Resumen

El propósito de este estudio es evaluar la seguridad y eficacia a largo plazo de pembrolizumab (MK-3475) en participantes provenientes de estudios parentales previos de Merck basados en pembrolizumab que se incorporan a este estudio de extensión. Este estudio constará de tres fases: 1) Fase de Primer Curso, 2) Fase de Seguimiento de Supervivencia o 3) Fase de Segundo Curso. Cada participante se incorporará a este estudio de extensión en una de las siguientes tres fases, según la fase del estudio en que se encontrara al completar el estudio parental. Los participantes que se encontraban en la Fase de Primer Curso de tratamiento con pembrolizumab o lenvatinib en su estudio parental ingresarán a la Fase de Primer Curso de este estudio y completarán hasta 35 dosis o más cada 3 semanas (Q3W) o 17 dosis o más cada 6 semanas (Q6W) de tratamiento con pembrolizumab, una combinación basada en pembrolizumab o lenvatinib según la asignación de brazo. Los participantes que se encontraban en la Fase de Seguimiento en el estudio parental (posttratamiento o Fase de Seguimiento de Supervivencia) ingresarán a la Fase de Seguimiento de Supervivencia de este estudio. Los participantes que se encontraban en la Fase de Segundo Curso en su estudio parental ingresarán a la Fase de Segundo Curso de este estudio y completarán hasta 17 dosis Q3W o 8 dosis Q6W de tratamiento con pembrolizumab o una combinación basada en pembrolizumab según la asignación de brazo. Cualquier participante proveniente de un ensayo parental en el que se permitiera el cruce a pembrolizumab ante la progresión de la enfermedad podrá ser elegible para 35 dosis en Q3W o 17 dosis en Q6W de pembrolizumab (aproximadamente 2 años), si progresa mientras recibe el brazo de control y pembrolizumab está aprobado para la indicación en el país donde se evalúa al potencial participante elegible para el cruce.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Treated on the parent pembrolizumab studies established by the Sponsor as MK-3475-587 ready.
Currently receiving pembrolizumab, pembrolizumab based combinations or lenvatinib from parent studies or in a follow-up phase.
Additional eligibility criteria for participants who enter Second Course Phase once they are enrolled on MK-3475-587:
Has not received any anticancer systemic treatment since the last dose of pembrolizumab or a pembrolizumab-based combination in First Course Phase.
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Demonstrates adequate organ function.
Have resolution of any toxic effect(s) of First Course Phase trial treatment with pembrolizumab or a pembrolizumab-based combination to Grade 1 or less (except alopecia) before trial treatment in Second Course Phase is started. If participant received major surgery or radiation therapy of \>30 Gray (Gy), they must have recovered from the toxicity and/or complications of the intervention.
A female participant is eligible to enroll if she is not pregnant, not breastfeeding, and ≥1 of the following conditions applies: A woman of childbearing potential (WOCBP) who agrees to use contraception during the study treatment period and for ≥120 days (corresponding to time needed to eliminate any study combination treatment(s) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity.
Additional eligibility criteria for participants who enter dosing with Lenvatinib:
Adequately controlled blood pressure (BP) to \<150/90 mmHg, with or without antihypertensive medications.
For male agrees to be abstinent from penile-vaginal intercourse OR agrees to use a highly effective contraceptive method while receiving study drug and for 7 days after the last dose of lenvatinib.
Is female and not pregnant/breastfeeding and at least one of the following applies during the study and for ≥4 days after: is not a woman of childbearing potential (WOCBP), is a WOCBP and uses highly effective contraception (low user dependency method OR a user dependent hormonal method in combination with a barrier method) or is a WOCBP who is abstinent from heterosexual intercourse.

Criterios de exclusión

Participants are excluded from entering Second Course trial treatment once they are enrolled on MK-3475-587 if any of the following criteria applies:
Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
Has received a live vaccine within 30 days prior to the first dose of Second Course Phase trial treatment.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the Cycle 1 Day 1 of Second Course Phase.
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, melanoma (non-ulcerated, thin primary), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
Has known active central nervous system metastases and/or carcinomatous meningitis.
Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Note: Participants that experienced pneumonitis during First Course that did not meet the criteria for permanent discontinuation are eligible.
Non-small cell lung cancer (NSCLC) participants only: Has interstitial lung disease.
Has an active infection requiring systemic therapy.
Has a known history of human immunodeficiency virus (HIV) infection.
Has a known history of or is positive for hepatitis B or hepatitis C. For parent studies where inclusion of participants with hepatitis was permitted, MK-3475-587 will follow the parent study eligibility criteria for hepatitis.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Second Course Phase eligibility Visit through 120 days after the last dose of study treatment.
Has severe cardiovascular disease, i.e., arrhythmias, requiring chronic treatment, congestive heart failure (New York Heart Association Class III or IV) or symptomatic ischemic heart disease.
Has hepatic decompensation (Child-Pugh score \>6 \[class B and C\]).
Has uncontrolled thyroid dysfunction.
Has uncontrolled diabetes mellitus.
Has had an allogeneic tissue/solid organ transplant.
Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
Has had major surgery within 3 weeks prior to first dose of study intervention(s).
Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
Has urine protein ≥1 g/24 hours.
Has LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.
Prolongation of QT intervals corrected for heart rate using Fridericia's (cube root) correction (QTcF) interval to \>480 ms.
Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.
Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
Has a history of any contraindication or has a severe hypersensitivity to any components of lenvatinib.

