A Study of Atezolizumab (Tecentriq) to Investigate Long-term Safety and Efficacy in Previously-treated Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

• Atezolizumab (Drug), also known as RO5541267, Tecentriq: Participants will receive 1200 milligrams (mg) of atezolizumab administered by intravenous infusion on Day 1 of every 3-week cycle until Investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or participant's decision to withdraw from therapy, or death (whichever occurs first).

Primary outcomes

• Percentage of Participants With Adverse Events [Baseline up to 4 years]: An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unitended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a pharmaceutical product whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as a AEs.

Secondary outcomes

• Percentage of Participants Alive 2 Years After Initiation of Treatment [Baseline up to Year 2]: The overall survival (OS) rate at 2 years, was defined as the percentage of participants remaining alive 2 years after initiation of study treatment.
• Overall Survival (OS) [Baseline up to death (up to 4 years)]: OS was defined as the time (in months) from initiation of study treatment to death from any cause.
• Progression-Free Survival (PFS) as Evaluated By the Investigator in Accordance With Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (v.1.1) [Baseline up to disease progression or death whichever occurs first (up to 4 years)]: PFS was defined as the time (in months) from initiation of study treatment to the first documented disease progression or death from any cause, whichever occurred first. PFS was evaluated by the investigator according to RECIST v1.1.
• EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire - Mobility Item [Day 1 of first 2 cycles (21-day cycle), then every 6 weeks for 54 weeks; thereafter every 3 weeks or 6 weeks until disease progression or until treatment discontinuation (up to 4 years)]: The EQ-5D-5L was a self-reported health status questionnaire that consisted of six questions used to calculate a health utility score for use in health economic analysis. The EQ-5D-5L has two components: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a Visual Analogue Scale (VAS) that measures health state. Each item was rated from 1 (no problems) to 5 (extreme problems). Categories with non-zero values are reported here. Number of participants who rated the mobility item ranging from 1-5 are reported. Participants who had a invalid response were presented under the category 'Invalid Response'.
• EQ-5D-5L Questionnaire - Self-Care Item [Day 1 of first 2 cycles (21-day cycle), then every 6 weeks for 54 weeks; thereafter every 3 weeks or 6 weeks until disease progression or until treatment discontinuation (up to 4 years)]: The EQ-5D-5L was a self-reported health status questionnaire that consisted of six questions used to calculate a health utility score for use in health economic analysis. The EQ-5D-5L has two components: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a VAS that measures health state. Each item was rated from 1 (no problems) to 5 (extreme problems). Categories with non-zero values are reported here. Number of participants who rated the self-care item ranging from 1-5 are reported. Participants who had a invalid response were presented under the category 'Invalid Response'.
• EQ-5D-5L Questionnaire - Usual Activities Item [Day 1 of first 2 cycles (21-day cycle), then every 6 weeks for 54 weeks; thereafter every 3 weeks or 6 weeks until disease progression or until treatment discontinuation (up to 4 years)]: The EQ-5D-5L was a self-reported health status questionnaire that consisted of six questions used to calculate a health utility score for use in health economic analysis. The EQ-5D-5L has two components: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a VAS that measures health state. Each item was rated from 1 (no problems) to 5 (extreme problems). Categories with non-zero values are reported here. Number of participants who rated the usual activities item ranging from 1-5 are reported. Participants who had a invalid response were presented under the category 'Invalid Response'.
• EQ-5D-5L Questionnaire - Pain/Discomfort Item [Day 1 of first 2 cycles (21-day cycle), then every 6 weeks for 54 weeks; thereafter every 3 weeks or 6 weeks until disease progression or until treatment discontinuation (up to 4 years)]: The EQ-5D-5L was a self-reported health status questionnaire that consisted of six questions used to calculate a health utility score for use in health economic analysis. The EQ-5D-5L has two components: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a VAS that measures health state. Each item was rated from 1 (no problems) to 5 (extreme problems). Categories with non-zero values are reported here. Number of participants who rated the pain/discomfort item ranging from 1-5 are reported. Participants who had a invalid response were presented under the category 'Invalid Response'.
• EQ-5D-5L Questionnaire - Anxiety/Depression Item [Day 1 of first 2 cycles (21-day cycle), then every 6 weeks for 54 weeks; thereafter every 3 weeks or 6 weeks until disease progression or until treatment discontinuation (up to 4 years)]: The EQ-5D-5L was a self-reported health status questionnaire that consisted of six questions used to calculate a health utility score for use in health economic analysis. The EQ-5D-5L has two components: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a VAS that measures health state. Each item was rated from 1 (no problems) to 5 (extreme problems). Categories with non-zero values are reported here. Number of participants who rated the anxiety/depression item ranging from 1-5 are reported. Participants who had a invalid response were presented under the category 'Invalid Response'.
