Metastatic Castration-resistant Prostate CancerPhase 1NCT07244341
A Study of Valemetostat (DS-3201b) in Combination With Darolutamide in Metastatic Castration Resistant Prostate Cancer (mCRPC)
A Phase 1 study testing Valemetostat and Darolutamide in people with Metastatic Castration-resistant Prostate Cancer, run by Daiichi Sankyo at 29 sites in 7 countries.
Trial summary
This study will assess the safety and tolerability of valemetostat in combination with darolutamide in participants with Metastatic Castration Resistant Prostate Cancer (mCRPC). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castration-resistant Prostate Cancer
- What is being tested?
- Valemetostat and Darolutamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 29 sitesin 7 countries
- Study dates
- 3 Dec 2025to 30 Nov 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The clinical site will screen for the full inclusion criteria per protocol.
- 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.
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- 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
- 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.
Who cannot join
- The clinical site will screen for the full exclusion criteria per protocol.
- 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.
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- Has active or uncontrolled HBV infection.
- Has active or uncontrolled HCV infection.
- Has active or uncontrolled HIV infection.
Trial locations and contacts
29 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
29 sites in 7 countries
United States9 sites, 9 recruiting
- Recruiting
Beth Isreal Deaconess Medical Center
Boston, Massachusetts, 02215
- Recruiting
Virginia Cancer Specialists (NEXT Virginia)
Fairfax, Virginia, 22031
- Recruiting
Cancer & Hematology Center
Grand Rapids, Michigan, 49546-2302
- Recruiting
University of California San Diego Moores Cancer Center
La Jolla, California, 92037-0698
- Recruiting
Northwell Health Cancer Institute (START NY)
Lake Success, New York, 11042-1118
- Recruiting
Medical College Of Wisconsin
Milwaukee, Wisconsin, 53226-3522
- Recruiting
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572-4607
- Recruiting
Dana Farber Cancer Institute
Newton, Massachusetts, 02467
- Recruiting
NEXT Oncology
San Antonio, Texas, 78229-6028
China5 sites, 5 recruiting
- Recruiting
Sun Yatsen University Cancer Center
Guangzhou, 510060
- Recruiting
Fudan University Shanghai Cancer Center - Xuhui District
Shanghai, 200032
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, 200032
- Recruiting
Shanghai General Hospital
Shanghai, 200080
- Recruiting
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, 325000
Australia4 sites, 4 recruiting
- Recruiting
Box Hill Hospital
Box Hill, Victoria, 3128
- Recruiting
Chris OBrien Lifehouse
Camperdown, New South Wales, 2050
- Recruiting
Icon Cancer Centre Chermside
Chermside, Queensland, 4032
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Japan4 sites, 4 recruiting
- Recruiting
National Cancer Center Hospital East
Kashiwa-shi, 277-8577
- Recruiting
Kobe City Med Cen Gen Hosp.
Kobe, 650-0047
- Recruiting
Cancer Institute Hospital of JFCR
Kōtoku, 135-8550
- Recruiting
Toho University Sakura Medical Center
Sakura-shi, 285-8741
Spain4 sites, 4 recruiting
- Recruiting
Hospital Quironsalud Barcelona
Barcelona, 08023
- Recruiting
Hospital San Pedro
Logroño, La Rioja, 26006
- Recruiting
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
- Recruiting
Hospital Universitario Quironsalud Madrid
Pozuelo de Alarcón, Madrid, 28223
France2 sites, 2 recruiting
- Recruiting
Centre Oscar Lambret
Lille, Nord, 59020
- Recruiting
Centre Leon Berard
Lyon, Rhone, 69008
Ireland1 site, 1 recruiting
- Recruiting
Mater Misericordiae University Hospital
Dublin, D07 R2WY
About this study
Official title: A Phase 1, Multicenter Trial Evaluating the Safety, Tolerability, and Efficacy of Valemetostat (DS-3201) in Combination With Darolutamide in Metastatic Castration Resistant Prostate Cancer (mCRPC)
This study will assess the safety and tolerability of valemetostat in combination with darolutamide in participants with Metastatic Castration Resistant Prostate Cancer (mCRPC).