Ubicaciones

Centro de Oncología e Investigación de Buenos Aires ( Site 1357)

Berazategui, Buenos Aires, Argentina

Study Coordinator · 541142563156

RECRUITING

Centro de Educación Médica e Investigaciones clínicas "Dr. Norberto Quirno" (CEMIC) ( Site 1368)

Buenos Aires., Buenos Aires, Argentina

Study Coordinator · +54-911-36115955

RECRUITING

Fundacion Favaloro ( Site 1367)

CABA, Buenos Aires, Argentina

Study Coordinator · (54-11) 4378-1200

RECRUITING

Derma Internacional SA ( Site 1372)

CABA, Buenos Aires, Argentina

Study Coordinator · 01168192023

RECRUITING

Instituto Alexander Fleming ( Site 1364)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Study Coordinator · +54-911-36115955

RECRUITING

IDIM - Instituto de Investigaciones Metabólicas ( Site 1362)

Ciudad de Buenos Aires, Buenos Aires, Argentina

Study Coordinator · 541150319700

RECRUITING

Instituto de Investigaciones Clínicas Mar del Plata ( Site 1363)

Mar del Plata, Buenos Aires, Argentina

Study Coordinator · +54-911-36115955

RECRUITING

Instituto Médico Río Cuarto ( Site 1375)

Río Cuarto, Córdoba Province, Argentina

Study Coordinator · +5493585628491

RECRUITING

Clinica Viedma ( Site 1353)

Viedma, Río Negro Province, Argentina

Study Coordinator · +542920432720

RECRUITING

Fundacion Estudios Clinicos ( Site 1369)

Rosario, Santa Fe Province, Argentina

Study Coordinator · +543412384171

RECRUITING

Sanatorio Parque ( Site 1355)

Rosario, Santa Fe Province, Argentina

Study Coordinator · 543414268409

RECRUITING

Instituto de Oncologia de Rosario ( Site 1350)

Rosario, Santa Fe Province, Argentina

Study Coordinator · 5493415778394

RECRUITING

Hospital Provincial del Centenario ( Site 1359)

Rosario, Santa Fe Province, Argentina

Study Coordinator · 0341 430-7185

RECRUITING

Hospital Aleman-Oncology ( Site 1351)

Buenos Aires, Argentina

Study Coordinator · 541148277000

RECRUITING

Clínica Universitaria Reina Fabiola ( Site 1376)

Córdoba, Argentina

Study Coordinator · +5435196778868

RECRUITING

Centro Medico Privado CEMAIC ( Site 1371)

Córdoba, Argentina

Study Coordinator · +5493513717344

RECRUITING

Hospital Privado Universitario de Córdoba ( Site 1354)

Córdoba, Argentina

COMPLETED

Fundación CORI para la Investigación y Prevención del Cáncer ( Site 1358)

La Rioja, Argentina

Study Coordinator · +54-380-443-6443

RECRUITING

Instituto San Marcos ( Site 1366)

San Juan, Argentina

Study Coordinator · (0264) 4222935

RECRUITING

Centro Medico San Roque-Oncology ( Site 1352)

San Miguel de Tucumán, Argentina

Study Coordinator · 5493815000953

RECRUITING

Centro Oncologico Norte. ( Site 1370)

Santiago del Estero, Argentina

Study Coordinator · +543854754816

RECRUITING

Estudio Multicéntrico, Abierto, de Fase 3, para Evaluar la Seguridad y Eficacia a Largo Plazo en Participantes que Actualmente Reciben Tratamiento o se Encuentran en Seguimiento en Estudios que Incluyen Pembrolizumab

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

Standard of Care (SOC)

Lenvatinib

Olaparib

MK-4280

MK-4280A

Ubicaciones

Centro de Oncología e Investigación de Buenos Aires ( Site 1357)

Centro de Educación Médica e Investigaciones clínicas "Dr. Norberto Quirno" (CEMIC) ( Site 1368)

Fundacion Favaloro ( Site 1367)

Derma Internacional SA ( Site 1372)

Instituto Alexander Fleming ( Site 1364)

IDIM - Instituto de Investigaciones Metabólicas ( Site 1362)

Instituto de Investigaciones Clínicas Mar del Plata ( Site 1363)

Instituto Médico Río Cuarto ( Site 1375)

Clinica Viedma ( Site 1353)

Fundacion Estudios Clinicos ( Site 1369)

Sanatorio Parque ( Site 1355)

Instituto de Oncologia de Rosario ( Site 1350)

Hospital Provincial del Centenario ( Site 1359)

Hospital Aleman-Oncology ( Site 1351)

Clínica Universitaria Reina Fabiola ( Site 1376)

Centro Medico Privado CEMAIC ( Site 1371)

Hospital Privado Universitario de Córdoba ( Site 1354)

Fundación CORI para la Investigación y Prevención del Cáncer ( Site 1358)

Instituto San Marcos ( Site 1366)

Centro Medico San Roque-Oncology ( Site 1352)

Centro Oncologico Norte. ( Site 1370)

Patrocinadores

Contactos

Toll Free Number