• EQ-5D-5L Questionnaire - VAS Scores [Day 1 of first 2 cycles (21-day cycle), then every 6 weeks for 54 weeks; thereafter every 3 weeks or 6 weeks until disease progression or until treatment discontinuation (up to 4 years)]: The EQ-5D-5L was a self-reported health status questionnaire that consisted of six questions used to calculate a health utility score for use in health economic analysis. The EQ-5D-5L has two components: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a VAS that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. Values presented after baseline represent the change from baseline.
• European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Supplemental Lung Cancer Module (EORTC QLQ-LC13) [Day 1 of first 3 cycles (21-day cycle), then every 6 weeks for 48 weeks; thereafter every 9 weeks until disease progression or until treatment discontinuation (up to 4 years)]: The EORTC QLQ-LC13 consisted of 13 items that address key lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related adverse effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. The dysphagia scale is multi-item, while the rest are single-item scales. The scales are linearly transformed so that each score has a range from 0 to 100. A high scale score represents a higher response level (e.g. a high score for global health status represents a high QoL). A high score for the symptom scale represents a high level of symptoms. A >=10-point change in the EORTC scale score was perceived by participants as clinically significant. Values presented after baseline represent the change from baseline.
• Progression-Free Survival as Evaluated By the Investigator in Accordance With Modified RECIST [Baseline up to disease progression or death whichever occurs first (up to 4 years)]: PFS was defined as the time (in months) from initiation of study treatment to the first documented disease progression or death from any cause, whichever occurred first. PFS was evaluated by the investigator according to modified RECIST.
• Percentage of Participants Alive 3 Years After Initiation of Treatment [Baseline up to Year 3]: The OS rate at 3 years, was defined as the percentage of participants remaining alive 3 years after initiation of study treatment.
• Percentage of Participants With Objective Reponse as Assessed by the Investigator According to RECIST v1.1 [Baseline up to disease progression or death whichever occurs first (up to 4 years)]: Objective response rate (ORR), according to RECIST v1.1, was defined as the percentage of participants with a confirmed best overall response (BOR), either complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1.
• Percentage of Participants With Objective Reponse as Assessed by the Investigator According to Modified RECIST [Baseline up to disease progression or death whichever occurs first (up to 4 years)]: The investigator-assessed ORR was defined as the proportion of participants whose confirmed BOR is either a PR or CR per modified RECIST.
• Duration of Response as Assessed by the Investigator According to RECIST v.1.1 [From date of first objective response up to disease progression or death whichever occurs first (up to 4 years)]: DOR was defined as the time from the first tumor assessment that supported the participant's objective response (CR or PR, whichever was first reported) to documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred first, among participants who had a best overall response as CR or PR.
• Duration of Response as Assessed by the Investigator According to Modified RECIST [From date of first objective response up to disease progression or death whichever occurs first (up to 4 years)]: DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurred first.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Histologically or cytologically documented Stage IIIb or Stage IV NSCLC that has progressed following standard systemic chemotherapy (including if given in combination with anti-PD-1 therapy, after anti-PD-1 as monotherapy, or after TKI therapy). Participants with a previously detected sensitizing epidermal growth factor receptor (EGFR) mutation or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (ALK) fusion oncogene must have received targeted therapy (TKI) followed by at least one line of standard systemic chemotherapy prior to receiving atezolizumab. Overall, participants should not have received more than two lines of standard systemic chemotherapy. Participants who have discontinued first-line or second-line therapy due to intolerance are also eligible
* The last dose of prior systemic anticancer therapy or targeted therapy must have been administered more than or equal to (≥) 21 days prior to randomization.
* The last dose of prior anti-PD-1 therapy must have been administered. Nivolumab must have been discontinued >= 14 days and pembrolizumab >= 21 days prior to study treatment initiation, providing that these treatments were not administered in a clinical trial setting.
* Measurable disease, as defined by Response Evaluation Criteria for Solid Tumors, Version 1.1 (RECIST v1.1)
* Participants with asymptomatic central nervous system (CNS) metastases (treated or untreated), as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic evaluation, are eligible
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Life expectancy ≥ 12 weeks
* Adequate hematologic and end-organ function
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab
* Participants must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and toxicities related to prior anti-PD-1-therapy

Exclusion Criteria:

* Symptomatic CNS metastases
* Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ≥ 2 weeks prior to study treatment initiation
* Leptomeningeal disease
* Uncontrolled pericardial effusion or ascites requiring recurrent drainage procedures
* Pregnant or lactating, or intending to become pregnant during the study
* Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
* Significant cardiovascular disease, such as New York Heart Association cardiac disease ≥ Class III, myocardial infarction within 3 months, unstable arrhythmias, or unstable angina
* Significant renal disorder requiring dialysis or indication for renal transplant
* Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to study treatment initiation
* Major surgical procedure within 4 weeks prior to study treatment initiation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
* Inability to understand the local language(s) for which the EORTC QLQ-LC13 and EQ-5D-5L questionnaires are available
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
* History of autoimmune disease are allowed if controlled and on stable treatment (i.e., same treatment, same dose) for the last 12 weeks
* Prior allogeneic stem cell or solid organ transplantation
* History of idiopathic pulmonary fibrosis, including pneumonitis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
* Active tuberculosis
* Administration of a live, attenuated vaccine within 4 weeks prior to study treatment initiation
* Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies other than anti-PD-1 therapy, including anti-programmed death-ligand 1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents (including, but not limited to, interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to initiation of study treatment
* Specifically for participants without autoimmune disease: treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to study treatment initiation, or anticipated requirement for systemic immunosuppressive medications during the trial. For participants with CNS metastases, use of prednisone at a stable dose (or dose equivalent) of <= 20 mg/day is acceptable.

Participant flow

Outcome results

• Percentage of Participants With Adverse Events (Primary), Count of participants, Participants: Atezolizumab 564
• Percentage of Participants Alive 2 Years After Initiation of Treatment (Secondary), Number, Percentage of Participants: Atezolizumab 26.7
• Overall Survival (OS) (Secondary), Median, Months: Atezolizumab 11.2 (8.9 to 12.7)
• Progression-Free Survival (PFS) as Evaluated By the Investigator in Accordance With Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (v.1.1) (Secondary), Median, Months: Atezolizumab 2.7 (2.3 to 2.8)
• EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire - Mobility Item (Secondary), Count of participants, Participants: Atezolizumab 328
• EQ-5D-5L Questionnaire - Self-Care Item (Secondary), Count of participants, Participants: Atezolizumab 475
• EQ-5D-5L Questionnaire - Usual Activities Item (Secondary), Count of participants, Participants: Atezolizumab 297
• EQ-5D-5L Questionnaire - Pain/Discomfort Item (Secondary), Count of participants, Participants: Atezolizumab 206
• EQ-5D-5L Questionnaire - Anxiety/Depression Item (Secondary), Count of participants, Participants: Atezolizumab 334
• EQ-5D-5L Questionnaire - VAS Scores (Secondary), Mean, score on a scale: Atezolizumab -0.51 +/- 13.61
• European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Supplemental Lung Cancer Module (EORTC QLQ-LC13) (Secondary), Mean, Units on a scale: Atezolizumab 24.82 +/- 21.64
• Progression-Free Survival as Evaluated By the Investigator in Accordance With Modified RECIST (Secondary), Median, Months: Atezolizumab 3.7 (3.0 to 4.2)
• Percentage of Participants Alive 3 Years After Initiation of Treatment (Secondary), Number, Percentage of Participants: Atezolizumab 19.6
• Percentage of Participants With Objective Reponse as Assessed by the Investigator According to RECIST v1.1 (Secondary), Number, Percentage of Participants: Atezolizumab 11.5
• Percentage of Participants With Objective Reponse as Assessed by the Investigator According to Modified RECIST (Secondary), Number, Percentage of Participants: Atezolizumab 12.4
• Duration of Response as Assessed by the Investigator According to RECIST v.1.1 (Secondary), Median, Months: Atezolizumab 16.6 (9.7 to 20.3)
• Duration of Response as Assessed by the Investigator According to Modified RECIST (Secondary), Median, Months: Atezolizumab 20.5 (16.6 to 28.8)

Adverse events

Time frame: Baseline up to 4 years

Serious adverse events by term

85 more terms not shown.

Other adverse events by term

11 more sites not listed.

• Results publication: Ardizzoni A, Azevedo S, Rubio-Viqueira B, Rodriguez-Abreu D, Alatorre-Alexander J, Smit HJM, Yu J, Syrigos K, Hoglander E, Kaul M, Tolson J, Hu Y, Vollan HK, Newsom-Davis T. Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. J Immunother Cancer. 2022 Nov;10(11):e005581. doi: 10.1136/jitc-2022-005581. PMID 36450379
• Results publication: Ardizzoni A, Azevedo S, Rubio-Viqueira B, Rodriguez-Abreu D, Alatorre-Alexander J, Smit HJM, Yu J, Syrigos K, Trunzer K, Patel H, Tolson J, Cardona A, Perez-Moreno PD, Newsom-Davis T. Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer. J Immunother Cancer. 2021 Mar;9(3):e001865. doi: 10.1136/jitc-2020-001865. PMID 33737339

• Study Protocol (PDF, 2021-03-23)
• Statistical Analysis Plan (PDF, 2019-07-17)

NIH grants: 2017