Non-Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGAtezolizumab
1200 mg IV every 3 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 is measured as interval between the first dose of atezolizumab and date of death from any cause. |
| Percentage of Participants Without an Event (Death) at 6 Months | Month 6 | — |
| 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) | 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). |
| 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) | 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). |
| 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) | 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). |
| 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 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). |
| Percentage of Participants Without an Event (Death) at 12 Months | Month 12 | — |
| PFS: Percentage of Participants Alive and Progression Free at 6 Months | Month 6 | 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. |
| 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) | 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). |
| 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 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. |
| PFS: Percentage of Participants Alive and Progression Free at 12 Months | Month 12 | 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 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) | 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. |
| 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) | — |
| 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 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. |
| 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) | 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. |
| 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) | 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. |
| 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 | Serum concentrations were determined for all participants after administration of atezolizumab up to Cycle 8. Time (T) = time from first dose in days. |
| Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status | Baseline, post-baseline (up to 16 months) | Anti-therapeutic antibodies is a measurement to explore the potential relationship of immunogenicity response with pharmacokinetics, safety and efficacy. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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). |
| 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 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. |
Countries
Australia, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, France, Georgia, Germany, Hong Kong, Italy, Japan, Netherlands, Singapore, Slovenia, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Since the primary cut-off date May 8, 2015 one participant in Cohort 1 has moved to Cohort 2 and one participant in Cohort 3 was moved to Cohort 2.
Pre-assignment details
Screening was performed from Day -28 to Day -1.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: First Line Atezolizumab Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting. | 138 |
| Cohort 2: Second Line Atezolizumab Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting. | 269 |
| Cohort 3: Third Line and Beyond Atezolizumab Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting. | 252 |
| Total | 659 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Baseline to May 8, 2015 | Death | 36 | 87 | 100 |
| Baseline to May 8, 2015 | Lost to Follow-up | 1 | 1 | 2 |
| Baseline to May 8, 2015 | On Survival Follow-Up | 46 | 83 | 73 |
| Baseline to May 8, 2015 | On Treatment | 43 | 81 | 73 |
| Baseline to May 8, 2015 | Physician Decision | 0 | 1 | 0 |
| Baseline to May 8, 2015 | Protocol Violation | 7 | 4 | 0 |
| Baseline to May 8, 2015 | Unknown Reason | 0 | 1 | 2 |
| Baseline to May 8, 2015 | Withdrawal by Subject | 6 | 9 | 3 |
| May 8, 2015 to January 11, 2019 | Death | 89 | 193 | 198 |
| May 8, 2015 to January 11, 2019 | Lost to Follow-up | 2 | 5 | 8 |
| May 8, 2015 to January 11, 2019 | Physician Decision | 2 | 3 | 3 |
| May 8, 2015 to January 11, 2019 | Protocol Violation | 7 | 4 | 0 |
| May 8, 2015 to January 11, 2019 | Study Terminated by Sponsor | 24 | 42 | 23 |
| May 8, 2015 to January 11, 2019 | Switched over to commercial Atezolizumab | 1 | 6 | 6 |
| May 8, 2015 to January 11, 2019 | Withdrawal by Subject | 13 | 16 | 14 |
Baseline characteristics
| Characteristic | Cohort 1: First Line Atezolizumab | Cohort 2: Second Line Atezolizumab | Cohort 3: Third Line and Beyond Atezolizumab | Total |
|---|---|---|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 10.3 | 62.4 years STANDARD_DEVIATION 10.2 | 63.6 years STANDARD_DEVIATION 9.4 | 63.7 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 68 Participants | 104 Participants | 100 Participants | 272 Participants |
| Sex: Female, Male Male | 70 Participants | 165 Participants | 152 Participants | 387 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 89 / 138 | 193 / 269 | 198 / 252 |
| other Total, other adverse events | 116 / 138 | 229 / 269 | 229 / 252 |
| serious Total, serious adverse events | 47 / 138 | 117 / 269 | 113 / 252 |
Outcome results
Primary
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)
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).
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)
Population: Efficacy evaluable population; Number (n) equals (=) number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | 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) | TC2/3 or IC2/3 Responders | 19.4 percentage of participants |
| Cohort 1: First Line Atezolizumab | 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) | TC3 or IC2/3 Responders | 21.1 percentage of participants |
| Cohort 1: First Line Atezolizumab | 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) | TC3 or IC3 Responders | 26.2 percentage of participants |
| Cohort 2: Second Line Atezolizumab | 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) | TC3 or IC2/3 Responders | 17.4 percentage of participants |
| Cohort 2: Second Line Atezolizumab | 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) | TC3 or IC3 Responders | 23.8 percentage of participants |
| Cohort 2: Second Line Atezolizumab | 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) | TC2/3 or IC2/3 Responders | 17.2 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | 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) | TC3 or IC3 Responders | 27.0 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | 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) | TC3 or IC2/3 Responders | 18.2 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | 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) | TC2/3 or IC2/3 Responders | 17.4 percentage of participants |
| Cohorts 2 + 3 | 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) | TC3 or IC2/3 Responders | 17.8 percentage of participants |
| Cohorts 2 + 3 | 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) | TC2/3 or IC2/3 Responders | 17.3 percentage of participants |
| Cohorts 2 + 3 | 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) | TC3 or IC3 Responders | 25.35 percentage of participants |
Secondary
Atezolizumab Serum Concentrations
Serum concentrations were determined for all participants after administration of atezolizumab up to Cycle 8. Time (T) = time from first dose in days.
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
Population: Pharmacokinetic evaluable population; n = number of participants analyzed for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Atezolizumab Serum Concentrations | Cycle 1 Day 1 T=0 | 0.285 micrograms per milliliter (μg/mL) | Standard Deviation 4.35 |
| Cohort 1: First Line Atezolizumab | Atezolizumab Serum Concentrations | Cycle 1 Day 1 T=0.021 | 429.0 micrograms per milliliter (μg/mL) | Standard Deviation 218 |
| Cohort 1: First Line Atezolizumab | Atezolizumab Serum Concentrations | Cycle 1 Day 2 T=1 | 299.0 micrograms per milliliter (μg/mL) | Standard Deviation 65.3 |
| Cohort 1: First Line Atezolizumab | Atezolizumab Serum Concentrations | Cycle 1 Day 4 T=3 | 220.0 micrograms per milliliter (μg/mL) | Standard Deviation 48.4 |
| Cohort 1: First Line Atezolizumab | Atezolizumab Serum Concentrations | Cycle 1 Day 8 T=7 | 155.0 micrograms per milliliter (μg/mL) | Standard Deviation 35.4 |
| Cohort 1: First Line Atezolizumab | Atezolizumab Serum Concentrations | Cycle 1 Day 15 T=14 | 106.0 micrograms per milliliter (μg/mL) | Standard Deviation 32.1 |
| Cohort 1: First Line Atezolizumab | Atezolizumab Serum Concentrations | Cycle 1 Day 21 T=21 | 87.8 micrograms per milliliter (μg/mL) | Standard Deviation 41.7 |
| Cohort 1: First Line Atezolizumab | Atezolizumab Serum Concentrations | Cycle 2 Day 21 T=42 | 134.0 micrograms per milliliter (μg/mL) | Standard Deviation 57.2 |
| Cohort 1: First Line Atezolizumab | Atezolizumab Serum Concentrations | Cycle 3 Day 21 T=63 | 163.0 micrograms per milliliter (μg/mL) | Standard Deviation 70.7 |
| Cohort 1: First Line Atezolizumab | Atezolizumab Serum Concentrations | Cycle 7 Day 21 T=147 | 212.0 micrograms per milliliter (μg/mL) | Standard Deviation 88.5 |
Secondary
DOR as Assessed by INV Per Modified RECIST
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).
