A clinical trial comparing a new treatment (MK-5684) to approved medication for advanced prostate cancer after prior hormonal therapy and chemotherapy

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

4 Apr 2024 → ongoing

Decision date (initial)

2024-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC · Orion Corporation

External identifiers

EU CT number

2023-504899-25-00

WHO UTN

U1111-1287-5304

ClinicalTrials.gov

NCT06136624

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Therapy, Pharmacokinetic, Efficacy, Pharmacodynamic, Safety, Pharmacogenomic

1. To compare MK-5684 to alternative abiraterone acetate or enzalutamide with respect to overall survival in participants with mCRPC.

Secondary objectives 7

1. To evaluate rPFS per PCWG Modified RECIST 1.1 as assessed by BICR in participants with mCRPC.
2. To evaluate the TFST of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide
3. To evaluate the OR and DOR per PCWG Modified RECIST 1.1 as assessed by BICR of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.
4. To evaluate the Time to Pain Progression (TTPP) of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.
5. To evaluate the time to PSA progression of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.
6. To evaluate the time to first SSRE of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.
7. To evaluate the safety and tolerability of MK-5684.

Conditions and MedDRA coding

Metastatic castration resistant prostate cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
2. Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months before Screening
3. If participant received first generation anti-androgen therapy before screening, the participant has evidence of disease progression >4 weeks since the last flutamide treatment and >6 weeks since the last bicalutamide or nilutamide treatment
4. 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)
5. Has disease that progressed during or after treatment with 1 novel hormonal agent (NHA)
6. Has received 1 but no more than 2 taxane-based chemotherapy regimens for metastatic castration-resistant prostate cancer (mCRPC) and has had progressive disease (PD) during or after treatment
7. Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM)
8. Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for ≥ 4 weeks before the date of randomization
9. If capable of producing sperm, participant must agree to the following during the study treatment period and for at least 7 days after the last dose of MK-5684, for at least 30 days after the last dose of abiraterone acetate, and for at least 3 months after the last dose of enzalutamide: EITHER be abstinent OR must agree to use male condom.
10. Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated
11. Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
12. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization
13. Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization.
14. Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at Screening.
15. Has had prior treatment with poly (ADP-ribose) polymerase inhibitor (PARPi) or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment
16. Has received prior 177Lu-prostate-specific membrane antigen (PSMA)-617 or were deemed ineligible to receive 177Lu-PSMA-617 treatment by the investigator or refused 177Lu-PSMA-617 treatment
17. Participants who have not received cabazitaxel can be enrolled if they are ineligible for cabazitaxel treatment as determined by the investigator or have refused treatment

Exclusion criteria 33

1. Has a gastrointestinal disorder that might affect absorption
2. Unable to swallow capsules/tablets
3. History of pituitary dysfunction
4. Poorly controlled diabetes mellitus
5. Clinically significant abnormal serum potassium or sodium level
6. Has a history of active or unstable cardio/cerebro-vascular disease, including thromboembolic events
7. Has a history of seizure within 6 months of providing documented informed consent or any condition that may predispose to seizures within 12 months before the date of randomization
8. Has a history of clinically significant ventricular arrhythmias
9. Has received an anticancer monoclonal antibody (mAb) within 4 weeks before the date of randomization, or has not recovered from adverse events (AEs) due to mAbs administered more than 4 weeks before the date of randomization
10. Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 28 days before the date of randomization, and has not recovered from the toxicities and/or complications
11. Participants who have not adequately recovered from major surgery or have ongoing surgical complications
12. Has used herbal or medicinal products that may have hormonal anti-prostate cancer activity and/or are known to decrease prostate-specific Antigen (PSA) (eg, saw palmetto, megesterol acetate) within 4 weeks before the date of randomization
13. Has received radium-223 or lutetium-177 within 4 weeks before the date of randomization, or has not recovered to Grade ≤1 or baseline from AEs due to radium-223 or lutetium-177 administered more than 4 weeks before the date of randomization
14. Is currently being treated with cytochrome 450-inducing antiepileptic drugs for seizures
15. Has received treatment with 5-αreductase inhibitors (eg, finasteride or dutasteride), estrogens, or cyproterone within 4 weeks before the date of randomization
16. Use of aldosterone antagonist (eg, spironolactone, eplerenone) and phenytoin within 4 weeks before the start of the study intervention
17. Participants on an unstable dose of thyroid hormone therapy within 6 months before the start of the study intervention
18. Has received colony-stimulating factors within 28 days before the date of randomization
19. Has received a whole blood transfusion in the last 120 days before the date of randomization. Packed red blood cells and platelet transfusions are acceptable if not given within 28 days of the date of randomization.
20. Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention as follows: enzalutamide or apalutamide within 3 weeks or abiraterone acetate + prednisone or darolutamide within 2 weeks
21. Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
22. Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
23. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
24. Has a “superscan” bone scan
25. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
26. Known additional malignancy that is progressing or has required active treatment within the past 3 years
27. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
28. Has an active autoimmune disease that has required systemic treatment in past 2 years
29. Has an active infection requiring systemic therapy
30. Has concurrent active HBV or known active HCV infection
31. Has a history of long QTc syndrome
32. Has any of the following at Screening Visit: hypotension (systolic blood pressure [BP] <110 mm Hg) or uncontrolled hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥90 mm Hg, in 2 out of 3 recordings with optimized antihypertensive therapy)
33. Systemic use of the following medications within 2 weeks before the first dose of study intervention: strong CYP3A4 inducers (eg, avasimibe,carbamazepine, lumacaftor, phenobarbital, rifampicin, rifapentine, or St John's Wort); P-gp inhibitors (eg, erythromycin, clarithromycin,rifampicin, ketoconazole, itraconazole, posaconazole, artesunate-pyronaridine, ritonavir, indinavir, nelfi navir, atazanavir, glecaprevir-pibrentasvir,simeprevir, ledipasvir-sofosbuvir, verapamil, diltiazem, dronedarone, propafenone, quinidine, cyclosporine, valspodar, or milk thistle [Silybummarianum])

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall Survival (OS) in Androgen Receptor Ligand Binding Domain (AR LBD) mutation-positive participants
2. OS in AR LBD mutation-negative participants

Secondary endpoints 10

1. Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review in AR LBD mutation-positive participants
2. rPFS Per Prostate Cancer Working Group-modified RECIST 1.1 as Assessed by Blinded Independent Central Review in AR LBD mutation-negative participants
3. Time to Initiation of the First Subsequent Anti-Cancer Therapy or Death (TFST)
4. Objective Response (OR) 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
5. Duration of Response (DOR) Per PCWG-modified RECIST 1.1 as Assessed by Blinded Independent Central Review
6. 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)
7. Time to Prostate-specific Antigen (PSA) Progression
8. Time to First Symptomatic Skeletal-related Event (SSRE)
9. Number of Participants Who Experience an Adverse Event
10. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event

Investigational products

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

Test 1

Comparator 6

Auxiliary 8

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

Charles Schloss

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Charles Schloss

Third parties 7

Locations

14 EU/EEA countries · 68 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 12 · Art. 38 CTR

Results and documents

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

Documents 104 files

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

Application history

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