Castration-Resistant Prostatic Cancer, Metastasis
Conditions
Brief summary
The purpose of this substudy is to assess the efficacy and safety of ifinatamab deruxtecan (I-DXd), given alone or with other treatments in participants with metastatic castration-resistant prostate cancer (mCRPC). The goals of this study are to learn about: * The safety of the study treatment and if people tolerate it. * A safe dose level of I-DXd that can be used with other treatments. * Participant levels of prostate specific antigen (PSA) during treatment.
Detailed description
This sub study MK-2400-01A assesses treatments for metastatic castration-resistant prostate cancer (mCRPC). The master screening protocol is MK-2400-U01
Interventions
DRUGDocetaxel
Administered via Intravenous (IV) infusion at a specified dose on specified days
Administered via IV infusion at a specified dose on specified days
DRUGMK-5684
Administered orally at a specified dose on specified days
DRUGAbiraterone
Administered orally at a specified dose on specified days
DRUGEnzalutamide
Administered orally at a specified dose on specified days
DRUGRescue Medication
Before each dose of I-DXd, participants are required to take premedication for prevention of nausea and vomiting with a 2- or 3-drug combination regimen (eg, dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) per approved product label.
Sponsors
Merck Sharp & Dohme LLC
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology * Has prostate cancer progression while on androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before Screening * Has current evidence of metastatic disease * Has received prior treatment with 1 or 2 androgen receptor pathway inhibitors (ARPIs) and progressed during or after treatment * Participants receiving bone resorptive therapy (including, but not limited to bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks before allocation/randomization * An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 10 days before allocation/randomization * Has prior treatment with poly-ADP-ribose polymerase inhibitors (PARPi) if indicated by local approved regimen or were deemed ineligible to receive PARPi by the investigator
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) - Combination Arms Only | Up to approximately 21 days | The following events if considered drug related by the Investigator, will be considered a DLT: Grade 4 nonhematologic toxicity (not based on laboratory value); Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia associated with clinically significant bleeding; Nonhematologic AEs ≥Grade 3 with exceptions; Grade 3 or Grade 4 non-hematologic laboratory values if requires medical intervention, leads to hospitalization, persists for \>1 week, or results in a Drug-induced Liver Injury with exceptions; Grade 3 or 4 febrile neutropenia; Study intervention - related toxicities that lead to discontinuation of study treatment during Cycle 1; Prolonged delay (\>2 weeks) in initiating Cycles 2 due to treatment-related toxicity; Missing \>25% of study intervention doses as a result of treatment-related AE during Cycle 1; Grade 5 toxicity. |
| Efficacy Phase: Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 54 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Efficacy Phase: Number of Participants Who Discontinued Study Intervention Due to an AE | Up to approximately 24 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Efficacy Phase: Prostate-Specific Antigen (PSA) response rate | Up to approximately 54 months | PSA response is defined per prostate cancer working group (PCWG) criteria as a reduction in the PSA level of 50% or more from baseline measured at consecutive assessments at least 3 weeks apart. |
| Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) - Combination Arms Only | Up to approximately 21 days | The following events if considered drug related by the Investigator, will be considered a DLT: Grade 4 nonhematologic toxicity (not based on laboratory value); Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia associated with clinically significant bleeding; Nonhematologic AEs ≥Grade 3 with exceptions; Grade 3 or Grade 4 non-hematologic laboratory values if requires medical intervention, leads to hospitalization, persists for \>1 week, or results in a Drug-induced Liver Injury with exceptions; Grade 3 or 4 febrile neutropenia; Study intervention - related toxicities that lead to discontinuation of study treatment during Cycle 1; Prolonged delay (\>2 weeks) in initiating Cycles 2 due to treatment-related toxicity; Missing \>25% of study intervention doses as a result of treatment-related AE during Cycle 1; Grade 5 toxicity. |
| Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE) - Combination Arms Only | Up to approximately 21 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE - Combination Arms Only | Up to approximately 21 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 54 months | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per PCWG-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. |
| Radiographic Progression-Free Survival (rPFS) | Up to approximately 54 months | rPFS is defined as the time from randomization to the first documented progressive disease (PD) per PCWG-modified RECIST 1.1 based on BICR or death due to any cause, whichever occurred first. Per PCWG-modified RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions or ≥2 new bone lesions was also considered PD. PCWG-modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (\>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1 and PCWG rules include new bone lesions. The rPFS per PCWG-modified RECIST as assessed by BICR for all participants is presented. The nonparametric Kaplan-Meier method will be used to estimate the rPFS curve in each treatment arm |
| Overall Survival (OS) | Up to approximately 54 months | Overall survival (OS) is defined as the time from randomization to death due to any cause. The nonparametric Kaplan-Meier method will be used to estimate the survival curves. |
| Duration of Response (DOR) | Up to approximately 54 months | DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per PCWG-modified RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of ≥ 2 new bone lesions is also considered PD. DOR as assessed by BICR is presented. The nonparametric Kaplan-Meier method will be used to estimate the DOR in each treatment arm. |
| Time from allocation/randomization to initiation of the first subsequent anticancer therapy (TFST) | Up to approximately 54 months | TFST is defined as the time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first. The nonparametric Kaplan-Meier method will be used to estimate the TFST in each treatment arm. |
| Time to Prostate-Specific Antigen (PSA) Progression | Up to approximately 54 months | Time to PSA progression is defined as the time from randomization to PSA progression. Participants without PSA progression will be censored at the last PSA assessment date. The PSA progression date is defined as the date of: 1\) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, OR 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline. |
| Time to pain progression (TTPP) | Up to approximately 54 months | The time from allocation/randomization to pain progression based on the Brief Pain Inventory-Short Form (BPI-SF) Item 3 "worst pain in 24 hours" and by the Analgesic Quantification Algorithm (AQA) score. |
Countries
Argentina, Australia, Brazil, Canada, Chile, France, Germany, Ireland, Israel, Italy, Netherlands, New Zealand, Poland, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed