Prostatic NeoplasmsPhase 3NCT04907227
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
A Phase 3 study testing Pembrolizumab, Docetaxel and Prednisone in people with Prostatic Neoplasms, run by Merck Sharp & Dohme LLC at 20 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- Pembrolizumab, Docetaxel and Prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 20 sitesChina
- Study dates
- 23 Sep 2020to 18 Jul 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
China20 sites
Peking University First Hospital ( Site 1303)
Beijing, Beijing Municipality, 100034
The Fifth Medical Center of PLA General Hospital ( Site 1307)
Beijing, Beijing Municipality, 100071
Peking University Third Hospital (Site 1304)
Beijing, Beijing Municipality, 100089
Beijing Cancer Hospital ( Site 1305)
Beijing, Beijing Municipality, 100142
Hunan Cancer Hospital ( Site 1320)
Changsha, Hunan, 410013
Sun Yat Sen Memorial Hospital ( Site 1323)
Guangzhou, Guangdong, 510220
The First Affiliated Hospital of Guangzhou Medical University ( Site 1330)
Guangzhou, Guangdong, 510230
Sun Yat-Sen University Cancer Center (Site 1334)
Guangzhou, Guangdong, 510663
The Second Affiliated Hospital of Zhejiang University School of Medicine ( Site 1309)
Hangzhou, Zhejiang, 310009
Zhejiang Provincial People's Hospital ( Site 1310)
Hangzhou, Zhejiang, 310014
Harbin Medical University Cancer Hospital (Site 1326)
Harbin, Heilongjiang, 150081
Second Affiliated hospital of Anhui Medical University-Urology (Site 1339)
Hefei, Anhui, 230601
Nanjing Drum Tower Hospital ( Site 1312)
Nanjing, Jiangsu, 210008
Zhongshan Hospital Fudan University ( Site 1301)
Shanghai, Shanghai Municipality, 200032
Renji Hospital Shanghai Jiao Tong University School of Medicine (Site 1335)
Shanghai, Shanghai Municipality, 200127
Fudan University Shanghai Cancer Center ( Site 1300)
Shanghai, Shanghai Municipality, 201321
Hubei Cancer Hospital ( Site 1329)
Wuhan, Hubei, 430079
The First Affiliated Hospital of Xiamen University ( Site 1319)
Xiamen, Fujian, 361000
The First Affiliated Hospital of Xi an Jiaotong University (Site 1315)
Xian, Shanxi, 710061
Henan Cancer Hospital ( Site 1321)
Zhengzhou, Henan, 450008
About this study
Official title: A Phase 3, Randomized, Double-blind Study of Pembrolizumab (MK-3475) Plus Docetaxel Plus Prednisone Versus Placebo Plus Docetaxel Plus Prednisone in Participants With Chemotherapy-naïve Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Have Progressed on a Next Generation Hormonal Agent (NHA) (KEYNOTE-921)
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.
Read more
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.
Read the 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
- Being tested
- Pembrolizumab, Docetaxel, Prednisone, Placebo, Dexamethasone
- 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)
- Medical subject headings
- Prostatic Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called MK-3475, KEYTRUDA®
IV infusion
DocetaxelDrug
Also called TAXOTERE®
IV infusion
PrednisoneDrug
Oral tablets
PlaceboDrug
Also called Normal saline or dextrose infusion
IV infusion
DexamethasoneDrug
Also called DECADRON®
Oral tablets
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Docetaxel; Drug: Prednisone; Drug: Placebo; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 19.8 months
Secondary outcomes (10)
Time to Initiation of the First Subsequent Anti-cancer Therapy (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 K-M method for censored data. Any participant not known to have further subsequent therapy or death was censored at the last known time that no subsequent new anti-cancer therapy was received. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.
Measured: Up to 19.8 months
Prostate-specific Antigen (PSA) Response Rate
The Prostate-specific Antigen (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. The analysis was performed on participants who had baseline PSA measurements. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.
Measured: 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)
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 bone 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). Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.
Measured: 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)
DOR was the time from first evidence of complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease [NED] on bone scan per PCWG) or partial response (PR: ≥30% decrease in the sum of diameters of target lesions per RECIST 1.1; non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG) until progressive disease (PD) or death. PD per RECIST 1.1 was ≥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 ≥5 mm. PD per PCWG was the appearance of ≥2 new bone lesions on bone scan that were confirmed to not represent tumor flare and persisted for ≥6 weeks. DOR was calculated using the product-limit K-M method. Participants who did not progress were censored at last disease assessment. Per protocol final analysis for this outcome measure was done with the primary completion data cutoff.