- Being tested
- Valemetostat, Darolutamide
- Keywords
- Metastatic Castration Resistant Prostate Cancer, DS-3201, Valemetostat, Darolutamide, mCRPC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValemetostatDrug
Also called DS-3201
Dose Escalation Part: Valemetostat will be administered at escalating doses. Dose Expansion Part: Valemetostat will be administered at 2 or more dose levels.
DarolutamideDrug
Also called NUBEQA
Dose Escalation Part: Darolutamide will be administered at a standard dose. Dose Expansion Part: Darolutamide will be administered at a standard dose.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 (Dose Escalation) | Experimental | Participants will receive valemetostat at escalating doses in combination with darolutamide. Receives: Drug: Valemetostat; Drug: Darolutamide |
| Part 2 (Dose Expansion) | Experimental | Participants will receive valemetostat at 2 or more dose levels in combination with darolutamide. Receives: Drug: Valemetostat; Drug: Darolutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: From Screening up to approximately 5 years
Secondary outcomes (9)
Prostate-Specific Antigen (PSA) 50 Response Rate
PSA50 response rate is defined as the percentage of participants who achieved a decline in PSA percent change from baseline by at least 50%, with a consecutive confirmation assessment at least 3 weeks later per the PCWG3 modified RECIST v1.1 criteria.
Measured: From Screening up to approximately 5 years
Prostate-Specific Antigen (PSA) 90 Response Rate
PSA90 response rate is defined as the percentage of participants who achieved a decline in PSA percent change from baseline by at least 90%, with a consecutive confirmation assessment at least 3 weeks later per the PCWG3 modified RECIST v1.1 criteria.
Measured: From Screening up to approximately 5 years
Prostate-Specific Antigen (PSA) Nadir Response Rate
PSA nadir response rate is defined as the proportion of participants who achieve a PSA level of ≤ 0.2 ng/mL at any time during the Treatment Period.
Measured: From Screening up to approximately 5 years
Radiographic Progression-Free Survival (rPFS)
rPFS is defined as the time (month) from the start date of trial intervention to the earlier date of the first objective documentation of radiographic disease progression as assessed by the investigator based on the PCWG3 modified RECIST v1.1 criteria or death due to any cause.
Measured: From Screening up to approximately 5 years
Overall Survival (OS)
OS is defined as the time (month) from the start date of trial intervention to the date of death due to any cause.
Measured: From Screening up to approximately 5 years
Time to PSA Progression
Time to PSA progression is defined as the time interval from the start date of trial intervention to PSA progression, per the PCWG3 modified RECIST v1.1 criteria. PSA progression is defined as:
- A ≥25% increase and an absolute increase of ≥2 ng/mL from the nadir, confirmed by a second PSA measurement obtained at least 3 weeks later, in participants who experience a decline in PSA from baseline; OR
- A ≥25% increase and an absolute increase of ≥2 ng/mL from baseline, occurring beyond 12 weeks from treatment initiation, in participants who do not experience a PSA decline from baseline.
Measured: From Screening up to approximately 5 years
Objective Response Rate (ORR)
ORR is defined as the proportion of participants with measurable disease who achieved a BOR of confirmed CR or confirmed PR as assessed by the investigator according to the PCWG3 modified RECIST v1.1 criteria.
Measured: From Screening up to approximately 5 years
Time to First SSRE (symptomatic bone fractures, spinal cord compression, surgery, or radiation to the bone, whichever is first)
Time to first SSRE (symptomatic bone fractures, spinal cord compression, surgery, or radiation to the bone, whichever is first) is defined as the time interval from the start date of trial intervention to the date of the first observed SSRE.
