Study of Pembrolizumab (MK-3475) Plus Docetaxel Versus Placebo Plus Docetaxel in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-921/KEYNOTE-921)-China Extension

NCT04907227 | Terminated Phase 3 Results DMC FDA Drug

• 4 other identifiers: 3475-921 China ExtensionMK-3475-921 China ExtensionKEYNOTE-921194831
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 20

Brief Summary

The purpose of this study is to assess the efficacy and safety of the combination of pembrolizumab (MK-3475) and docetaxel in the treatment of Chinese men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC but have progressed on or are intolerant to Next Generation Hormonal Agent (NHA). There are two primary study hypotheses. Hypothesis 1: The combination of pembrolizumab plus docetaxel plus prednisone is superior to placebo plus docetaxel plus prednisone with respect to Overall Survival (OS). Hypothesis 2: The combination of pembrolizumab plus docetaxel plus prednisone is superior to placebo plus docetaxel plus prednisone with respect to 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.

Conditions

Prostatic Neoplasms

Keywords

Programmed Cell Death 1 (PD 1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL 1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL 2, PD-L2)

Outcome Measures

Primary Outcomes (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 (K-M) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

  Up to 19.8 months

• 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. Radiological progression as per 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 K-M method for censored data. Participants without a rPFS event were censored at the date of last disease assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

  Up to 19.8 months

Secondary Outcomes (10)

• Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST)

  Up to 19.8 months

• Prostate-specific Antigen (PSA) Response Rate

  Up to 19.8 months

• Objective Response Rate (ORR) 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)

  Up to 19.8 months

• Duration of Response (DOR) 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)

  Up to 19.8 months

• Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and Opiate Analgesic Use Assessed by the Analgesic Quantification Algorithm [AQA] Score

  Up to 19.8 months

Study Arms (2)

Pembrolizumab+Docetaxel

EXPERIMENTAL

Participants receive pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.

Biological: Pembrolizumab; Drug: Docetaxel; Drug: Prednisone; Drug: Dexamethasone

Placebo+Docetaxel

PLACEBO COMPARATOR

Participants receive placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.

Drug: Docetaxel; Drug: Prednisone; Drug: Placebo; Drug: Dexamethasone

Interventions

Placebo DRUG

IV infusion

Also known as: Normal saline or dextrose infusion

Placebo+Docetaxel

Dexamethasone DRUG

Oral tablets

Also known as: DECADRON®

Pembrolizumab+Docetaxel; Placebo+Docetaxel

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab+Docetaxel

Docetaxel DRUG

IV infusion

Also known as: TAXOTERE®

Pembrolizumab+Docetaxel; Placebo+Docetaxel

Prednisone DRUG

Oral tablets

Pembrolizumab+Docetaxel; Placebo+Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months prior to screening
• Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
• Has received prior treatment with one (but not more than one) NHA (eg, abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for metastatic hormone-sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC) and either a) progressed through treatment OR b) has become intolerant of the drug
• Has ongoing androgen deprivation with serum testosterone \<50 ng/dL (\<2.0 nM)
• Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
• Participants must agree to the following during the study treatment period and for at least 120 days after the last dose of pembrolizumab or for at least 180 days after the last dose of docetaxel (whichever is longer): Refrain from donating sperm PLUS Use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
• Participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex
• Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed). Participants with bone only or bone predominant disease may provide a bone biopsy sample
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization

You may not qualify if:

• Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications
• Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
• Has an active infection (including tuberculosis) requiring systemic therapy
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
• Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease)
• Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization or who has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to mAbs
• Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g. saw palmetto) prior to randomization
• Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
• Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX-40, CD137)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (20)

Second Affiliated hospital of Anhui Medical University-Urology (Site 1339)

Hefei, Anhui, 230601, China

Location

Peking University First Hospital ( Site 1303)

Beijing, Beijing Municipality, 100034, China

Location

The Fifth Medical Center of PLA General Hospital ( Site 1307)

Beijing, Beijing Municipality, 100071, China

Location

Peking University Third Hospital (Site 1304)

Beijing, Beijing Municipality, 100089, China

Location

Beijing Cancer Hospital ( Site 1305)

Beijing, Beijing Municipality, 100142, China

Location

The First Affiliated Hospital of Xiamen University ( Site 1319)

Xiamen, Fujian, 361000, China

Location

Sun Yat Sen Memorial Hospital ( Site 1323)

Guangzhou, Guangdong, 510220, China

Location

The First Affiliated Hospital of Guangzhou Medical University ( Site 1330)

Guangzhou, Guangdong, 510230, China

Location

Sun Yat-Sen University Cancer Center (Site 1334)

Guangzhou, Guangdong, 510663, China

Location

Harbin Medical University Cancer Hospital (Site 1326)

Harbin, Heilongjiang, 150081, China

Location

Henan Cancer Hospital ( Site 1321)

Zhengzhou, Henan, 450008, China

Location

Hubei Cancer Hospital ( Site 1329)

Wuhan, Hubei, 430079, China

Location

Hunan Cancer Hospital ( Site 1320)

Changsha, Hunan, 410013, China

Location

Nanjing Drum Tower Hospital ( Site 1312)

Nanjing, Jiangsu, 210008, China

Location

Zhongshan Hospital Fudan University ( Site 1301)

Shanghai, Shanghai Municipality, 200032, China

Location

Renji Hospital Shanghai Jiao Tong University School of Medicine (Site 1335)

Shanghai, Shanghai Municipality, 200127, China

Location

Fudan University Shanghai Cancer Center ( Site 1300)

Shanghai, Shanghai Municipality, 201321, China

Location

The First Affiliated Hospital of Xi an Jiaotong University (Site 1315)

Xian, Shanxi, 710061, China

Location

The Second Affiliated Hospital of Zhejiang University School of Medicine ( Site 1309)

Hangzhou, Zhejiang, 310009, China

Location

Zhejiang Provincial People's Hospital ( Site 1310)

Hangzhou, Zhejiang, 310014, China

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Prostatic Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Docetaxel; Prednisone; Saline Solution; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Pregnadienetriols; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2021
• First Posted: May 28, 2021
• Study Start: September 23, 2020
• Primary Completion: August 3, 2022
• Study Completion: July 18, 2023
• Last Updated: July 12, 2024
• Results First Posted: August 4, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

CN (20)