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

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexMale
Age18+
SponsorDaiichi Sankyo

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

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,

Trial design

Design model

Single group

Treatments tested in this trial

  • 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.

  • Darolutamide

    Drug

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

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Part 1 (Dose Escalation)Experimental treatment 2 interventions
Group B: Part 2 (Dose Expansion)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Day 1 up to Day 28
2

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).

Time frame
From Screening up to approximately 5 years

Secondary outcomes

1

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.

Time frame
From Screening up to approximately 5 years
2

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.

Time frame
From Screening up to approximately 5 years
3

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.

Time frame
From Screening up to approximately 5 years
4

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.

Time frame
From Screening up to approximately 5 years

Other outcomes

Sponsors and contacts

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