Resumen

El propósito de este estudio es evaluar la eficacia y seguridad de la combinación de pembrolizumab (MK-3475) y enzalutamida en el tratamiento de hombres con cáncer de próstata metastásico resistente a la castración (CPRCm) que no han recibido quimioterapia para el CPRCm, son vírgenes de abiraterona o son intolerantes o han progresado con acetato de abiraterona. Existen dos hipótesis primarias del estudio. Hipótesis 1: La combinación de pembrolizumab más enzalutamida es superior a placebo más enzalutamida en cuanto a la Supervivencia Global (SG). Hipótesis 2: La combinación de pembrolizumab más enzalutamida es superior a placebo más enzalutamida en cuanto a la Supervivencia Libre de Progresión Radiográfica (SLPr) según los Criterios de Evaluación de Respuesta en Tumores Sólidos Versión 1.1 (RECIST 1.1) modificados por el Grupo de Trabajo en Cáncer de Próstata (PCWG), evaluados por revisión central independiente ciega.

Elegibilidad

Edad mínima: 18 YearsSexo: MALE

Criterios de inclusión

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 randomization
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 met one of the following criteria with regard to abiraterone acetate exposure: (1) is abiraterone-naïve; (2) received prior abiraterone acetate for the treatment of mHSPC or mCRPC, for a minimum of 4 weeks and not progressed while on treatment; or (3) received prior abiraterone acetate for the treatment of mHSPC or mCRPC and progressed on treatment after a minimum of 8 weeks treatment (minimum 14 weeks for those with bone progression)
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 90 days after the last dose of enzalutamide: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom
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

Criterios de exclusión

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 (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
Has known active human immunodeficiency virus (HIV), concurrent active hepatitis B virus (HBV) or known active hepatitis C virus (HCV) infection
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
Has a history of seizure or any condition that may predispose to seizure
Has a history of loss of consciousness within 12 months of screening
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
Has bradycardia (heart rate of \<50 beats per minute) on the screening electrocardiogram (ECG)
Has history of prostate cancer progression on ketoconazole
Has had prior treatment with enzalutamide, apalutamide, darolutamide or cytochrome P450 (CYP) 17 inhibitor other than abiraterone acetate
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
Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC
Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization
Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto) prior to randomization
Has received a live or live attenuated vaccine within 30 days prior to randomization
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 90 days after the last dose of enzalutamide
Has had an allogenic tissue/solid organ transplant

Ubicaciones

Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1013)

Berazategui, Buenos Aires, Argentina

Organizacion Medica de Investigacion ( Site 1019)

CABA, Buenos Aires, Argentina

Instituto Medico Alexander Fleming ( Site 1010)

Ciudad Autonoma de Buenos Aires., Buenos Aires, Argentina

Instituto de Investigaciones Clinicas ( Site 1000)

Mar del Plata, Buenos Aires, Argentina

Centro de Diagnostico Urologico ( Site 1008)

Buenos Aires, Buenos Aires F.D., Argentina

Sanatorio Parque ( Site 1002)

Rosario, Santa Fe Province, Argentina

Instituto de Oncologia de Rosario ( Site 1015)

Rosario, Santa Fe Province, Argentina

Instituto de Investigaciones Metabolicas [Buenos Aires, Argentina] ( Site 1011)

Buenos Aires, Argentina

Hospital Aleman ( Site 1004)

Buenos Aires, Argentina

Centro Medico Dra De Salvo ( Site 1018)

Buenos Aires, Argentina

CEMAIC ( Site 1014)

Córdoba, Argentina

Centro Oncologico Riojano Integral ( Site 1005)

La Rioja, Argentina

Centro Oncologico de Integracion Regional. COIR ( Site 1007)

Mendoza, Argentina

Ensayo de fase 3, aleatorizado, doble ciego de pembrolizumab (MK-3475) más enzalutamida versus placebo más enzalutamida en participantes con cáncer de próstata metastásico resistente a la castración (CPRCm) (KEYNOTE-641)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

Enzalutamide

Placebo

Ubicaciones

Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1013)

Organizacion Medica de Investigacion ( Site 1019)

Instituto Medico Alexander Fleming ( Site 1010)

Instituto de Investigaciones Clinicas ( Site 1000)

Centro de Diagnostico Urologico ( Site 1008)

Sanatorio Parque ( Site 1002)

Instituto de Oncologia de Rosario ( Site 1015)

Instituto de Investigaciones Metabolicas [Buenos Aires, Argentina] ( Site 1011)

Hospital Aleman ( Site 1004)

Centro Medico Dra De Salvo ( Site 1018)

CEMAIC ( Site 1014)

Centro Oncologico Riojano Integral ( Site 1005)

Centro Oncologico de Integracion Regional. COIR ( Site 1007)

Patrocinadores