Phase 3
Completed N=453
A Study of Atezolizumab Compared With a Single-Agent Chemotherapy in Treatment Naïve Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy
Source: ClinicalTrials.gov NCT03191786 ↗Enrolled (actual)
453
Serious AEs
45.0%
Results posted
May 2023
Primary outcomePrimary: Overall Survival (OS) — 10.3; 9.2 Months — p=0.025
◆ Published Evidence
Highly cited
159citations · ~53 / year
First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study.
Summary
This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 [anti-PD-L1] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status of 2-3).
Linked Publications (5)
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First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study.
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Best first-line therapy for people with advanced non-small cell lung cancer, performance status 2 without a targetable mutation or with an unknown mutation status.
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Brief Report: Post Hoc Validation of Platinum Ineligibility in NSCLC From the Phase III IPSOS Study.
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First-line atezolizumab monotherapy vs. single-agent chemotherapy in patients with advanced or metastatic non-small cell lung cancer who are ineligible for platinum-based therapy: Analysis of the IPSOS Asian subpopulation.
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Atezolizumab monotherapy as first-line treatment for non-small cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a cost-effectiveness analysis in the USA.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) |
10.3; 9.2 | 0.025 sig |
| SECONDARY OS Rates at the 6, 12, 18, 24-Months Timepoints |
64.0; 57.5; 43.7; 38.6; 31.4; 24.0 | — |
| SECONDARY Percentage of Participants With Objective Response, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) |
16.9; 7.9 | — |
| SECONDARY Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1 |
4.2; 4.0 | 0.182 |
| SECONDARY Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1 |
14.0; 7.8 | — |
| SECONDARY Percentage of Participants With At Least One Adverse Event (AE) |
91.7; 97.3 | — |
| SECONDARY Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC-QLQ-C30) Score |
54.70; 55.25; 2.09; 0.29; 2.76; 1.85 | — |
| SECONDARY Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score |
34.30; 36.67; 1.13; 0.92; -0.23; -2.87 | — |
| SECONDARY Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score |
NA; NA; 13.5; 8.4 | 0.975 |
| SECONDARY TTD in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score |
NA; 21.4; NA; NA; 17.3; 8.3 | 0.653 |
| SECONDARY OS in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Status |
9.4; 10.3 | 0.272 |
| SECONDARY PFS as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status |
4.2; 3.0 | 0.366 |
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
Cancer-Specific Exclusion Criteria:
- 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
General Medical Exclusion Criteria:
- 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 unstabl
Data sourced from ClinicalTrials.gov (NCT03191786) and the linked publication. 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. Informational only — not medical advice.