Resumen

Este ensayo clínico de fase III, global, multicéntrico, abierto, aleatorizado y controlado evaluará la eficacia y seguridad de atezolizumab (un anticuerpo anti-ligando de muerte programada 1 [anti-PD-L1]) en comparación con un régimen de quimioterapia con agente único a elección del investigador (vinorelbina o gemcitabina) en participantes sin tratamiento previo con cáncer de pulmón de células no pequeñas (CPCNP) localmente avanzado o metastásico que se consideran no aptos para cualquier quimioterapia con doblete de platino debido a un estado funcional deficiente (estado funcional del Eastern Cooperative Oncology Group [ECOG] de 2-3).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 7th edition
No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected
No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition
Life expectancy greater than or equal to (\>/=) 8 weeks
Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to poor performance status (ECOG performance status of 2-3). However, participants \>= 70 years of age who have an ECOG PS of 0 or 1 may be included due to: a) substantial comorbidities; b) contraindication(s) for any platinum-doublet chemotherapy
Representative formalin-fixed paraffin-embedded (FPPE) tumor tissue block obtained during course of disease (archival tissue) or at screening
Participants with treated, asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: Measurable disease outside CNS; Only supratentorial and cerebellar metastases allowed; No ongoing requirement for corticosteroids as therapy for CNS disease; No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization; No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
Adequate hematologic and end organ function
Female participants of childbearing potential randomized to the atezolizumab treatment arm agree to use protocol defined methods of contraception

Criterios de exclusión

Participants younger than 70 years who have an ECOG performance status of 0 or 1
Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation of the brain during screening and prior radiographic assessments
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Uncontrolled or symptomatic hyerpcalcemia (ionized calcium \> 1.5 mmol/L or calcium \>12 mg/dL or corrected serum calcium \>ULN)
History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (v4.0) Grade 3 or higher toxicities due to any prior therapy (example \[e.g.\], radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication
Participants who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy
History of autoimmune disease except autoimmune-related hypothyroidism and controlled Type I diabetes mellitus
History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
Known positivity for human immunodeficiency virus (HIV)
Known active hepatitis B or hepatitis C
Active tuberculosis
Severe infections within 4 weeks prior to randomization
Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina
Major surgical procedure other than for diagnosis within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study
Prior allogeneic bone marrow transplantation or solid organ transplant
Participants with an illness or condition that may interfere with capacity or compliance with the study protocol, as per investigator's judgment
Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to randomization
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
Oral or IV antibiotic treatment
Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to randomization
Treatment with systemic corticosteroids or other immunosuppressive medications
Participants not willing to stop treatment with traditional herbal medicines
Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that is \[i.e.\] vinorelbine, oral or intravenous, and gemcitabine, intravenous)

Intervenciones

drug

Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Atezolizumab will be administered via IV infusion once every three weeks (QW3).

drug

Vinorelbine

Vinorelbine will be administered per relevant local guidelines and Summary of Product Characteristics (SmPC) management.

drug

Gemcitabine

Gemcitabine will be administered per relevant local guidelines and SmPC management.

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Vinorelbine

Gemcitabine

Ubicaciones

Fundación CENIT para la Investigación en Neurociencias

Hospital Privado de Comunidad

Clinica Viedma S.A.

Patrocinadores