Resumen

Este es un estudio de fase 3 de pembrolizumab en combinación con carboplatino/taxano (paclitaxel o nab-paclitaxel) seguido de pembrolizumab con o sin sacituzumab tirumotecán de mantenimiento (sac-TMT; MK-2870) en el tratamiento de primera línea del cáncer de pulmón de células no pequeñas (CPCNP) escamoso metastásico. Se plantea la hipótesis de que pembrolizumab con sacituzumab tirumotecán de mantenimiento es superior a pembrolizumab sin mantenimiento con sacituzumab tirumotecán en cuanto a la supervivencia global (SG).

Descripción detallada

Todos los participantes atraviesan una fase de inducción inicial de cuatro ciclos, cada ciclo compuesto por pembrolizumab cada 3 semanas + carboplatino cada 3 semanas + paclitaxel cada 3 semanas o nab-paclitaxel semanal. Posteriormente, los participantes son asignados aleatoriamente a mantenimiento con pembrolizumab versus mantenimiento con pembrolizumab + sac-TMT.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Histologically or cytologically confirmed diagnosis of squamous non-small cell lung cancer (NSCLC) \[Stage IV: M1a, M1b, M1c, American Joint Committee on Cancer Staging Manual, version 8\]
Measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 as assessed by the local site investigator/radiology
Has life expectancy ≥3 months
Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 assessed within 7 days prior to allocation
Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
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 allocation
Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible)
Has adequate organ function
For Maintenance only (prior to randomization): is without disease progression of their NSCLC, as determined by BICR using RECIST 1.1 after completion of study-specified Induction with an evaluable scan at Week 12 or most recent scan before randomization
For Maintenance only (prior to randomization): has ECOG PS of 0 or 1 as assessed at the Prerandomization Visit
For Maintenance only (prior to randomization): all AEs (with the exception of alopecia, Grade ≤2 fatigue, Grade ≤2 peripheral neuropathy, and Grade ≤2 endocrine-related AEs requiring treatment or hormone replacement) have recovered

Criterios de exclusión

Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>480 ms, and other serious cardiovascular and cerebrovascular diseases within 6 months before study intervention
HIV-infected participants who have been newly diagnosed or with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
Received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as a part of neoadjuvant or adjuvant therapy or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC
Received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T lymphocyte-associated protein 4, OX-40, CD137). Note: Prior treatment with an anti-PD-1 or anti-PD-L1 agent for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC
Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antidrug conjugate (ADC)
Received radiation therapy to the lung that is \>30 Gray within 6 months of start of study intervention
Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
Participants who have not adequately recovered from major surgery or have ongoing surgical complications
Received prior treatment with a topoisomerase I inhibitor-containing ADC
Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study (the required washout period before starting sac-TMT is 2 weeks)
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Has known central nervous system (CNS) metastases/carcinomatous meningitis
Severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients or to another biologic therapy
Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapy \[eg, thyroxine, insulin, or physiologic corticosteroid\] is allowed)
History of (noninfectious)pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
Active infection requiring systemic therapy
History of allogeneic tissue/solid organ transplant

Intervenciones

biological

Pembrolizumab

Intravenous (IV) infusion

biological

sac-TMT

IV infusion

drug

Carboplatin

Participants receive AUC 6 or AUC 5 mg/mL/min IV infusion on Day 1 of each 21-day cycle for 4 cycles as background therapy during the study.

drug

Paclitaxel

Participants receive 200 mg/m\^2 or 175 mg/m\^2 IV infusion on Day 1 of each 21-day cycle for 4 cycles as background therapy during the study.

drug

Nab-paclitaxel

Participants receive 100 mg/m\^2 IV infusion on Days 1, 8 and 15 of each 21-day cycle for 4 cycles as background therapy during the study.

Ubicaciones

Instituto Alexander Fleming ( Site 0203)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Study Coordinator · 3221 8900 int 8123

RECRUITING

Instituto de Investigaciones Clínicas Mar del Plata ( Site 0200)

Mar del Plata, Buenos Aires, Argentina

Study Coordinator · 0223 496-3224

RECRUITING

Instituto Médico Río Cuarto ( Site 0204)

Río Cuarto, Córdoba Province, Argentina

Study Coordinator · +543584679361

RECRUITING

Fundacion Intecnus ( Site 0205)

Bariloche, Río Negro Province, Argentina

Study Coordinator · 0294 474-6050

RECRUITING

Sanatorio Parque ( Site 0201)

Rosario, Santa Fe Province, Argentina

Study Coordinator · 0341 420-0222

RECRUITING

Hospital Aleman-Oncology ( Site 0202)

Buenos Aires, Argentina

Study Coordinator · +54 11 4827-7000

RECRUITING

Estudio de Fase 3 de Pembrolizumab en Combinación con Carboplatino/Taxano (Paclitaxel o Nab-paclitaxel) Seguido de Pembrolizumab con o sin Mantenimiento con MK-2870 en el Tratamiento de Primera Línea del Cáncer de Pulmón de Células no Pequeñas Escamoso Metastásico

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

sac-TMT

Carboplatin

Paclitaxel

Nab-paclitaxel

Ubicaciones

Instituto Alexander Fleming ( Site 0203)

Instituto de Investigaciones Clínicas Mar del Plata ( Site 0200)

Instituto Médico Río Cuarto ( Site 0204)

Fundacion Intecnus ( Site 0205)

Sanatorio Parque ( Site 0201)

Hospital Aleman-Oncology ( Site 0202)

Patrocinadores

Contactos

Toll Free Number