Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)-China Extension

Browse trials for

• Parkinson Disease 4, Autosomal Dominant Lewy Body 152

Keywords

• Programmed Cell Death-1 (PD1, PD-1),
• Programmed Death-Ligand 1 (PDL1, PD-L1)

Parkinson Disease 4, Autosomal Dominant Lewy Body

152 studies on the registry are indexed under Parkinson Disease 4, Autosomal Dominant Lewy Body; 34 are open to participants now.

This study's enrollment of 186 is below the median of 302 across 141 interventional studies indexed under Parkinson Disease 4, Autosomal Dominant Lewy Body.

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Study arms

• Experimental
  Pembrolizumab + Enzalutamide + ADT

  Starting on Day 1 of each 21-day cycle, participants receive 200 mg pembrolizumab intravenously (IV) every 3 weeks (q3w) for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.

  Biological: Pembrolizumab · Drug: Enzalutamide · Drug: Androgen Deprivation Therapy (ADT)

• Placebo comparator
  Placebo + Enzalutamide + ADT

  Starting on Day 1 of each 21-day cycle, participants receive placebo IV q3w for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.

  Drug: Enzalutamide · Drug: Androgen Deprivation Therapy (ADT) · Other: Placebo

Interventions

• BiologicalPembrolizumab

  Pembrolizumab is administered as an IV infusion at 200 mg on Day 1 of each 21-day cycle for up to 35 cycles.

  Also known as: KEYTRUDA®, MK-3475

• DrugEnzalutamide

  Enzalutamide is administered orally as capsules/tablets at a dosage of 160 mg daily. Enzalutamide is administered continuously until criteria for discontinuation are met.

  Also known as: XTANDI®

• DrugAndrogen Deprivation Therapy (ADT)

  Stable regimen of ADT (LHRH agonist or antagonist) at a dose and frequency of administration that is consistent with the local product label.

• OtherPlacebo

  Placebo infusion solution is administered as an IV infusion on Day 1 of each 21-day cycle for up to 35 cycles.

Primary outcomes

1. Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

   rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.

   Time frame: Up to approximately 17 months

2. Overall Survival (OS)

   OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.

   Time frame: Up to approximately 17 months

Secondary outcomes

1. Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)

   TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product limit (Kaplan-Meier) method for censored data. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy.

   Time frame: Up to Approximately 17 months

2. Time to First Symptomatic Skeletal-related Event (TTSSRE)

   TTSSRE was the time from randomization to the first symptomatic skeletal-related event defined as: use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral), occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention, whichever occurs first. The TTSSRE was calculated using the Kaplan-Meier method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment.

   Time frame: Up to Approximately 17 months

3. Time to Prostate-specific Antigen (PSA) Progression

   Time to PSA progression was the time from randomization to PSA progression. The PSA progression date was 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 PSA was calculated using Kaplan-Meier method for censored data. Participants without PSA progression were censored at the last PSA date.

   Time frame: Up to Approximately 17 months

4. Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR

   The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was 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 was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment.

   Time frame: Up to Approximately 17 months

5. Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item #3 ("Worst Pain in 24 Hours") and Opiate Use

   TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF. Pain progression was defined as: 1) For participants asymptomatic at baseline: a \>2-point change from baseline in the average BPI-SF item 3 score at 2 consecutive visits or initiation of opioid use for pain 2) For participants symptomatic at baseline (average BPI-SF Item 3 score \>0 and/or currently taking opioids; a \>2-point change from baseline in the average BPI-SF Item 3 score and the average worst pain score \>4 and no decrease in average opioid use. TTPP was calculated using the Kaplan-Meier method for censored data. Participants who had \> 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.

   Time frame: Up to Approximately 17 months

6. Time From Randomization to Disease Progression as Determined by Investigator Assessment After Next-line of Therapy or Death From Any Cause, Whichever Occurs First (PFS2)

   PFS2 was defined as the time from randomization to disease progression as determined by investigator assessment of radiological or clinical progression after next-line of therapy or death from any cause, whichever occurs first.

   Time frame: Up to Approximately 17 months

7. Prostate-specific Antigen (PSA) Response Rate

   PSA response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by \>50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed \>3 weeks from the original response.

   Time frame: Up to Approximately 17 Months

8. Prostate-specific Antigen (PSA) Undetectable

   PSA undetectable rate was defined as the percentage of participants with detectable PSA (\> 0.2 ng/mL) at baseline, which becomes undetectable (\< 0.2 ng/mL) during study treatment.

   Time frame: Up to Approximately 17 Months

9. Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR

   ORR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on base scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable \[NE\], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG).

   Time frame: Up to Approximately 17 Months

10. Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR

    DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 was 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 a least 5 mm. PD per PCWG was the appearance of \>2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for \>6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data.

    Time frame: Up to Approximately 17 Months

11. Number of Participants Who Experience an Adverse Event (AE)

    An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. Number of participants who experienced one or more AEs were reported.

    Time frame: Up to approximately 50 months

12. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

    An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. Number of participants who discontinued study intervention (includes any study medication given during the study) due to an AE were reported.

    Time frame: Up to approximately 49 months

Baseline characteristics

Related links

• Merck Clinical Trials Information ↗

Study documents

• Protocol and statistical analysis plan · May 15, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf