Description:
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.
Title
- Brief Title: A Study of Atezolizumab in Participants With Programmed Death - Ligand 1 (PD-L1) Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer
- Official Title: A Phase II, Multicenter, Single-Arm Study OF Atezolizumab In Patients With PD-L1-Positive Locally Advanced Or Metastatic Non-Small Cell Lung Cancer
Clinical Trial IDs
- ORG STUDY ID:
GO28754
- SECONDARY ID:
2013-003330-32
- NCT ID:
NCT02031458
Conditions
- Non-Small Cell Lung Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Atezolizumab | | Atezolizumab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Atezolizumab | Experimental | | |
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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 Outcome Measures
| Measure: | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) |
| 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) |
| Safety Issue: | |
| Description: | ORR was the percentage of participants whose confirmed best overall response was either a PR or a CR based upon the Investigator 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 <10mm; PR: > or = 30 % decrease from baseline in sum of diameters of target lesions, non-PD non-target lesions and no new lesions. Results were reported by line of therapy (reporting arms) and PD-L1 Expression Subgroup (TC3 or IC3, TC3 or IC2/3, TC2/3 or IC2/3). |
| Measure: | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV |
| 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) |
| Safety Issue: | |
| Description: | ORR was the percentage of participants whose confirmed best overall response was either a PR or a CR based upon the Investigator assessment per modified RECIST. CR: disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10mm; PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR. Results were reported by line of therapy (reporting arms) and PD-L1 Expression Subgroup (TC3 or IC3, TC3 or IC2/3, TC2/3 or IC2/3). |
| Measure: | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 |
| 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) |
| Safety Issue: | |
| Description: | DOR is interval between date of first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and the first date that PD or death is documented, whichever occurs first as measured by 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 <10mm; PR: > or = 30 % decrease from baseline in sum of diameters of target lesions, non-PD non-target lesions and no new lesions; PD: one or more of the following: at least 20% increase from nadir in sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. DOR was assessed by Kaplan-Meier estimates. Results were reported by line of therapy (reporting arms) and PD-L1 Expression Subgroup (TC3 or IC3, TC3 or IC2/3, TC2/3 or IC2/3). |
| Measure: | DOR as Assessed by INV Per RECIST v1.1 |
| 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) |
| Safety Issue: | |
| Description: | DOR is interval between date of the first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and first date that PD or death is documented, whichever occurs first as measured by 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 <10mm; PR: > or = 30 % decrease from baseline in sum of diameters of target lesions, non-PD non-target lesions and no new lesions; PD: one or more of the following: at least 20% increase from nadir in sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. DOR was assessed by Kaplan-Meier estimates. Results were reported by line of therapy (reporting arms) and PD-L1 Expression Subgroup (TC3 or IC3, TC3 or IC2/3, TC2/3 or IC2/3). |
| Measure: | DOR as Assessed by INV Per Modified RECIST |
| 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) |
| Safety Issue: | |
| Description: | DOR is the interval between the date of the first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and the first date that PD or death is documented, whichever occurs first as measured by modified RECIST. CR: disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10mm; PR: at least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR; PD: one or more of the following: at least 20% increase from nadir in the sum of diameters of existing and/or new target lesions (with an absolute increase of at least 5mm). DOR was assessed by Kaplan-Meier estimates. Results were reported by line of therapy (reporting arms) and PD-L1 Expression Subgroup (TC3 or IC3, TC3 or IC2/3, TC2/3 or IC2/3). |
| Measure: | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 |
| 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) |
| Safety Issue: | |
| Description: | PFS is the interval between the first dose of atezolizumab and date of disease progression or death due to any cause, whichever occurred first as measured by RECIST v1.1. PD is defined as one or more of the following: at least 20% increase from nadir in the sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. PFS was assessed by Kaplan-Meier estimates. |
| Measure: | PFS as Assessed by INV Per RECIST v1.1 |
| 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) |
| Safety Issue: | |
| Description: | PFS is the interval between the first dose of atezolizumab and date of disease progression or death due to any cause, whichever occurred first as measured by RECIST v1.1. PD: one or more of the following: at least 20% increase from nadir in the sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. PFS was assessed by Kaplan-Meier estimates. |
| Measure: | PFS as Assessed by INV Per Modified RECIST |
| 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) |
| Safety Issue: | |
| Description: | PFS is the interval between the first dose of atezolizumab and date of disease progression or death due to any cause, whichever occurred first as measured by modified RECIST. PD: at least 20% increase from nadir in the sum of diameters of new and/or existing target lesions (with an absolute increase of at least 5mm). PFS was assessed by Kaplan-Meier estimates. |
| Measure: | Overall Survival : Percentage of Participants Without Event (Death) |
| 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Overall Survival : Median Time to Event (Death) |
| 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) |
| Safety Issue: | |
| Description: | Overall survival is measured as interval between the first dose of atezolizumab and date of death from any cause. |
| Measure: | Percentage of Participants Without an Event (Death) at 6 Months |
| Time Frame: | Month 6 |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants Without an Event (Death) at 12 Months |
| Time Frame: | Month 12 |
| Safety Issue: | |
| Description: | |
| Measure: | PFS: Percentage of Participants Alive and Progression Free at 6 Months |
| Time Frame: | Month 6 |
| Safety Issue: | |
| Description: | PD is defined as one or more of the following: at least 20% increase from nadir in the sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. |
| Measure: | PFS: Percentage of Participants Alive and Progression Free at 12 Months |
| Time Frame: | Month 12 |
| Safety Issue: | |
| Description: | PD is defined as one or more of the following: at least 20% increase from nadir in the sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. |
| Measure: | Time in Response (TIR) as Assessed by INV Per RECIST v1.1 |
| 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) |
| Safety Issue: | |
| Description: | TIR is interval between date of first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and first date that PD or death is documented, whichever occurs first as measured by RECIST v1.1. For responders, TIR was the same as DOR; for non-responders, TIR was considered as an event and defined as the date of first treatment plus one day. TIR was assessed by Kaplan-Meier estimates. |
| Measure: | TIR as Assessed by INV Per Modified RECIST |
| 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) |
| Safety Issue: | |
| Description: | TIR is interval between date of first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and first date that PD or death is documented, whichever occurs first as measured by modified RECIST. For responders, TIR was the same as DOR; for non-responders, TIR was considered as an event and defined as the date of first treatment plus one day. TIR was assessed by Kaplan-Meier estimates. |
| Measure: | TIR as Assessed by IRF Per RECIST v1.1 |
| 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) |
| Safety Issue: | |
| Description: | TIR is interval between date of first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and first date that PD or death is documented, whichever occurs first as measured by RECIST v1.1. For responders, TIR was the same as DOR; for non-responders, TIR was considered as an event and defined as the date of first treatment plus one day. TIR was assessed by Kaplan-Meier estimates. |
| Measure: | Atezolizumab Serum Concentrations |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Serum concentrations were determined for all participants after administration of atezolizumab up to Cycle 8. Time (T) = time from first dose in days. |
| Measure: | Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status |
| Time Frame: | Baseline, post-baseline (up to 16 months) |
| Safety Issue: | |
| Description: | Anti-therapeutic antibodies is a measurement to explore the potential relationship of immunogenicity response with pharmacokinetics, safety and efficacy. |
| Measure: | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 |
| 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) |
| Safety Issue: | |
| Description: | PD was defined as one or more of the following: at least 20% increase from nadir in the sum of diameters of target lesions (with an absolute increase of at least 5 mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. |
| Measure: | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 |
| 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) |
| Safety Issue: | |
| Description: | PD was defined as one or more of the following: at least 20% increase from nadir in the sum of diameters of target lesions (with an absolute increase of at least 5 mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. |
| Measure: | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 |
| 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) |
| Safety Issue: | |
| Description: | PD was defined as at least 20% increase from nadir in the sum of diameters of new and/or existing target lesions (with an absolute increase of at least 5 mm). |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Hoffmann-La Roche |
Last Updated
January 6, 2020
