Phase 3 Study of Pembrolizumab/Placebo plus Enzalutamide plus ADT in mHSPC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 May 2020 → 8 Apr 2026

Decision date (initial)

2024-01-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-507024-24-00

EudraCT number

2019-003633-41

WHO UTN

U1111-1294-9592

ClinicalTrials.gov

NCT04191096

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacogenomic, Therapy, Safety, Pharmacoeconomic, Diagnosis, Efficacy

1. To compare pembrolizumab (MK-3475) plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT with respect to rPFS per PCWG-modified RECIST 1.1 as assessed by BICR where soft tissue will be assessed per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and bone disease will be assessed per PCWG criteria.
2. To compare pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT with respect to OS.

Secondary objectives 5

1. To compare pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT with respect to TFST.
2. To compare pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT with respect to TTSSRE.
3. To assess pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT with respect to the: time to PSA progression; time to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1, as assessed by BICR; TTPP; and PFS2.
4. To assess pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT with respect to the: PSA response rate; PSA undetectable rate; and ORR and DOR per PCWG-modified RECIST 1.1 as assessed by BICR.
5. To assess the safety and tolerability of pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT.

Conditions and MedDRA coding

Metastatic hormone sensitive prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male Participants with histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
2. Has metastatic disease assessed by investigator and verified by BICR by either ≥2 bone lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance imaging (CT/MRI)
3. Willing to maintain continuous ADT with a LHRH agonists or antagonists during study treatment or have a history of bilateral orchiectomy
4. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 10 days of randomization
5. Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
6. Has adequate organ function
7. 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
8. Male participants must agree to the following during the intervention period and for at least 120 days after the last dose of study intervention: Refrain from donating sperm PLUS either be abstinent from heterosexual intercourse and agree to remain abstinent OR agree to use contraception, unless confirmed to be azoospermic
9. Male participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex

Exclusion criteria 23

1. Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
2. Has an active autoimmune disease that has required systemic treatment in past 2 years
3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
4. 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
5. Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
6. Has an active infection (including tuberculosis) requiring systemic therapy
7. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
8. Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
9. Has known or suspected central nervous system (CNS) metastases and/or carcinomatous meningitis
10. Has a history of seizure or any condition that may predispose to seizure
11. Has a history of loss of consciousness within 12 months of screening
12. Has had myocardial infarction or uncontrolled angina within 6 months prior to randomization, or has New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure
13. Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit
14. Has a history of clinically significant ventricular arrhythmias
15. Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
16. Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate cancer for >39 months in duration or within 9 months prior to randomization or with evidence of disease progression while receiving ADT
17. Has had prior treatment with a next generation hormonal agent (eg, abiraterone, enzalutamide, apalutamide, darolutamide)
18. 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 coinhibitory T-cell receptor
19. Has received a live vaccine within 30 days prior to randomization
20. Has a "superscan" bone scan
21. Has had an allogenic tissue/solid organ transplant
22. 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
23. Has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer with the following exceptions: a) Up to 3 months of ADT or orchiectomy with or without concurrent first-generation antiandrogens, if patient was not treated with docetaxel b) May have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to randomization c) For participants with low volume metastatic disease, may have 1 course of definitive radiotherapy if it was administered at least 4 weeks prior to randomization d) Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of randomization and no evidence of disease progression. In these participants up to 6 months of ADT permitted

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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
2. Overall Survival (OS)

Secondary endpoints 12

1. Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)
2. Time to Symptomatic Skeletal-Related Event (TTSSRE)
3. Time to Prostate-specific Antigen (PSA) Progression
4. 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
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
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)
7. Prostate-specific Antigen (PSA) Response Rate
8. Prostate-specific antigen (PSA) Undetectable Rate
9. 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
10. 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
11. Number of Participants Who Experience an Adverse Event (AE)
12. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Yingjie Liu

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Yingjie Liu

Third parties 7

Locations

3 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications