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JOURNAL ONKOLOGIE – STUDIE

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365)

Rekrutierend

NCT-Nummer:
NCT02861573

Studienbeginn:
November 2016

Letztes Update:
22.04.2024

Wirkstoff:
Pembrolizumab 200 mg, Olaparib 400 mg, Docetaxel 75 mg/m^2, Prednisone 5 mg, Enzalutamide 160 mg, Olaparib 300 mg, Abiraterone acetate 1000 mg, Lenvatinib, Pembrolizumab/Vibostolimab coformulation, Carboplatin, Etoposide, Belzutifan 120mg

Indikation (Clinical Trials):
Prostatic Neoplasms

Geschlecht:
Männer

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Merck Sharp & Dohme LLC

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(3 von 34)

Call for Information (Investigational Site 2086)
90073 Los Angeles
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 0007)
92868 Orange
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 2041)
80045 Aurora
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 2018)
20007 Washington
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 0010)
60607 Chicago
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 2083)
21201 Baltimore
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 0004)
27518 Cary
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 2091)
44195 Cleveland
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 2027)
97239 Portland
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 2094)
97239 Portland
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 0008)
15232 Pittsburgh
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 2065)
29401 Charleston
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 2090)
38138 Germantown
United StatesRekrutierend» Google-Maps
Call for Information (Investigational Site 0016)
98109 Seattle
United StatesRekrutierend» Google-Maps
Merck Canada
H9H 4M7 Kirkland
CanadaRekrutierend» Google-Maps
Ansprechpartner:
Medical Information Centre Centre d'information medicale Merck Canada Inc.
Phone: 514-428-8600 / 1-800-567-2594» Ansprechpartner anzeigen
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Studien-Informationen

Detailed Description:

Assignment of patients to a cohort will be based on prior treatment as outlined in the

eligibility criteria.

Participants who discontinue pembrolizumab or vibostolimab+pembrolizumab after 35 infusions

for reasons other than disease progression or intolerability, or who discontinue

pembrolizumab or coformulation of pembrolizumab/vibostolimab after attaining a complete

response (and had at least 8 administrations of pembrolizumab or pembrolizumab/vibostolimab

coformulation and at least 2 treatments with pembrolizumab or pembrolizumab/vibostolimab

coformulation beyond initial complete response) may be eligible to receive a second course of

treatment that includes up to 17 additional infusions (approximately 1 year) of pembrolizumab

monotherapy or pembrolizumab/vibostolimab coformulation after they have experienced

radiographic disease progression after stopping first course treatment.

Effective with Protocol Amendment 08, enrollment into Cohorts A, B, C, and D was closed.

Effective with Protocol Amendment 14, enrollment into Cohorts E, F, G, and H was closed (not

due to any safety issues). No further efficacy and survival follow-up assessments will be

collected in Cohorts A through H.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- For Cohorts A, B, C, D, E, G, J: Has histologically- or cytologically-confirmed

adenocarcinoma of the prostate without small cell histology

- For Cohorts F, H, I: Has t-NE or de novo metastatic prostate cancer defined by

≥1% neuroendocrine cells that are located in discrete regions of a recent biopsy

specimen from a metastasis as determined by the investigational site and

confirmed by central histology review prior to enrollment. Epstein criteria of

neuroendocrine differentiation in prostate cancer is used for eligibility.

Specimens must have one of the morphologies of Small cell carcinoma or Large cell

neuroendocrine carcinoma (LCNEC) or Mixed (small or large cell) NE carcinoma -

acinar adenocarcinoma with positive IHC confirmed by central pathology review

- Is able to provide tumor tissue from a site not previously irradiated as follows:

Cohorts A, E, G and J: must provide a core or excisional biopsy from soft tissue or

bone biopsy within 1 year of screening and after developing mCRPC; Cohort B: must

provide an archival tumor tissue sample or tumor tissue from a newly obtained core or

excisional biopsy from soft tissue if the lesion is clinically accessible; Cohorts C

and D with soft tissue disease: must provide a core or excisional biopsy from a soft

tissue lesion if clinically accessible within 1 year of screening and after developing

mCRPC and an archival specimen if available; and Cohorts F, H, and I must provide a

core or excisional biopsy from soft tissue or a bone biopsy. For de novo metastatic

neuroendocrine prostate participants, biopsies must be performed within 1 year of

screening. Participants with bone metastasis only must provide an archival tumor

tissue specimen

- Has prostate cancer progression within 6 months prior to screening, as determined by

the investigator, by means of one of the following: PSA progression as defined by a

minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment

where the PSA value at screening should be ≥2 ng/mL; radiographic disease progression

in soft tissue based on Response Evaluation Criteria In Solid Tumors Version 1.1

criteria with or without PSA progression; radiographic disease progression in bone

defined as the appearance of 2 or more new bone lesions on bone scan with or without

PSA progression. Participants with de novo neuroendocrine prostate cancer will not

need to provide evidence of progression within 6 months

- Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM).

Treatment with luteinizing hormone-releasing hormone agonists or antagonists for all

cohorts must have been initiated ≥4 weeks prior to first dose of study therapy and

must be continued throughout the study. Participants with de novo metastatic NE

prostate cancer will not be required to have been previously treated with androgen

deprivation therapy (ADT). ADT must be started in these participants by the time of

treatment allocation/randomization

- Participants receiving bone resorptive therapy (including, but not limited to

bisphosphonate or receptor activator of nuclear factor kappa-β ligand inhibitor) must

be on stable doses for ≥4 weeks prior to first dose of study therapy

- Must be abstinent from heterosexual intercourse, refrain from donating sperm, or agree

to use contraception (unless confirmed to be azoospermic) during the intervention

period starting with the first dose of study therapy. The length of time required to

continue contraception after the last dose of study intervention for each study

intervention is as follows: 7 days for abiraterone acetate and lenvatinib; 30 days for

enzalutamide; and 95 days for olaparib, docetaxel, and carboplatin/etoposide. No

contraception measures are required during and after the intervention period for

pembrolizumab/vibostolimab coformulation

- Has a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group

(ECOG) Performance Scale for Cohorts A and C and a performance status of 0 or 1 for

Cohorts B, D, E, F, G, H, I and J within 10 days of study start

- For Cohort A: Has received docetaxel for mCRPC. Prior treatment with 1 other

chemotherapy for mCRPC is allowed. Up to 2 second-generation hormonal manipulations

(e.g., abiraterone acetate and/or enzalutamide) are allowed. Prior docetaxel for

metastatic hormone-sensitive prostate cancer is allowed if ≥4 weeks have elapsed from

the last dose of docetaxel prior to day 1 of Cycle 1

- For Cohort B: Has received prior treatment with either abiraterone acetate or

enzalutamide (but not both) in the prechemotherapy mCRPC state. Participants in Cohort

B must have received at least 4 weeks of either abiraterone or enzalutamide treatment

(but not both) who failed treatment or became intolerant of the drug

- For Cohort C: Has received prior treatment with abiraterone acetate in the

pre-chemotherapy mCRPC state without prior enzalutamide. Participants in Cohort C must

have received at least 4 weeks of abiraterone treatment who failed treatment or become

intolerant of the drug. Participants who received abiraterone acetate in the

hormone-sensitive state will not be eligible

- For Cohort D: Has not received chemotherapy for mCRPC and has either not had prior

second generation hormonal manipulation for mCRPC OR has previously been treated with

enzalutamide for mCRPC and failed treatment or has become intolerant of the drug.

Prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if ≥4

weeks have elapsed from the last dose of docetaxel. Prior treatment with abiraterone

acetate in the hormone-sensitive metastatic setting is allowed as long as there was no

progression on this agent and abiraterone acetate was not discontinued due to adverse

events (AEs)

- For Cohorts E, G and J: Has received docetaxel for mCRPC. Prior treatment with 1 other

chemotherapy for mCRPC is allowed. Up to 2 second-generation hormonal manipulations

(eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide or other

next-generation hormonal agents [NHA]) are allowed. Participants who received prior

ketoconazole for metastatic disease may be enrolled. If docetaxel chemotherapy is used

more than once (eg, once for metastatic hormone-sensitive and once for mCRPC), it will

be considered as 1 therapy. Prior docetaxel for metastatic hormone-sensitive prostate

cancer (mHSPC) is allowed if ≥4 weeks have elapsed from the last dose of docetaxel

prior to Day 1 of Cycle 1

- For Cohort F, H, and I: Participants must have received prior treatment with androgen

deprivation therapy (ADT) for metastatic disease. Prior treatment with up to a total

of 2 chemotherapies for mCRPC is allowed, as well as up to 2 second-generation

hormonal manipulations for mCRPC. Participants who received prior ketoconazole for

metastatic disease may be enrolled. Docetaxel for mHSPC is allowed in addition to

docetaxel for mCRPC. If docetaxel chemotherapy is used more than once (eg, once for

metastatic hormone-sensitive and once for mCRPC), it will be considered as 1 therapy

Exclusion Criteria:

- Has had a prior anticancer monoclonal antibody (mAb) within 4 weeks prior to first

dose study therapy or who has not recovered (i.e., Grade ≤1 or at baseline) from AEs

due to mAbs administered >4 weeks earlier

- Has had prior chemotherapy, targeted small molecule therapy abiraterone treatment,

enzalutamide treatment, or radiation therapy within 2 weeks prior to first dose of

study therapy or who has not recovered (ie, Grade ≤1 or at baseline) from AEs due to a

previously administered agent

- Is currently participating in and receiving study therapy or has participated in a

study of an investigational agent and received study drug or used an investigational

device within 4 weeks of treatment allocation/randomization

- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any

other form of immunosuppressive therapy within 7 days prior to treatment

allocation/randomization

- Has had prior treatment with therapeutic radiopharmaceuticals for prostate cancer,

such as Radium-223 or Leutitium-177, within 4 weeks prior to the first dose of trial

treatment

- Has an active autoimmune disease that has required systemic treatment in past 2 years

- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required

steroids or current pneumonitis/interstitial lung disease

- Has previously participated in any other pembrolizumab trial, or received prior

therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death

ligand 1 (anti-PD-L1), and anti-programmed cell death ligand 1 (anti-PD-L2)

- Has a known history of Human Immunodeficiency Virus (HIV)

- Has known active Hepatitis B or Hepatitis C

- Has received a live vaccine or live-attenuated vaccine within 30 days of the first

dose of study therapy

- Has known active central nervous system metastases and/or carcinomatous meningitis

- Has a "superscan" bone scan defined as an intense symmetric activity in the bones and

diminished renal parenchymal activity on baseline bone scan such that the presence of

additional metastases in the future could not be evaluated

- Has had prior solid, organ or bone marrow transplant

- For Cohort A: Has experienced a seizure or seizures within 6 months of study start or

is currently being treated with cytochrome P450 enzyme (CYP) inducing anti-epileptic

drugs for seizures

- For Cohort A: Is currently receiving strong or moderate inhibitors of CYP3A4 including

azole antifungals; macrolide antibiotics; or protease inhibitors

- For Cohort A: Is currently receiving strong or moderate inducers of CYP3A4

- For Cohort A: Has myelodysplastic syndrome

- For Cohort A: Has symptomatic congestive heart failure (New York Heart Association

Class III or IV heart disease), unstable angina pectoris, cardiac arrhythmia, or

uncontrolled hypertension

- For Cohort B: Has received prior treatment with docetaxel or another chemotherapy

agent for metastatic prostate cancer

- For Cohort B: Has peripheral neuropathy Common Terminology Criteria for Adverse Events

≥2 except due to trauma

- For Cohort B: Has ascites and/or clinically significant pleural effusion

- For Cohort B:Has symptomatic congestive heart failure (New York Heart Association

Class III or IV heart disease)

- For Cohort B: Is currently receiving any of the following classes of inhibitors of

CYP3A4: azole antifungals; macrolide antibiotics; or protease inhibitors

- For Cohort C: Has received prior chemotherapy for mCRPC. Prior docetaxel for

metastatic hormone-sensitive prostate cancer is allowed if ≥4 weeks elapsed from last

dose of docetaxel. Participants who received abiraterone acetate in the

hormone-sensitive state will not be eligible

- For Cohort C: Has a history of seizure or any condition that may predispose to seizure

(including, but not limited to prior cerebrovascular accident, transient ischemic

attack, or brain arteriovenous malformation; or intracranial masses such as a

schwannoma or meningioma that is causing edema or mass effect)

- For Cohort C:Has known or suspected brain metastasis or leptomeningeal carcinomatosis

- For Cohort C: Has a history of loss of consciousness within 12 months of the screening

visit

- For Cohort C: 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

- For Cohort C: Has received treatment with 5-α reductase inhibitors (e.g., finasteride,

dutasteride), estrogens, and/or cyproterone within 4 weeks prior to Cycle 1

- For Cohort C: Has a history of prostate cancer progression on ketoconazole

- For Cohort D: Has received prior treatment with docetaxel or another chemotherapy

agent for metastatic prostate cancer

- For Cohort D: Has progressed on prior abiraterone acetate for treatment of castration

sensitive or resistant metastatic prostate cancer

- For Cohort D: Has discontinued prior treatment with abiraterone acetate due to AEs

- For Cohort D: Has previously been treated with ketoconazole for prostate cancer for >7

days

- For Cohort D: Has received prior systemic treatment with an azole drug (eg,

fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1

- For Cohort D: Has uncontrolled hypertension (systolic BP ≥ 160 mm Hg or diastolic BP ≥

95 mm Hg)

- For Cohort D: Has a history of pituitary or adrenal dysfunction

- For Cohort D: Has clinically significant heart disease as evidenced by myocardial

infarction, or arterial thrombotic events in the past 6 months, severe or unstable

angina, or New York Heart Association Class II-IV heart disease or cardiac ejection

fraction measurement of <50% at baseline

- For Cohort D: Has atrial fibrillation, or other cardiac arrhythmia requiring therapy

- For Cohort D: Has a history of chronic liver disease

- For Cohort D: Is currently receiving strong CYP3A4 inducers (eg, phenytoin,

carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during abiraterone

acetate treatment, CYP2D6 substrates with a narrow therapeutic index (for example

thioridazine), or CYP2C8 substrates with a narrow therapeutic index (for example

pioglitazone)

- For Cohorts E and F: Has a left ventricular ejection fraction (LVEF) below the

institutional (or local laboratory) normal range, as determined by multigated

acquisition (MUGA) or echocardiogram (ECHO)

- For Cohorts E and F: Has radiographic evidence of encasement or invasion of a major

blood vessel, or of intratumoral cavitation

- For Cohorts E and F: Has prolongation of QT interval by Fredericia (QTcF) interval to

>480 milliseconds

- For Cohorts E and F: Has had major surgery within 3 weeks prior to first dose of study

interventions

- For Cohorts E and F: Has pre-existing ≥Grade 3 gastrointestinal or

non-gastrointestinal fistula

- For Cohorts E and F: Has had significant cardiovascular impairment within 12 months of

the first dose of study intervention, such as history of New York Heart Association

>Class II congestive heart failure, unstable angina, myocardial infarction, or

cerebrovascular accident (CVA)/stroke, cardiac revascularization procedure, or cardiac

arrhythmia associated with hemodynamic instability

- For Cohorts E and F: Has active hemoptysis (bright red blood of at least 0.5 teaspoon)

within 3 weeks prior to the first dose of lenvatinib

- For Cohorts E and F: Has gastrointestinal malabsorption or any other condition that

might affect the absorption of lenvatinib

- For Cohorts G, H, and I: Has had a severe hypersensitivity reaction to treatment with

another monoclonal antibody

- For Cohorts G, H, and I: Has symptomatic ascites or pleural effusion

- For Cohort I: Has clinically active diverticulitis, intra-abdominal abscess,

gastrointestinal obstruction, and/or abdominal carcinomatosis

- For Cohort I: Has received previous treatment for prostate cancer with

platinum-containing compounds

Studien-Rationale

Primary outcome:

1. Percentage of Participants With a Decrease of ≥50% in Prostatic Specific Antigen (PSA) (Time Frame - From Baseline Measured Every 3 Weeks Until Radiographic Progression Estimated to be Approximately 2 Years)

2. Number of Participants with Adverse Events (AEs) (Time Frame - Assessed Every 3 Weeks Over the Duration of the Study Which is Estimated to be Approximately 2 Years)

3. Number of Participants Discontinuing Study Drug Due to AEs (Time Frame - Assessed Every 3 Weeks Over the Duration of the Study Which is Estimated to be Approximately 2 Years)

4. Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) (Time Frame - Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years)

Secondary outcome:

1. Disease Control Rate (DCR) Based on Prostate Cancer Working Group 3 (PCWG3)-modified RECIST 1.1 Assessed by BICR (Time Frame - Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years)

2. Overall Survival (OS) (Time Frame - Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years)

3. Duration of Response (DOR) Based on PCWG3-modified RECIST 1.1 Assessed by BICR (Time Frame - Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years)

4. ORR Based on PCWG3-modified RECIST 1.1 Assessed by BICR (Time Frame - Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years)

5. Time to PSA Progression (Time Frame - Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years)

6. Radiographic Progression-free Survival (rPFS) Based on PCWG3-modified RECIST 1.1 Assessed by BICR (Time Frame - Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years)

7. Composite Response Rate Defined as Any One of the Following: A. Response Based on RECIST 1.1; B. PSA Decrease of ≥50%; or C. Circulating Tumor-cell Count Conversion (Pembrolizumab + Olaparib Cohort Only) (Time Frame - Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years)