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)
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group. Number of participants analyzed = overall number of participants who were evaluable for this outcome
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | DOR as Assessed by INV Per Modified RECIST | TC3 or IC3 DOR | NA months |
| Cohort 1: First Line Atezolizumab | DOR as Assessed by INV Per Modified RECIST | TC3 or IC2/3 DOR | NA months |
| Cohort 1: First Line Atezolizumab | DOR as Assessed by INV Per Modified RECIST | TC2/3 or IC2/3 DOR | NA months |
| Cohort 2: Second Line Atezolizumab | DOR as Assessed by INV Per Modified RECIST | TC3 or IC3 DOR | NA months |
| Cohort 2: Second Line Atezolizumab | DOR as Assessed by INV Per Modified RECIST | TC2/3 or IC2/3 DOR | NA months |
| Cohort 2: Second Line Atezolizumab | DOR as Assessed by INV Per Modified RECIST | TC3 or IC2/3 DOR | NA months |
| Cohort 3: Third Line and Beyond Atezolizumab | DOR as Assessed by INV Per Modified RECIST | TC2/3 or IC2/3 DOR | NA months |
| Cohort 3: Third Line and Beyond Atezolizumab | DOR as Assessed by INV Per Modified RECIST | TC3 or IC3 DOR | NA months |
| Cohort 3: Third Line and Beyond Atezolizumab | DOR as Assessed by INV Per Modified RECIST | TC3 or IC2/3 DOR | NA months |
| Cohorts 2 + 3 | DOR as Assessed by INV Per Modified RECIST | TC3 or IC3 DOR | NA months |
| Cohorts 2 + 3 | DOR as Assessed by INV Per Modified RECIST | TC2/3 or IC2/3 DOR | NA months |
| Cohorts 2 + 3 | DOR as Assessed by INV Per Modified RECIST | TC3 or IC2/3 DOR | NA months |
Secondary
DOR as Assessed by INV Per RECIST v1.1
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).
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)
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group. Number of participants analyzed = overall number of participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | DOR as Assessed by INV Per RECIST v1.1 | TC3 or IC3 DOR | 8.5 months |
| Cohort 1: First Line Atezolizumab | DOR as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 DOR | 8.5 months |
| Cohort 1: First Line Atezolizumab | DOR as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 DOR | NA months |
| Cohort 2: Second Line Atezolizumab | DOR as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 DOR | NA months |
| Cohort 2: Second Line Atezolizumab | DOR as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 DOR | NA months |
| Cohort 2: Second Line Atezolizumab | DOR as Assessed by INV Per RECIST v1.1 | TC3 or IC3 DOR | NA months |
| Cohort 3: Third Line and Beyond Atezolizumab | DOR as Assessed by INV Per RECIST v1.1 | TC3 or IC3 DOR | 8.4 months |
| Cohort 3: Third Line and Beyond Atezolizumab | DOR as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 DOR | 8.3 months |
| Cohort 3: Third Line and Beyond Atezolizumab | DOR as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 DOR | 8.3 months |
| Cohorts 2 + 3 | DOR as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 DOR | NA months |
| Cohorts 2 + 3 | DOR as Assessed by INV Per RECIST v1.1 | TC3 or IC3 DOR | NA months |
| Cohorts 2 + 3 | DOR as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 DOR | NA months |
Secondary
Duration of Response (DOR) Assessed by IRF Per RECIST v1.1
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).
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)
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group. Number of participants analyzed = overall number of participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 DOR | 8.5 months |
| Cohort 1: First Line Atezolizumab | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC3 or IC3 DOR | NA months |
| Cohort 1: First Line Atezolizumab | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 DOR | 8.5 months |
| Cohort 2: Second Line Atezolizumab | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 DOR | 8.4 months |
| Cohort 2: Second Line Atezolizumab | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC3 or IC3 DOR | NA months |
| Cohort 2: Second Line Atezolizumab | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 DOR | 8.4 months |
| Cohort 3: Third Line and Beyond Atezolizumab | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 DOR | 8.4 months |
| Cohort 3: Third Line and Beyond Atezolizumab | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC3 or IC3 DOR | 7.2 months |
| Cohort 3: Third Line and Beyond Atezolizumab | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 DOR | 8.4 months |
| Cohorts 2 + 3 | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC3 or IC3 DOR | 7.2 months |
| Cohorts 2 + 3 | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 DOR | 8.4 months |
| Cohorts 2 + 3 | Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 DOR | 8.4 months |
Secondary
Overall Survival : Median Time to Event (Death)
Overall survival is measured as interval between the first dose of atezolizumab and date of death from any cause.
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)
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Overall Survival : Median Time to Event (Death) | TC3 or IC3 | NA months |
| Cohort 1: First Line Atezolizumab | Overall Survival : Median Time to Event (Death) | TC2/3 or IC2/3 | 14.0 months |
| Cohort 1: First Line Atezolizumab | Overall Survival : Median Time to Event (Death) | TC3 or IC2/3 | 14.0 months |
| Cohort 2: Second Line Atezolizumab | Overall Survival : Median Time to Event (Death) | TC3 or IC3 | NA months |
| Cohort 2: Second Line Atezolizumab | Overall Survival : Median Time to Event (Death) | TC3 or IC2/3 | NA months |
| Cohort 2: Second Line Atezolizumab | Overall Survival : Median Time to Event (Death) | TC2/3 or IC2/3 | NA months |
| Cohort 3: Third Line and Beyond Atezolizumab | Overall Survival : Median Time to Event (Death) | TC3 or IC2/3 | NA months |
| Cohort 3: Third Line and Beyond Atezolizumab | Overall Survival : Median Time to Event (Death) | TC3 or IC3 | NA months |
| Cohort 3: Third Line and Beyond Atezolizumab | Overall Survival : Median Time to Event (Death) | TC2/3 or IC2/3 | NA months |
| Cohorts 2 + 3 | Overall Survival : Median Time to Event (Death) | TC2/3 or IC2/3 | NA months |
| Cohorts 2 + 3 | Overall Survival : Median Time to Event (Death) | TC3 or IC2/3 | NA months |
| Cohorts 2 + 3 | Overall Survival : Median Time to Event (Death) | TC3 or IC3 | NA months |
Secondary
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)
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Overall Survival : Percentage of Participants Without Event (Death) | TC3 or IC3 | 70.8 percentage of participants |
| Cohort 1: First Line Atezolizumab | Overall Survival : Percentage of Participants Without Event (Death) | TC2/3 or IC2/3 | 74.1 percentage of participants |
| Cohort 1: First Line Atezolizumab | Overall Survival : Percentage of Participants Without Event (Death) | TC3 or IC2/3 | 75.6 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Overall Survival : Percentage of Participants Without Event (Death) | TC3 or IC3 | 70.5 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Overall Survival : Percentage of Participants Without Event (Death) | TC2/3 or IC2/3 | 67.4 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Overall Survival : Percentage of Participants Without Event (Death) | TC3 or IC2/3 | 69.2 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Overall Survival : Percentage of Participants Without Event (Death) | TC3 or IC2/3 | 60.6 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Overall Survival : Percentage of Participants Without Event (Death) | TC3 or IC3 | 67.0 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Overall Survival : Percentage of Participants Without Event (Death) | TC2/3 or IC2/3 | 60.5 percentage of participants |
| Cohorts 2 + 3 | Overall Survival : Percentage of Participants Without Event (Death) | TC3 or IC3 | 68.8 percentage of participants |
| Cohorts 2 + 3 | Overall Survival : Percentage of Participants Without Event (Death) | TC2/3 or IC2/3 | 64.0 percentage of participants |
| Cohorts 2 + 3 | Overall Survival : Percentage of Participants Without Event (Death) | TC3 or IC2/3 | 65.0 percentage of participants |
Secondary
Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV
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).
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)
Population: Efficacy evaluable population; n= number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC2/3 or IC2/3 Responders | 15.8 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC3 or IC3 Responders | 20.0 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC3 or IC2/3 Responders | 16.3 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC3 or IC2/3 Responders | 21.9 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC2/3 or IC2/3 Responders | 21.0 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC3 or IC3 Responders | 27.0 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC3 or IC3 Responders | 30.4 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC2/3 or IC2/3 Responders | 19.8 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC3 or IC2/3 Responders | 20.8 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC2/3 or IC2/3 Responders | 20.4 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC3 or IC3 Responders | 28.7 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV | TC3 or IC2/3 Responders | 21.3 percentage of participants |
Secondary
Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV)
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).
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)
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC3 or IC3 Responders | 30.8 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC2/3 or IC2/3 Responders (n= 139, 267, 253, 520) | 22.3 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC3 or IC2/3 Responders | 24.4 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC3 or IC3 Responders | 24.6 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC2/3 or IC2/3 Responders (n= 139, 267, 253, 520) | 18.7 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC3 or IC2/3 Responders | 19.4 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC3 or IC2/3 Responders | 19.1 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC3 or IC3 Responders | 28.7 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC2/3 or IC2/3 Responders (n= 139, 267, 253, 520) | 18.2 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC3 or IC3 Responders | 26.6 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC2/3 or IC2/3 Responders (n= 139, 267, 253, 520) | 18.5 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) | TC3 or IC2/3 Responders | 19.3 percentage of participants |
Secondary
Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1
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).
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)
Population: Efficacy evaluable population; n = number of participants analyzed at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC2/3 or IC2/3 | 39.6 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC3 or IC2/3 | 38.2 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC3 or IC3 | 36.9 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC2/3 or IC2/3 | 62.9 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC3 or IC3 | 56.6 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC3 or IC2/3 | 61.5 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC3 or IC3 | 60.0 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC2/3 or IC2/3 | 66.4 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC3 or IC2/3 | 66.1 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC3 or IC2/3 | 63.8 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC2/3 or IC2/3 | 64.6 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 | TC3 or IC3 | 58.2 percentage of participants |
Secondary
Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1
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.
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)
Population: Efficacy evaluable population; n = number of participants analyzed at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC3 or IC3 | 50.8 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 | 52.5 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 | 50.4 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC3 or IC3 | 63.1 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 | 70.0 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 | 68.8 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 | 74.6 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC3 or IC3 | 68.7 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 | 74.7 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC3 or IC3 | 65.8 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 | 72.3 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 | 71.6 percentage of participants |
Secondary
Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1
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.
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)
Population: Efficacy evaluable population; n = number of participants analyzed at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC3 or IC3 | 58.5 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 | 63.3 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 | 61.8 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC3 or IC3 | 68.0 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 | 73.7 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 | 75.3 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 | 79.2 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC3 or IC3 | 73.0 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 | 79.1 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 | 77.1 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 | 76.4 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 | TC3 or IC3 | 70.5 percentage of participants |
Secondary
Percentage of Participants Without an Event (Death) at 12 Months
Time frame: Month 12
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Percentage of Participants Without an Event (Death) at 12 Months | TC3 or IC3 | 58.6 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants Without an Event (Death) at 12 Months | TC2/3 or IC2/3 | 65.0 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants Without an Event (Death) at 12 Months | TC3 or IC2/3 | 67.1 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Without an Event (Death) at 12 Months | TC3 or IC3 | 61.5 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Without an Event (Death) at 12 Months | TC2/3 or IC2/3 | 57.2 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Without an Event (Death) at 12 Months | TC3 or IC2/3 | 59.3 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Without an Event (Death) at 12 Months | TC3 or IC2/3 | 54.9 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Without an Event (Death) at 12 Months | TC3 or IC3 | 62.6 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Without an Event (Death) at 12 Months | TC2/3 or IC2/3 | 54.4 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Without an Event (Death) at 12 Months | TC3 or IC3 | 61.3 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Without an Event (Death) at 12 Months | TC2/3 or IC2/3 | 55.3 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Without an Event (Death) at 12 Months | TC3 or IC2/3 | 56.5 percentage of participants |
Secondary
Percentage of Participants Without an Event (Death) at 6 Months
Time frame: Month 6
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Percentage of Participants Without an Event (Death) at 6 Months | TC3 or IC3 | 79.2 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants Without an Event (Death) at 6 Months | TC2/3 or IC2/3 | 81.7 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants Without an Event (Death) at 6 Months | TC3 or IC2/3 | 83.9 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Without an Event (Death) at 6 Months | TC3 or IC3 | 79.7 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Without an Event (Death) at 6 Months | TC2/3 or IC2/3 | 76.2 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants Without an Event (Death) at 6 Months | TC3 or IC2/3 | 78.1 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Without an Event (Death) at 6 Months | TC3 or IC2/3 | 71.0 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Without an Event (Death) at 6 Months | TC3 or IC3 | 75.1 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants Without an Event (Death) at 6 Months | TC2/3 or IC2/3 | 70.5 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Without an Event (Death) at 6 Months | TC3 or IC3 | 77.4 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Without an Event (Death) at 6 Months | TC2/3 or IC2/3 | 73.4 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants Without an Event (Death) at 6 Months | TC3 or IC2/3 | 74.6 percentage of participants |
Secondary
Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status
Anti-therapeutic antibodies is a measurement to explore the potential relationship of immunogenicity response with pharmacokinetics, safety and efficacy.
Time frame: Baseline, post-baseline (up to 16 months)
Population: Efficacy evaluable population; n = number of participants analyzed at the specified time point. Number of participants analyzed = number participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status | Baseline | 7.4 percentage of participants |
| Cohort 1: First Line Atezolizumab | Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status | Post-Baseline | 45.1 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status | Post-Baseline | 36.0 percentage of participants |
| Cohort 2: Second Line Atezolizumab | Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status | Baseline | 3.5 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status | Baseline | 6.1 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status | Post-Baseline | 37.4 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status | Baseline | 4.8 percentage of participants |
| Cohorts 2 + 3 | Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status | Post-Baseline | 36.7 percentage of participants |
Secondary
PFS as Assessed by INV Per Modified RECIST
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.
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)
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | PFS as Assessed by INV Per Modified RECIST | TC3 or IC3 PFS | 7.1 months |
| Cohort 1: First Line Atezolizumab | PFS as Assessed by INV Per Modified RECIST | TC2/3 or IC2/3 PFS | 7.6 months |
| Cohort 1: First Line Atezolizumab | PFS as Assessed by INV Per Modified RECIST | TC3 or IC2/3 PFS | 7.9 months |
| Cohort 2: Second Line Atezolizumab | PFS as Assessed by INV Per Modified RECIST | TC2/3 or IC2/3 PFS | 4.2 months |
| Cohort 2: Second Line Atezolizumab | PFS as Assessed by INV Per Modified RECIST | TC3 or IC2/3 PFS | 4.5 months |
| Cohort 2: Second Line Atezolizumab | PFS as Assessed by INV Per Modified RECIST | TC3 or IC3 PFS | 5.7 months |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS as Assessed by INV Per Modified RECIST | TC3 or IC2/3 PFS | 4.9 months |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS as Assessed by INV Per Modified RECIST | TC3 or IC3 PFS | 6.3 months |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS as Assessed by INV Per Modified RECIST | TC2/3 or IC2/3 PFS | 4.6 months |
| Cohorts 2 + 3 | PFS as Assessed by INV Per Modified RECIST | TC2/3 or IC2/3 PFS | 4.4 months |
| Cohorts 2 + 3 | PFS as Assessed by INV Per Modified RECIST | TC3 or IC2/3 PFS | 4.6 months |
| Cohorts 2 + 3 | PFS as Assessed by INV Per Modified RECIST | TC3 or IC3 PFS | 5.8 months |
Secondary
PFS as Assessed by INV Per RECIST v1.1
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.
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)
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | PFS as Assessed by INV Per RECIST v1.1 | TC3 or IC3 PFS | 7.1 months |
| Cohort 1: First Line Atezolizumab | PFS as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 PFS | 7.1 months |
| Cohort 1: First Line Atezolizumab | PFS as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 PFS | 7.6 months |
| Cohort 2: Second Line Atezolizumab | PFS as Assessed by INV Per RECIST v1.1 | TC3 or IC3 PFS | 4.1 months |
| Cohort 2: Second Line Atezolizumab | PFS as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 PFS | 3.0 months |
| Cohort 2: Second Line Atezolizumab | PFS as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 PFS | 2.8 months |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 PFS | 3.5 months |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS as Assessed by INV Per RECIST v1.1 | TC3 or IC3 PFS | 4.2 months |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 PFS | 3.0 months |
| Cohorts 2 + 3 | PFS as Assessed by INV Per RECIST v1.1 | TC2/3 or IC2/3 PFS | 3.0 months |
| Cohorts 2 + 3 | PFS as Assessed by INV Per RECIST v1.1 | TC3 or IC2/3 PFS | 3.2 months |
| Cohorts 2 + 3 | PFS as Assessed by INV Per RECIST v1.1 | TC3 or IC3 PFS | 4.2 months |
Secondary
PFS: Percentage of Participants Alive and Progression Free at 12 Months
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.
Time frame: Month 12
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC2/3 or IC2/3 | 26.9 percentage of participants |
| Cohort 1: First Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC3 or IC3 | 33.1 percentage of participants |
| Cohort 1: First Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC3 or IC2/3 | 29.0 percentage of participants |
| Cohort 2: Second Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC3 or IC2/3 | 22.7 percentage of participants |
| Cohort 2: Second Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC3 or IC3 | 27.8 percentage of participants |
| Cohort 2: Second Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC2/3 or IC2/3 | 21.8 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC2/3 or IC2/3 | 14.7 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC3 or IC3 | 16.1 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC3 or IC2/3 | 15.1 percentage of participants |
| Cohorts 2 + 3 | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC3 or IC2/3 | 19.1 percentage of participants |
| Cohorts 2 + 3 | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC3 or IC3 | 23.1 percentage of participants |
| Cohorts 2 + 3 | PFS: Percentage of Participants Alive and Progression Free at 12 Months | TC2/3 or IC2/3 | 18.5 percentage of participants |
Secondary
PFS: Percentage of Participants Alive and Progression Free at 6 Months
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.
Time frame: Month 6
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC2/3 or IC2/3 | 56.4 percentage of participants |
| Cohort 1: First Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC3 or IC2/3 | 58.6 percentage of participants |
| Cohort 1: First Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC3 or IC3 | 57.4 percentage of participants |
| Cohort 2: Second Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC2/3 or IC2/3 | 34.8 percentage of participants |
| Cohort 2: Second Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC3 or IC3 | 41.3 percentage of participants |
| Cohort 2: Second Line Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC3 or IC2/3 | 36.1 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC3 or IC3 | 42.1 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC2/3 or IC2/3 | 34.7 percentage of participants |
| Cohort 3: Third Line and Beyond Atezolizumab | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC3 or IC2/3 | 35.8 percentage of participants |
| Cohorts 2 + 3 | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC3 or IC2/3 | 35.9 percentage of participants |
| Cohorts 2 + 3 | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC2/3 or IC2/3 | 34.8 percentage of participants |
| Cohorts 2 + 3 | PFS: Percentage of Participants Alive and Progression Free at 6 Months | TC3 or IC3 | 41.8 percentage of participants |
Secondary
Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1
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.
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)
Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: First Line Atezolizumab | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 PFS | 5.6 months |
| Cohort 1: First Line Atezolizumab | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 PFS | 5.5 months |
| Cohort 1: First Line Atezolizumab | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC3 or IC3 PFS | 5.5 months |
| Cohort 2: Second Line Atezolizumab | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC3 or IC3 PFS | 4.1 months |
| Cohort 2: Second Line Atezolizumab | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 PFS | 2.8 months |
| Cohort 2: Second Line Atezolizumab | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 PFS | 2.8 months |
| Cohort 3: Third Line and Beyond Atezolizumab | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 PFS | 2.8 months |
| Cohort 3: Third Line and Beyond Atezolizumab | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC3 or IC3 PFS | 4.2 months |
| Cohort 3: Third Line and Beyond Atezolizumab | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 PFS | 2.8 months |
| Cohorts 2 + 3 | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC3 or IC3 PFS | 4.1 months |
| Cohorts 2 + 3 | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC2/3 or IC2/3 PFS | 2.8 months |
| Cohorts 2 + 3 | Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 | TC3 or IC2/3 PFS | 2.8 months |
Secondary
Time in Response (TIR) as Assessed by INV Per RECIST v1.1
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.
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)
Population: Efficacy evaluable population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: First Line Atezolizumab | Time in Response (TIR) as Assessed by INV Per RECIST v1.1 | 0.033 months |
| Cohort 2: Second Line Atezolizumab | Time in Response (TIR) as Assessed by INV Per RECIST v1.1 | 0.033 months |
| Cohort 3: Third Line and Beyond Atezolizumab | Time in Response (TIR) as Assessed by INV Per RECIST v1.1 | 0.033 months |
| Cohorts 2 + 3 | Time in Response (TIR) as Assessed by INV Per RECIST v1.1 | 0.033 months |
Secondary
TIR as Assessed by INV Per Modified RECIST
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.
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)
Population: Efficacy evaluable population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: First Line Atezolizumab | TIR as Assessed by INV Per Modified RECIST | 0.033 months |
| Cohort 2: Second Line Atezolizumab | TIR as Assessed by INV Per Modified RECIST | 0.033 months |
| Cohort 3: Third Line and Beyond Atezolizumab | TIR as Assessed by INV Per Modified RECIST | 0.033 months |
| Cohorts 2 + 3 | TIR as Assessed by INV Per Modified RECIST | 0.033 months |
Secondary
TIR as Assessed by IRF Per RECIST v1.1
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.
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)
Population: Efficacy evaluable population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: First Line Atezolizumab | TIR as Assessed by IRF Per RECIST v1.1 | 0.033 months |
| Cohort 2: Second Line Atezolizumab | TIR as Assessed by IRF Per RECIST v1.1 | 0.033 months |
| Cohort 3: Third Line and Beyond Atezolizumab | TIR as Assessed by IRF Per RECIST v1.1 | 0.033 months |
| Cohorts 2 + 3 | TIR as Assessed by IRF Per RECIST v1.1 | 0.033 months |