A Phase II, Multicenter, Single-Arm Study OF Atezolizumab In Patients With PD-L1-Positive Locally Advanced Or Metastatic Non-Small Cell Lung Cancer

Hoffmann-La Roche110 sites in 5 countries667 target enrollmentJanuary 22, 2014

ConditionsNon-Small Cell Lung Cancer

InterventionsAtezolizumab

DrugsAtezolizumab

Overview

Phase: Phase 2
Intervention: Atezolizumab
Conditions: Non-Small Cell Lung Cancer
Sponsor: Hoffmann-La Roche
Enrollment: 667
Locations: 110
Primary Endpoint: Percentage of Participants Achieving Objective Response (ORR) Per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 as Assessed by Independent Review Facility (IRF)
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This multicenter, single-arm study will evaluate the efficacy and safety of Atezolizumab in participants with PD-L1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Participants will receive Atezolizumab 1200 milligrams (mg) intravenously every 3 weeks as long as participants are experiencing clinical benefit as assessed by the investigator, that is , in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.

Registry

clinicaltrials.gov

Start Date

January 22, 2014

End Date

January 11, 2019

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Adult participants greater than or equal to 18 years of age
•Locally advanced or metastatic (Stage IIIB, Stage IV, or recurrent) NSCLC
•Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens
•PD-L1-positive tumor status as determined by an immunohistochemistry (IHC) assay based on PD-L1 expression on tumor infiltrating immune cells and/or tumor cells performed by a central laboratory
•Measurable disease, as defined by RECIST version 1.1
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria

•Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment; the following exception are allowed:
•Hormone-replacement therapy or oral contraceptives tyrosine-kinase inhibitors (TKIs) approved for treatment of NSCLC discontinued \>7 days prior to Cycle 1, Day 1
•Central nervous system (CNS) disease, including treated brain metastases
•Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with negligible risk of metastases or death and treated with expected curative outcome
•History of autoimmune disease
•History of idiopathic pulmonary fibrosis (including pneumonia), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening CT scan. History of radiation pneumonitis in the radiation field (fibrosis) id permitted
•Active hepatitis B or hepatitis C
•Human Immunodeficiency virus (HIV) positive
•Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents

Arms & Interventions

Atezolizumab

Intervention: Atezolizumab

Outcomes

Primary Outcomes

Percentage of Participants Achieving Objective Response (ORR) Per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 as Assessed by Independent Review Facility (IRF)

Time Frame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)

ORR was the percentage of participants whose confirmed best overall response was either a Partial Response (PR) or a Complete Response (CR) based upon the IRF assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm); PR:greater than (\>) or equal to (=) 30 percent (%) decrease from baseline in sum of diameters of target lesions, non-progressive disease (PD) non-target lesions and no new lesions. Results were reported by line of therapy and programmed death-ligand 1 (PD-L1) Expression Subgroup (tumor cell \[TC\]3 \[TC3\] or tumor-infiltrating immune cell \[IC\] 3 \[IC3\], TC3 or IC2/3, TC2/3 or IC2/3).

Secondary Outcomes

Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
PFS: Percentage of Participants Alive and Progression Free at 6 Months(Month 6)
Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV)(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
DOR as Assessed by INV Per RECIST v1.1(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
DOR as Assessed by INV Per Modified RECIST(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
Percentage of Participants Without an Event (Death) at 6 Months(Month 6)
Percentage of Participants Without an Event (Death) at 12 Months(Month 12)
PFS as Assessed by INV Per RECIST v1.1(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
PFS as Assessed by INV Per Modified RECIST(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
Time in Response (TIR) as Assessed by INV Per RECIST v1.1(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
TIR as Assessed by INV Per Modified RECIST(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status(Baseline, post-baseline (up to 16 months))
Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
Duration of Response (DOR) Assessed by IRF Per RECIST v1.1(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
Overall Survival : Median Time to Event (Death)(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
Overall Survival : Percentage of Participants Without Event (Death)(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
Atezolizumab Serum Concentrations(Pre-dose (hour 0) and 0.5 hours post dose on Cycle 1 Day 1 (Cycle length = 21days), Cycle 1 Days 2, 4, 8, 15, and 21, Cycle 2 Day 21, Cycle 3 Day 21, Cycle 7 Day 21)
Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))
PFS: Percentage of Participants Alive and Progression Free at 12 Months(Month 12)
TIR as Assessed by IRF Per RECIST v1.1(Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months))