Measured: From Screening up to approximately 5 years
Total and Unbound Plasma Concentration of Valemetostat in Combination with Darolutamide
Measured: Cycle 1: Day 1, Day 8, Day 15. Cycles 2-5: Day 1 (Each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2025
- Study start3 Dec 2025
- Primary completion31 Jan 2028 (estimated)
- Study completion30 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bayer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07244341
- Sponsor's protocol ID
- DS3201-343
- Other IDs
- 2025-522512-16-00, 2025
- Status last verified
- Oct 2026
- First submitted
- 17 Nov 2025
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter Trial Evaluating the Safety, Tolerability, and Efficacy of Valemetostat (DS-3201) in Combination With Darolutamide in Metastatic Castration Resistant Prostate Cancer (mCRPC)
- ClinicalTrials.gov ID
- NCT07244341
- Acronym / sponsor ID
- DS3201-343
- Keywords
- Metastatic Castration Resistant Prostate Cancer, DS-3201, Valemetostat, Darolutamide, mCRPC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Collaborators
- Bayer
- Study start
- 3 Dec 2025 (actual)
- Primary completion
- 31 Jan 2028 (estimated)
- Study completion
- 30 Nov 2029 (estimated)
- First posted
- 24 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the safety and tolerability of valemetostat in combination with darolutamide in participants with Metastatic Castration Resistant Prostate Cancer (mCRPC).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 (Dose Escalation) | Experimental | Drug: Valemetostat, Drug: DarolutamideParticipants will receive valemetostat at escalating doses in combination with darolutamide. |
| Part 2 (Dose Expansion) | Experimental | Drug: Valemetostat, Drug: DarolutamideParticipants will receive valemetostat at 2 or more dose levels in combination with darolutamide. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- The clinical site will screen for the full inclusion criteria per protocol.
- 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).
Key exclusion criteria (9 listed)
- The clinical site will screen for the full exclusion criteria per protocol.
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ValemetostatAlso: DS-3201Dose Escalation Part: Valemetostat will be administered at escalating doses. Dose Expansion Part: Valemetostat will be administered at 2 or more dose levels. | Drug | Part 1 (Dose Escalation), Part 2 (Dose Expansion) |
| DarolutamideAlso: NUBEQADose Escalation Part: Darolutamide will be administered at a standard dose. Dose Expansion Part: Darolutamide will be administered at a standard dose. | Drug | Part 1 (Dose Escalation), Part 2 (Dose Expansion) |
Primary outcome
Part 1: Number of participants with Dose-Limiting Toxicities (DLTs)
Time frame: Day 1 up to Day 28
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.
Part 1 and 2: Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE)
Time frame: From Screening up to approximately 5 years
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).
9 secondary outcomes
Prostate-Specific Antigen (PSA) 50 Response Rate
Time frame: From Screening up to approximately 5 years
Prostate-Specific Antigen (PSA) 90 Response Rate
Time frame: From Screening up to approximately 5 years
Prostate-Specific Antigen (PSA) Nadir Response Rate
Time frame: From Screening up to approximately 5 years
Radiographic Progression-Free Survival (rPFS)
Time frame: From Screening up to approximately 5 years
Overall Survival (OS)
Time frame: From Screening up to approximately 5 years
Time to PSA Progression
Time frame: From Screening up to approximately 5 years
Objective Response Rate (ORR)
Time frame: From Screening up to approximately 5 years
Time to First SSRE (symptomatic bone fractures, spinal cord compression, surgery, or radiation to the bone, whichever is first)
Time frame: From Screening up to approximately 5 years
Total and Unbound Plasma Concentration of Valemetostat in Combination with Darolutamide
Time frame: Cycle 1: Day 1, Day 8, Day 15. Cycles 2-5: Day 1 (Each cycle is 28 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
29 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Valemetostat and Darolutamide in people with Metastatic Castration-resistant Prostate Cancer, run by Daiichi Sankyo at 29 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, China, Australia, Japan, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Contact for Trial Information (908-992-6400, CTRinfo_us@daiichisankyo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Number of participants with Dose-Limiting Toxicities (DLTs) (time frame: Day 1 up to Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.