Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
Metastatic Castration Resistant Prostate Cancer, DS-3201, Valemetostat, Darolutamide, mCRPC
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).
Interventions
DRUGValemetostat
Dose Escalation Part: Valemetostat will be administered at escalating doses. Dose Expansion Part: Valemetostat will be administered at 2 or more dose levels.
DRUGDarolutamide
Dose Escalation Part: Darolutamide will be administered at a standard dose. Dose Expansion Part: Darolutamide will be administered at a standard dose.
Sponsors
Daiichi Sankyo
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of participants with Dose-Limiting Toxicities (DLTs) | 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) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prostate-Specific Antigen (PSA) 50 Response Rate | From Screening up to approximately 5 years | 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. |
| Prostate-Specific Antigen (PSA) 90 Response Rate | From Screening up to approximately 5 years | 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. |
| Prostate-Specific Antigen (PSA) Nadir Response Rate | From Screening up to approximately 5 years | 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. |
| Radiographic Progression-Free Survival (rPFS) | From Screening up to approximately 5 years | 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. |
| Overall Survival (OS) | From Screening up to approximately 5 years | OS is defined as the time (month) from the start date of trial intervention to the date of death due to any cause. |
| Time to PSA Progression | From Screening up to approximately 5 years | 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. |
| Objective Response Rate (ORR) | From Screening up to approximately 5 years | 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. |
| Time to First SSRE (symptomatic bone fractures, spinal cord compression, surgery, or radiation to the bone, whichever is first) | 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) is defined as the time interval from the start date of trial intervention to the date of the first observed SSRE. |
| Total and Unbound Plasma Concentration of Valemetostat in Combination with Darolutamide | Cycle 1: Day 1, Day 8, Day 15. Cycles 2-5: Day 1 (Each cycle is 28 days) | — |
Countries
China, Ireland, Japan, United States
Contacts
CONTACTContact for Trial Information
Outcome results
None listed