Phase 3
N=1,202
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)
Carcinoma, Non-Small-Cell Lung
Bottom Line
View on ClinicalTrials.gov: NCT02366143 ↗Enrolled (actual)
1,202
Serious AEs
42.3%
Results posted
Oct 2020
Primary outcome: Primary: Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population — 11.3; 6.8; 8.3; 6.8 Months — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody (Drug); Bevacizumab (Drug); Carboplatin (Drug); Paclitaxel (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Sep 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population |
11.3; 6.8; 8.3; 6.8 | <0.0001 sig |
| PRIMARY Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population |
19.2; 14.7 | 0.0164 sig |
| PRIMARY Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population |
19.0; 14.7 | 0.0528 |
| SECONDARY PFS, as Determined by the Independent Review Facility (IRF) in Arm B Versus Arm C in Teff-High-WT Population and ITT-WT Population |
10.7; 7.0; 8.5; 7.0 | 0.0002 sig |
| SECONDARY PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population |
11.3; 6.8; 8.3; 6.8 | <.0001 sig |
| SECONDARY PFS, as Determined by the Investigator in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population |
6.3; 11.3; 6.3; 8.3 | — |
| SECONDARY PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup |
11.1; 6.8; 11.0; 6.8 | <.0001 sig |
| SECONDARY OS in Arm B Versus Arm C by PD-L1 Subgroup |
22.2; 16.7; 22.5; 16.4 | 0.2765 |
| SECONDARY OS in Arm A Versus Arm C by PD-L1 Subgroup |
26.1; 17.0; 24.4; 16.0 | 0.0073 sig |
| SECONDARY OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population |
25.0; 16.7; 25.2; 16.7; 19.8; 14.9 | 0.2843 |
| SECONDARY OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population |
21.3; 16.3; 21.0; 16.7; 19.0; 15.0 | 0.0894 |
| SECONDARY OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population |
21.3; 25.8; 19.0; 19.5 | 0.4599 |
| SECONDARY Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C |
11.2; 5.7; 9.0; 5.7 | <.0001 sig |
| SECONDARY Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator in the Teff-High-WT Population and ITT-WT Population |
54.0; 69.3; 53.5; 49.3; 63.5; 48.0 | — |
| SECONDARY OS Rates at Years 1 and 2 in Arm B Versus Arm C |
68.63; 58.74; 67.32; 60.63; 52.03; 41.70 | 0.0697 |
| SECONDARY OS Rates at Years 1 and 2 in Arm A Versus Arm C |
67.48; 56.92; 46.01; 38.74; 64.06; 59.89 | 0.2624 |
| SECONDARY Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms Determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score |
NA; NA; NA; NA; NA; NA | 0.6899 |
| SECONDARY TTD in Patient-Reported Lung Cancer Symptoms as Determined by EORTC Quality-of-Life Questionnaire-Core Lung Cancer Module 13 (QLQ-LC13) Score |
NA; NA; NA; NA; NA; NA | 0.8816 |
| SECONDARY Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale |
— | — |
| SECONDARY Percentage of Participants With Adverse Events |
99.0; 98.2; 97.8 | — |
| SECONDARY Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab |
4.6; 2.9 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B |
410; 414; 498; 540 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B |
76.4; 80.8; 119; 130; 146; 160 | — |
| SECONDARY Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C |
NA; NA; NA; 18300; 18300; 17200 | — |
| SECONDARY Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C |
NA; NA; NA; 4850; 6440; 5560 | — |
| SECONDARY Cmax of Bevacizumab in Arm B and Arm C |
329; 323; 413; 430 | — |
| SECONDARY Cmin of Bevacizumab in Arm B and Arm C |
NA; NA; 98.0; 90.4 | — |
Summary
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).
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02366143). 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.