Resumen

Este ensayo evaluará la seguridad y eficacia de pembrolizumab (MK-3475) en combinación con quimioterapia neoadyuvante (NAC) dobleta de platino antes de la cirugía [fase neoadyuvante], seguida de pembrolizumab solo después de la cirugía [fase adyuvante] en participantes con CPNCP resecable en estadio II, IIIA y IIIB resecable (T3-4N2). Las hipótesis primarias del estudio son que el pembrolizumab neoadyuvante (frente a placebo) en combinación con NAC, seguido de cirugía y pembrolizumab adyuvante (frente a placebo), mejorará: 1) la supervivencia libre de eventos (SLE) evaluada por biopsia por patólogo local o por imágenes evaluadas por el investigador utilizando los Criterios de Evaluación de Respuesta en Tumores Sólidos Versión 1.1 (RECIST 1.1); y 2) la supervivencia global (SG).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Have previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) NSCLC.
If male, must agree to use contraception or practice abstinence as well as refrain from donating sperm during the treatment period and for the time needed to eliminate each study intervention after the last dose of study intervention.
If female, may participate if not pregnant or breastfeeding, and at least one of the following conditions apply: 1) not a woman of childbearing potential (WOCBP); or 2) a WOCBP who agrees to follow contraceptive guidance during the treatment period and for the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
Have available formalin-fixed paraffin embedded (FFPE) tumor tissue sample blocks for submission. If blocks are not available, have unstained slides for submission for central programmed death-ligand 1 (PD-L1) testing.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days of randomization.
Have adequate organ function.

Criterios de exclusión

Has one of the following tumor locations/types:1) NSCLC involving the superior sulcus; 2) Large cell neuro-endocrine cancer (LCNEC); or 3) Sarcomatoid tumor.
Has a history of (non-infectious) pneumonitis /interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease that requires steroids.
Has an active infection requiring systemic therapy.
Has had an allogenic tissue/sold organ transplant.
Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients.
Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents and/or to any of their excipients.
Has an active autoimmune disease that has required systemic treatment in past 2 years.
Has a known history of human immunodeficiency virus (HIV) infection.
Has a known history of Hepatitis B or Hepatitis C.
Has a known history of active tuberculosis.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate.
Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor.
Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy prior to randomization/allocation.
Has received prior radiotherapy within 2 weeks of start of trial treatment.
Has received a live vaccine within 30 days prior to the first dose of trial drug.
Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
Has a diagnosis of immunodeficiency or is receiving either systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.
Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.

Intervenciones

biological

Pembrolizumab

200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1.

drug

Placebo

Normal saline by IV infusion Q3W, given on cycle day 1.

drug

Cisplatin

75 mg/m\^2 by IV infusion Q3W, given on cycle day 1.

drug

Gemcitabine

1000 mg/m\^2 by IV infusion Q3W, given on cycle days 1 and 8. Given only to participants with squamous NSCLC.

drug

Pemetrexed

500 mg/m\^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.

Ubicaciones

Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0136)

Berazategui, Buenos Aires, Argentina

Hospital Privado de Comunidad. ( Site 0130)

Mar del Plata, Buenos Aires, Argentina

Hospital Universitario Austral ( Site 0127)

Pilar, Buenos Aires, Argentina

Fundacion Favaloro ( Site 0128)

Ciudad de Buenos Aires, Buenos Aires F.D., Argentina

Sanatorio Britanico ( Site 0125)

Rosario, Santa Fe Province, Argentina

Sanatorio Parque ( Site 0135)

Rosario, Santa Fe Province, Argentina

Hospital Provincial del Centenario ( Site 0131)

Rosario, Santa Fe Province, Argentina

Hospital Privado Universitario de Córdoba ( Site 0139)

Córdoba, Argentina

Sanatorio Allende ( Site 0129)

Córdoba, Argentina

CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0133)

San Juan, Argentina

Ensayo de fase III, aleatorizado, doble ciego, de quimioterapia dobleta de platino +/- pembrolizumab (MK-3475) como terapia neoadyuvante/adyuvante en participantes con cáncer de pulmón de células no pequeñas (CPNCP) resecable en estadio II, IIIA y IIIB resecable (T3-4N2) (KEYNOTE-671)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

Placebo

Cisplatin

Gemcitabine

Pemetrexed

Ubicaciones

Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0136)

Hospital Privado de Comunidad. ( Site 0130)

Hospital Universitario Austral ( Site 0127)

Fundacion Favaloro ( Site 0128)

Sanatorio Britanico ( Site 0125)

Sanatorio Parque ( Site 0135)

Hospital Provincial del Centenario ( Site 0131)

Hospital Privado Universitario de Córdoba ( Site 0139)

Sanatorio Allende ( Site 0129)

CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0133)

Patrocinadores