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
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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. A total of approximately 150 Chinese participants will be enrolled.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pembrolizumab+Docetaxel On Day 1 of each 21-day cycle, participants receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours and 1 hour prior to docetaxel administration PLUS docetaxel 75 mg/m^2 by intravenous (IV) infusion for up to a maximum of 10 cycles (approximately 7 months). Participants receive prednisone 5 mg by oral tablets twice daily during each docetaxel cycle up to a maximum of 10 cycles (approximately 7 months). Participants also receive pembrolizumab 200 mg by IV infusion on day 1 of each 21-day cycle for up to a maximum of 35 cycles (approximately 2 years). |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Docetaxel
IV infusion
Other Names:
Drug: Prednisone
Oral tablets
Drug: Dexamethasone
Oral tablets
Other Names:
|
| Placebo Comparator: Placebo+Docetaxel On Day 1 of each 21-day cycle, participants receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours and 1 hour prior to docetaxel administration PLUS docetaxel 75 mg/m^2 by IV infusion for up to a maximum of 10 cycles (approximately 7 months). Participants receive prednisone 5 mg by oral tablets twice daily during each docetaxel cycle up to a maximum of 10 cycles (approximately 7 months). Participants also receive placebo by IV infusion on day 1 of each 21-day cycle for up to a maximum of 35 cycles (approximately 2 years). |
Drug: Docetaxel
IV infusion
Other Names:
Drug: Prednisone
Oral tablets
Drug: Placebo
IV infusion
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [Up to approximately 28 months]
Time from randomization to death due to any cause
- 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 [Up to approximately 28 months]
Time from randomization to radiographic progression, or death due to any cause, whichever occurs first
Secondary Outcome Measures
- Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST) [Up to approximately 28 months]
Time from randomization to initiation of the first subsequent anti-cancer therapy or death, whichever occurs first
- Prostate-specific Antigen (PSA) Response Rate [Up to approximately 28 months]
Percentage of participants in the analysis population who have a negative change (decrease) in PSA level of ≥50% measured twice ≥3 weeks apart
- 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 [Up to approximately 28 months]
Percentage of participants in the analysis population who have a best overall response of either confirmed Complete Response (CR) or a confirmed Partial Response (PR) per PCWG-modified RECIST 1.1
- 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 [Up to approximately 28 months]
Time from first documented evidence of confirmed Complete Response (CR) or Partial Response (PR) per PCWG-modified RECIST 1.1 until disease progression or death from any cause, whichever occurs first
- 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 (Analgesic Quantification Algorithm [AQA] Score) [Up to approximately 28 months]
Time from randomization to pain progression. In this study, pain progression will be assessed by participant responses to Item 3 of the BPI-SF and participant AQA Scores which are both assessed by participants daily for 7 consecutive days
- Time to First Symptomatic Skeletal-related Event (SSRE) [Up to approximately 28 months]
Time from randomization to the first SSRE. SSRE is defined as radiation to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathological fracture, spinal cord compression, or surgery to bone
- Time to Prostate-specific Antigen (PSA) Progression [Up to approximately 28 months]
Time from randomization to PSA progression. 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 Radiographic Soft Tissue Progression Per Soft Tissue Rules of 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 [Up to approximately 28 months]
Time from randomization to radiographic soft tissue progression per PCWG-modified RECIST 1.1
- Number of Participants Who Experience an Adverse Event (AE) [Up to approximately 28 months]
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment
- Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [Up to approximately 28 months]
The number of participants who discontinue study treatment due to an AE will be presented
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Second Affiliated hospital of Anhui Medical University-Urology (Site 1339) | Hefei | Anhui | China | 230601 |
| 2 | Peking University First Hospital ( Site 1303) | Beijing | Beijing | China | 100034 |
| 3 | The Fifth Medical Center of PLA General Hospital ( Site 1307) | Beijing | Beijing | China | 100071 |
| 4 | Peking University Third Hospital (Site 1304) | Beijing | Beijing | China | 100089 |
| 5 | Beijing Cancer Hospital ( Site 1305) | Beijing | Beijing | China | 100142 |
| 6 | The First Affiliated Hospital of Xiamen University ( Site 1319) | Xiamen | Fujian | China | 361000 |
| 7 | Sun Yat Sen Memorial Hospital ( Site 1323) | Guangzhou | Guangdong | China | 510220 |
| 8 | The First Affiliated Hospital of Guangzhou Medical University ( Site 1330) | Guangzhou | Guangdong | China | 510230 |
| 9 | Sun Yat-Sen University Cancer Center (Site 1334) | Guangzhou | Guangdong | China | 510663 |
| 10 | Harbin Medical University Cancer Hospital (Site 1326) | Harbin | Heilongjiang | China | 150081 |
| 11 | Henan Cancer Hospital ( Site 1321) | Zhengzhou | Henan | China | 450008 |
| 12 | Hubei Cancer Hospital ( Site 1329) | Wuhan | Hubei | China | 430079 |
| 13 | Hunan Cancer Hospital ( Site 1320) | Changsha | Hunan | China | 410013 |
| 14 | Nanjing Drum Tower Hospital ( Site 1312) | Nanjing | Jiangsu | China | 210008 |
| 15 | Zhongshan Hospital Fudan University ( Site 1301) | Shanghai | Shanghai | China | 200032 |
| 16 | Renji Hospital Shanghai Jiao Tong University School of Medicine (Site 1335) | Shanghai | Shanghai | China | 200127 |
| 17 | Fudan University Shanghai Cancer Center ( Site 1300) | Shanghai | Shanghai | China | 201321 |
| 18 | The First Affiliated Hospital of Xi an Jiaotong University (Site 1315) | Xian | Shanxi | China | 710061 |
| 19 | The Second Affiliated Hospital of Zhejiang University School of Medicine ( Site 1309) | Hangzhou | Zhejiang | China | 310009 |
| 20 | Zhejiang Provincial People's Hospital ( Site 1310) | Hangzhou | Zhejiang | China | 310014 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 3475-921 China Extension
- MK-3475-921 China Extension
- KEYNOTE-921
- 194831