs during the DLT evaluation period (Day 1 to Day 28) and is Grade ≥3.

  Day 1 up to Day 28

• Part 1 and 2: Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE)

  TEAEs are defined as those Adverse Events (AEs) with start or worsening date during the on-treatment period (from the first dose date of trial intervention to 30 days after the last dose date of trial intervention).

  From Screening up to approximately 5 years

Secondary Outcomes (9)

• Prostate-Specific Antigen (PSA) 50 Response Rate

  From Screening up to approximately 5 years

• Prostate-Specific Antigen (PSA) 90 Response Rate

  From Screening up to approximately 5 years

• Prostate-Specific Antigen (PSA) Nadir Response Rate

  From Screening up to approximately 5 years

• Radiographic Progression-Free Survival (rPFS)

  From Screening up to approximately 5 years

• Overall Survival (OS)

  From Screening up to approximately 5 years

Study Arms (2)

Part 1 (Dose Escalation)

EXPERIMENTAL

Participants will receive valemetostat at escalating doses in combination with darolutamide.

Drug: Valemetostat; Drug: Darolutamide

Part 2 (Dose Expansion)

EXPERIMENTAL

Participants will receive valemetostat at 2 or more dose levels in combination with darolutamide.

Drug: Valemetostat; Drug: Darolutamide

Interventions

Valemetostat DRUG

Dose Escalation Part: Valemetostat will be administered at escalating doses. Dose Expansion Part: Valemetostat will be administered at 2 or more dose levels.

Also known as: DS-3201

Part 1 (Dose Escalation); Part 2 (Dose Expansion)

Darolutamide DRUG

Dose Escalation Part: Darolutamide will be administered at a standard dose. Dose Expansion Part: Darolutamide will be administered at a standard dose.

Also known as: NUBEQA

Part 1 (Dose Escalation); Part 2 (Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: The trial will enroll adult male participants (aged ≥18 years) with a confirmed diagnosis of mCRPC.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• Evidence of disease progression as per the PCWG3 modified RECIST v1.1 criteria.
• Evidence of metastatic disease as confirmed by radiographic imaging (CT, MRI, or bone scan).
• 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.
• Baseline PSA expression level of ≥2 ng/mL, according to a documented testing result.
• Prior therapy with an Androgen Receptor Pathway Inhibitors (ARPI).
• ECOG PS of 0 or 1 assessed no more than 28 days prior to enrollment.
• 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.
• 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

You may not qualify if:

• Prior treatment with any epigenetic agents including but not limited to EZH1, EZH2, EZH1/2, or PRC2 inhibitors.
• 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.
• 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.
• Uncontrolled or significant cardiovascular disease,
• 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.
• Has active or uncontrolled HBV infection.
• Has active or uncontrolled HCV infection.
• Has active or uncontrolled HIV infection.

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Bayer: collaborator

Study Sites (6)

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572-4607, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229-6028, United States

RECRUITING

Virginia Cancer Specialists (NEXT Virginia)

Fairfax, Virginia, 22031-2171, United States

RECRUITING

Kobe City Med Cen Gen Hosp.

Kobe, 650-0047, Japan

RECRUITING

Cancer Institute Hospital of JFCR

Kōtoku, 135-8550, Japan

RECRUITING

Toho University Sakura Medical Center

Sakura-shi, 285-8741, Japan

RECRUITING

MeSH Terms

Interventions

darolutamide

Central Study Contacts

Contact for Trial Information

CONTACT

908-992-6400; CTRinfo_us@daiichisankyo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 24, 2025
• Study Start: December 3, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): November 30, 2029
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (3); JP (3)