Phase 3 N=723 Randomized Treatment

A Study of Atezolizumab in Combination With Carboplatin Plus (+) Nab-Paclitaxel Compared With Carboplatin+Nab-Paclitaxel in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Carcinoma, Non-Squamous Non-Small Cell Lung

Bottom Line

View on ClinicalTrials.gov: NCT02367781 ↗

Enrolled (actual)

723

Serious AEs

48.1%

Results posted

Apr 2019

Primary outcome: Primary: Progression-Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the ITT-WT Population — 7.0; 5.5 Months — p=<.0001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody (Drug); Carboplatin (Drug); Nab-Paclitaxel (Drug); Pemetrexed (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Hoffmann-La Roche
Primary completion: Mar 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Progression-Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the ITT-WT Population	7.0; 5.5	<.0001 sig
PRIMARY Overall Survival (OS) in the ITT-WT Population	18.6; 13.9	0.0298 sig
SECONDARY PFS as Determined by the Investigator Using Recist v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population	7.0; 5.6; 7.5; 5.7; 7.5; 5.9	<0.0001 sig
SECONDARY OS as Determined by the Investigator Using Recist v1.1 in the ITT Population	17.0; 13.5	0.0732
SECONDARY OS as Determined by the Investigator Using RECIST v1.1 in the PD-L1 Expression Population and PD-L1 Expression WT Population	21.2; 16.9; 21.2; 16.9	0.0830
SECONDARY Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using RECIST v1.1 in the ITT-WT Population	60.2; 41.0	<.0001 sig
SECONDARY Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using RECIST v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population	59.1; 42.2; 65.6; 46.2; 64.6; 45.0	<.0001 sig
SECONDARY Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 in ITT-WT Population, ITT Population, and PD-L1 Expression Population and PD-L1 Expression WT Population	6.2; 5.4; 6.7; 5.4; 7.2; 5.0	0.0002 sig
SECONDARY Event Free Rate (%) at Year 1 and 2 in ITT-WT Population and ITT Population	62.02; 54.56; 40.43; 32.36; 61.65; 54.47	0.0647
SECONDARY Event Free Rate (%) at Year 1 and 2 in PD-L1 Expression Population and PD-L1 Expression WT Population	68.56; 61.86; 44.63; 35.98; 68.84; 62.51	0.2385
SECONDARY Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms in the ITT-WT Population	2.2; 1.9	0.3342
SECONDARY Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale	0.19; 0.14; -0.02; 0.03; -0.05; 0.01	—
SECONDARY Percentage of Participants With Adverse Events	99.6; 98.7	—
SECONDARY Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab	3.1; 4.8; 22.4; 23.5	—
SECONDARY Maximum Observed Serum Concentration (Cmax) of Atezolizumab for Patients in Atezolizumab+Carboplatin+Nab-Paclitaxel Arm	392; 454	—
SECONDARY Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Atezolizumab+Carboplain+Nab-Paclitaxel	70.9; 111; 134; 218	—
SECONDARY Plasma Concentrations of Carboplatin	NA; NA; 20,500; 17,000; 11,900; 12,400	—
SECONDARY Plasma Concentrations of Nab-Paclitaxel Reported as Total Paclitaxel	NA; NA; 3520; 2530; 307; 417	—

Summary

This randomized Phase III, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab (an engineered anti-programmed death-ligand 1 [PD-L1] antibody) in combination with carboplatin+nab-paclitaxel compared with treatment with carboplatin+nab-paclitaxel in chemotherapy-naive participants with Stage IV non-squamous NSCLC. Participants were randomized in a 2:1 ratio to Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin) or Arm B (Nab-Paclitaxel+Carboplatin).

Eligibility Criteria

Inclusion Criteria

Eastern Cooperative Oncology Group performance status of 0 or 1
Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
Participants with no prior treatment for Stage IV non-squamous NSCLC
Previously obtained archival tumor tissue or tissue obtained from fresh 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02367781). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.