Measured: 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
TTPP was time from randomization to pain progression (PP) per BPI-SF Item 3 and AQA score. BPI-SF assesses pain intensity; for item 3, responses to "Please rate your pain at its worst in the last 24 hours" are scored from 0 (no pain) to 10 (worst pain). A higher score indicates greater pain. AQA captures the intensity of analgesic use, scored from 0 (no use) to 7 (strong opioid use). A higher score indicates higher intensity of use.
For participants asymptomatic at baseline, PP was ≥2-point change from baseline in Item 3 score OR opioid use initiation. For those symptomatic at baseline, PP was ≥2-point change from baseline in Item 3 score, a score of ≥4, no decrease in average opioid use OR any increase in opioid use (e.g. 1 point change in AQA score). TTPP was assessed by product-limit K-M method. Participants with >2 consecutive unevaluable visits were censored at last assessment. Per protocol final analysis for this outcome measure was done with the primary completion data cutoff.
Measured: Up to 19.8 months
Time to First Symptomatic Skeletal-related Event (SSRE)
SSRE was the time from randomization to the first symptomatic skeletal-related event defined as: 1. use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms 2. occurrence of new symptomatic pathologic bone fracture (vertebral or non-vertebral) 3. occurrence of spinal cord compression 4. tumor-related orthopedic surgical intervention, whichever occurs first. The SSRE was calculated using the product-limit K-M method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.
Measured: Up to 19.8 months
Time to Prostate-specific Antigen (PSA) Progression
The 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 was PSA decline from baseline; OR 2. ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there was no PSA decline from baseline. Time to PSA progression was calculated using the product-limit K-M method for censored data. Participants without PSA progression were censored at the last evaluable assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.
Measured: Up to 19.8 months
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 (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 K-M method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.
Measured: Up to 19.8 months
Number of Participants Who Experienced an Adverse Event (AE)
An AE was 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 could therefore have been 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. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff. The number of participants who experienced an AE is presented.
Measured: Up to 17 months
Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE)
An AE was 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 could therefore have been 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. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff. The number of participants who discontinued study treatment due to an AE is presented.
Measured: Up to 14 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2021
- Study start23 Sep 2020
- Primary completion3 Aug 2022
- Study completion18 Jul 2023
Why it stopped: The data did not support study endpoints
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04907227
- Sponsor's protocol ID
- 3475-921 China Extension
- Other IDs
- MK-3475-921 China Extension, KEYNOTE-921, 194831
- Status last verified
- Jun 2024
- First submitted
- 26 May 2021
- Last updated
- 12 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-blind Study of Pembrolizumab (MK-3475) Plus Docetaxel Plus Prednisone Versus Placebo Plus Docetaxel Plus Prednisone in Participants With Chemotherapy-naïve Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Have Progressed on a Next Generation Hormonal Agent (NHA) (KEYNOTE-921)
- ClinicalTrials.gov ID
- NCT04907227
- Acronym / sponsor ID
- 3475-921 China Extension
- 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)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The data did not support study endpoints
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 23 Sep 2020 (actual)
- Primary completion
- 3 Aug 2022 (actual)
- Study completion
- 18 Jul 2023 (actual)
- First posted
- 28 May 2021 (actual)
- Results
- Posted 4 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab+Docetaxel | Experimental | Biological: Pembrolizumab, Drug: Docetaxel, Drug: Prednisone, Drug: DexamethasoneParticipants 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. |
| Placebo+Docetaxel | Placebo comparator | Drug: Docetaxel, Drug: Prednisone, Drug: Placebo, Drug: DexamethasoneParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: MK-3475, KEYTRUDA®IV infusion | Biological | Pembrolizumab+Docetaxel |
| DocetaxelAlso: TAXOTERE®IV infusion | Drug | Pembrolizumab+Docetaxel, Placebo+Docetaxel |
| PrednisoneOral tablets | Drug | Pembrolizumab+Docetaxel, Placebo+Docetaxel |
| PlaceboAlso: Normal saline or dextrose infusionIV infusion | Drug | Placebo+Docetaxel |
| DexamethasoneAlso: DECADRON®Oral tablets | Drug | Pembrolizumab+Docetaxel, Placebo+Docetaxel |
Primary outcome
Overall Survival (OS)
Time frame: Up to 19.8 months
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.
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)
Time frame: Up to 19.8 months
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.
10 secondary outcomes
Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST)
Time frame: Up to 19.8 months
Prostate-specific Antigen (PSA) Response Rate
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: Up to 19.8 months
Time to First Symptomatic Skeletal-related Event (SSRE)
Time frame: Up to 19.8 months
Time to Prostate-specific Antigen (PSA) Progression
Time frame: Up to 19.8 months
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 (BICR)
Time frame: Up to 19.8 months
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to 17 months
Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE)
Time frame: Up to 14 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pembrolizumab, Docetaxel and Prednisone in people with Prostatic Neoplasms, run by Merck Sharp & Dohme LLC at 20 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: Up to 19.8 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2024.