A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab Compared With Chemotherapy in Patients With Treatment Naïve Advanced or Recurrent (Stage IIIb Not Amenable for Multimodality Treatment) or Metastatic (Stage IV) Non-Small Cell Lung Cancer Who Are Deemed Unsuitable for Platinum-Containing Therapy

Hoffmann-La Roche91 sites in 11 countries453 target enrollmentSeptember 11, 2017

ConditionsNon-Small Cell Lung Cancer

InterventionsAtezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody Vinorelbine Gemcitabine

DrugsAtezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody Vinorelbine Gemcitabine

Overview

Phase: Phase 3
Intervention: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Conditions: Non-Small Cell Lung Cancer
Sponsor: Hoffmann-La Roche
Enrollment: 453
Locations: 91
Primary Endpoint: Overall Survival (OS)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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).

Registry

clinicaltrials.gov

Start Date

September 11, 2017

End Date

October 25, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

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:

Arms & Interventions

Atezolizumab

Participants will receive atezolizumab 1200 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death.

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

Single Agent Chemotherapy (Vinorelbine or Gemcitabine)

Participants will receive single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator's choice.

Intervention: Vinorelbine

Single Agent Chemotherapy (Vinorelbine or Gemcitabine)

Participants will receive single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator's choice.

Intervention: Gemcitabine

Outcomes

Primary Outcomes

Overall Survival (OS)

Time Frame: From randomization up to death from any cause (up to approximately 55 months)

OS was defined as the time between the date of randomization and the date of death due to any cause. Kaplan-Meier (KM) estimates were used to calculate median.

Secondary Outcomes

OS Rates at the 6, 12, 18, 24-Months Timepoints(6, 12, 18 and 24 months)
Percentage of Participants With Objective Response, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)(From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months))
Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1(From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months))
Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1(Time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first (up to approximately 55 months))
Percentage of Participants With At Least One Adverse Event (AE)(Baseline up to 90 days after last dose of atezolizumab (approximately 62 months))
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC-QLQ-C30) Score(Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days))
Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score(Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days))
Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score(From baseline up to approximately 55 months)
TTD in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score(From baseline up to approximately 55 months)
OS in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Status(From randomization up to death from any cause (up to approximately 55 months))
PFS as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status(From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months))