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

NCT ID: NCT04907227

Last Updated: 2024-07-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-23
• Study Completion Date: 2023-07-18

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.

Detailed Description

The China extension study will include participants previously enrolled in China in the global study for MK-3475-921 (NCT03834506) plus those enrolled during the China extension enrollment period.

With Amendment 6 (effective date: 29-Sep-2022), all participants were unblinded and placebo treatment was stopped. Participants deemed to derive clinical benefit from treatment may have continued at the discretion of the investigator.

Conditions

Prostatic Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Pembrolizumab+Docetaxel

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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion

Docetaxel

Intervention Type: DRUG

IV infusion

Prednisone

Intervention Type: DRUG

Oral tablets

Dexamethasone

Intervention Type: DRUG

Oral tablets

Placebo+Docetaxel

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.

Group Type: PLACEBO_COMPARATOR

Docetaxel

Intervention Type: DRUG

IV infusion

Prednisone

Intervention Type: DRUG

Oral tablets

Placebo

Intervention Type: DRUG

IV infusion

Dexamethasone

Intervention Type: DRUG

Oral tablets

Interventions

Pembrolizumab

IV infusion

Intervention Type: BIOLOGICAL

Docetaxel

IV infusion

Intervention Type: DRUG

Prednisone

Oral tablets

Intervention Type: DRUG

Placebo

IV infusion

Intervention Type: DRUG

Dexamethasone

Oral tablets

Intervention Type: DRUG

Other Intervention Names

MK-3475; KEYTRUDA®; TAXOTERE®; Normal saline or dextrose infusion; DECADRON®

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)
• Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC
• Has hypersensitivity to docetaxel or polysorbate 80
• Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
• Has received prior targeted small molecule therapy or abiraterone acetate, enzalutamide, apalutamide, or darolutamide within 4 weeks prior to the first dose of study treatment, or has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to a previously administered agent
• Has received prior radiotherapy to within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
• Has received a live vaccine within 30 days prior to randomization
• Has received treatment with 5α reductase inhibitors (eg, finasteride or dutasteride), estrogens, and/or cyproterone within 4 weeks prior to randomization
• Has received prior treatment with ketoconazole for prostate cancer
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
• Has a "superscan" bone scan
• Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
• Has had an allogenic tissue/solid organ transplant

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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

Hefei, Anhui, China

Peking University First Hospital ( Site 1303)

Beijing, Beijing Municipality, China

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

Beijing, Beijing Municipality, China

Peking University Third Hospital (Site 1304)

Beijing, Beijing Municipality, China

Beijing Cancer Hospital ( Site 1305)

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Xiamen University ( Site 1319)

Xiamen, Fujian, China

Sun Yat Sen Memorial Hospital ( Site 1323)

Guangzhou, Guangdong, China

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

Guangzhou, Guangdong, China

Sun Yat-Sen University Cancer Center (Site 1334)

Guangzhou, Guangdong, China

Harbin Medical University Cancer Hospital (Site 1326)

Harbin, Heilongjiang, China

Henan Cancer Hospital ( Site 1321)

Zhengzhou, Henan, China

Hubei Cancer Hospital ( Site 1329)

Wuhan, Hubei, China

Hunan Cancer Hospital ( Site 1320)

Changsha, Hunan, China

Nanjing Drum Tower Hospital ( Site 1312)

Nanjing, Jiangsu, China

Zhongshan Hospital Fudan University ( Site 1301)

Shanghai, Shanghai Municipality, China

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

Shanghai, Shanghai Municipality, China

Fudan University Shanghai Cancer Center ( Site 1300)

Shanghai, Shanghai Municipality, China

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

Xian, Shanxi, China

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

Hangzhou, Zhejiang, China

Zhejiang Provincial People's Hospital ( Site 1310)

Hangzhou, Zhejiang, China

Countries

China

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

MK-3475-921 China Extension

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-921

Identifier Type: OTHER

Identifier Source: secondary_id

194831

Identifier Type: REGISTRY

Identifier Source: secondary_id

3475-921 China Extension

Identifier Type: -

Identifier Source: org_study_id