Studien-Arme

  • Experimental: Pembrolizumab+Olaparib
    Participants with adenocarcinoma (AC) mCRPC in Cohort A will receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week dosing cycle (Q3W) and olaparib 400 mg capsules or 300 mg tablets by mouth (PO) twice a day (BID) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with olaparib will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug.
  • Experimental: Pembrolizumab+Docetaxel+Prednisone
    Participants with AC mCRPC in Cohort B will receive pembrolizumab 200 mg IV on Day 1 Q3W, docetaxel 75 mg/m^2 IV on Day 1 Q3W, and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Participants will only be permitted to receive a maximum of 10 cycles of docetaxel and prednisone. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.
  • Experimental: Pembrolizumab+Enzalutamide
    Participants with AC mCRPC in Cohort C will receive pembrolizumab 200 mg IV on Day 1 Q3W and enzalutamide 160 mg PO every day (QD) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with enzalutamide will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug.
  • Experimental: Pembrolizumab+Abiraterone+Prednisone
    Participants with AC mCRPC in Cohort D will receive pembrolizumab 200 mg IV on Day 1 Q3W, abiraterone acetate 1000 mg PO QD and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.
  • Experimental: Pembrolizumab+Lenvatinib: AC
    Participants with AC mCRPC in Cohort E will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.
  • Experimental: Pembrolizumab+Lenvatinib:t-NE
    Participants with neuroendocrine (t-NE) mCRPC in Cohort F will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.
  • Experimental: Pembrolizumab/Vibostolimab coformulation
    Participants with AC mCRPC in Cohort G will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.
  • Experimental: Pembrolizumab/Vibostolimab coformulation:t-NE
    Participants with t-NE mCRPC in Cohort H will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.
  • Experimental: Pembrolizumab+Carboplatin+Etoposide
    Participants with neuroendocrine mCRPC in Cohort I Arm 1 will receive pembrolizumab 200 mg IV on Day 1 Q3W + carboplatin titrated to an area under the plasma drug concentration-time curve [AUC] 5 IV on Day 1 Q3W + etoposide 100 mg/m^2 IV on Days 1, 2, and 3 Q3W. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin+etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 or 2 of the 3 drugs due to adverse events in the combination may continue the study with the other combination drug/drugs.
  • Experimental: Carboplatin+Etoposide
    Participants with neuroendocrine mCRPC in Cohort I Arm 2 will receive carboplatin titrated to an area under the plasma drug concentration-time curve [AUC] 5 IV on Day 1 Q3W + etoposide 100 mg/m^2 IV on Days 1, 2, and 3 Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin+etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.
  • Experimental: Belzutifan
    Participants with AC mCRPC in Cohort J will receive belzutifan 120mg QD in the initial cohort. If an efficacy signal is detected in this arm based on a totality of evidence, Cohort J may be expanded further where participants will be randomized 1:1 to receive either belzutifan 120 mg QD or belzutifan 120 mg QD and pembrolizumab 200 mg Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.
  • Experimental: Pembrolizumab+Belzutifan
    Participants with AC mCRPC in Cohort J will receive belzutifan 120mg QD in the initial cohort. If an efficacy signal is detected in this arm based on a totality of evidence, Cohort J may be expanded further where participants will be randomized 1:1 to receive either belzutifan 120 mg QD or belzutifan 120 mg QD and pembrolizumab 200 mg Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.

Geprüfte Regime

  • Pembrolizumab 200 mg (KEYTRUDA® / MK-3475 / ):
    IV Q3W
  • Olaparib 400 mg (LYNPARZA® / MK-7339 / ):
    Eight 50-mg capsules PO BID
  • Docetaxel 75 mg/m^2 (TAXOTERE®):
    IV Q3W
  • Prednisone 5 mg:
    One 5-mg tablet PO BID
  • Enzalutamide 160 mg (XTANDI®):
    Four 40-mg capsules, four 40-mg tablets, or two 80-mg tablets PO QD
  • Dexamethasone 8 mg:
    Premedication for Cohort B given PO at 12, 3, and 1 hours prior to docetaxel infusion Q3W
  • Olaparib 300 mg (LYNPARZA® / MK-7339 / ):
    Two 150-mg tablets PO BID
  • Abiraterone acetate 1000 mg (ZYTIGA®):
    Two 500-mg or four 250-mg tablets PO QD
  • Lenvatinib (LENVIMA® / MK-7902 / ):
    20 mg PO QD
  • Pembrolizumab/Vibostolimab coformulation (MK-7684A):
    IV Q3W
  • Carboplatin (PARAPLATIN®):
    IV Q3W
  • Etoposide (TOPOSAR™):
    IV on Days 1, 2 and 3 of each cycle
  • Belzutifan 120mg (WELIREG™):
    PO QD

Quelle: ClinicalTrials.gov


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"Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365)"

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