A Study of Atezolizumab in Combination With Carboplatin Plus (+) Paclitaxel With or Without Bevacizumab Compared With Carboplatin+Paclitaxel+Bevacizumab in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower150)

Roche

Status and phase: Completed; Phase 3

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT02366143

2014-003207-30 (EudraCT Number)

GO29436

Details and patient eligibility

About

This randomized, open-label study evaluated the safety and efficacy of atezolizumab (an engineered anti-programmed death-ligand 1 [PD-L1] antibody) in combination with carboplatin+paclitaxel with or without bevacizumab compared with treatment with carboplatin+paclitaxel+bevacizumab in chemotherapy-naïve participants with Stage IV non-squamous NSCLC. Participants were randomized in a 1:1:1 ratio to Arm A (Atezolizumab+Carboplatin+Paclitaxel), Arm B (Atezolizumab+Carboplatin+Paclitaxel+Bevacizumab), or Arm C (Carboplatin+Paclitaxel+Bevacizumab).

Enrollment: 1,202 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group performance status 0 or 1
• Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
• Participants with no prior treatment for Stage IV non-squamous NSCLC
• Known PD-L1 status as determined by immunohistochemistry assay performed on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening
• Measurable disease as defined by RECIST v1.1
• Adequate hematologic and end organ function

Exclusion criteria

Cancer-Specific Exclusions:

• Active or untreated central nervous system metastases
• Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome

General Medical Exclusions:

• Pregnant or lactating women
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Positive test for human immunodeficiency virus
• Active hepatitis B or hepatitis C
• Severe infection within 4 weeks prior to randomization
• Significant cardiovascular disease
• Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures

Exclusion Criteria Related to Medications:

• Prior treatment with cluster of differentiation 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1, and anti-PD-L1 therapeutic antibodies

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,202 participants in 3 patient groups

Arm A (Atezolizumab+Paclitaxel+Carboplatin)

Experimental group

Description:

Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

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

Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)

Experimental group

Description:

Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Drug: Bevacizumab

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

Arm C (Bevacizumab+Paclitaxel+Carboplatin)

Active Comparator group

Description:

Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Drug: Bevacizumab