A Study of Atezolizumab Compared With Docetaxel in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Failed Platinum-Containing Therapy (OAK)

• ClinicalTrials.gov Identifier: NCT02008227
• Recruitment Status: Completed
• First Posted: December 11, 2013
• Results First Posted: July 2, 2017
• Last Update Posted: December 20, 2019
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: December 6, 2013
• First Posted Date: December 11, 2013
• Results First Submitted Date: May 8, 2017
• Results First Posted Date: July 2, 2017
• Last Update Posted Date: December 20, 2019
• Actual Study Start Date: March 11, 2014
• Actual Primary Completion Date: July 7, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 6, 2019)

• Percentage of Participants Who Died: PP-ITT [ Time Frame: Baseline until death due to any cause (up to approximately 2.25 years) ]
• Percentage of Participants Who Died: Tumor Cells (TC)1/2/3 or Tumor-Infiltrating Immune Cells (IC)1/2/3 Subgroup of PP [ Time Frame: Baseline until death due to any cause (up to approximately 2.25 years) ]
  Percentage of participants who died among TC1/2/3 or IC1/2/3 subgroup of PP-ITT were reported. TC1 = presence of discernible programmed death-ligand 1 (PD-L1) staining of any intensity in >/=1% and <5% TCs; TC2: presence of discernible PD-L1 staining of any intensity in >/=5% and <50% TCs; TC3 = presence of discernible PD-L1 staining of any intensity in >/=50% TCs; IC1 = presence of discernible PD-L1 staining of any intensity in ICs covering between >/=1% and <5% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma; IC2 = presence of discernible PD-L1 staining of any intensity in ICs covering between >/=5% and <10% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma; IC3 = presence of discernible PD-L1 staining of any intensity in ICs covering >/=10% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma.
• Overall Survival (OS): PP-ITT [ Time Frame: Baseline until death due to any cause (up to approximately 2.25 years) ]
  OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
• OS: TC1/2/3 or IC1/2/3 Subgroup of PP [ Time Frame: Baseline until death due to any cause (up to approximately 2.25 years) ]
  OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
• OS: SP-ITT [ Time Frame: Baseline until death due to any cause (up to approximately 2.87 years) ]
  OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
• OS: TC1/2/3 Or IC1/2/3 Subgroup of SP [ Time Frame: Baseline until death from any cause (approximately 2.87 years) ]
  OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
• OS: TC2/3 or IC2/3 Subgroup of SP [ Time Frame: Baseline until death due to any cause (up to approximately 2.87 years) ]
  OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
• OS: TC3 or IC3 Subgroup of SP [ Time Frame: Baseline until death due to any cause (up to approximately 2.87 years) ]
  OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.

• Original Primary Outcome Measures (submitted: December 6, 2013): Overall survival (OS) [ Time Frame: Approximately 4.5 years ]

Current Secondary Outcome Measures (submitted: December 6, 2019)

• Percentage of Participants With Disease Progression (PD) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death: PP-ITT [ Time Frame: Baseline up to PD or Death (up to approximately 2.25 years) ]
  PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 millimeters (mm), or presence of new lesions.
• Percentage of Participants With PD as Determined by Investigator Using RECIST v1.1 or Death: TC1/2/3 or IC1/2/3 Subgroup of PP [ Time Frame: Baseline up to PD or Death (up to approximately 2.25 years) ]
  PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, or presence of new lesions.
• Progression-Free Survival (PFS) as Determined by Investigator Using RECIST v1.1: PP-ITT [ Time Frame: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years) ]
  PFS is defined as the time between the date of randomization and the date of first documented PD or death, whichever occurs first. Participants who are alive and have not experienced PD at the time of analysis were censored at the time of the last tumor assessment. Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, or presence of new lesions.
• PFS as Determined by Investigator Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP [ Time Frame: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years) ]
  PFS is defined as the time between the date of randomization and the date of first documented PD or death, whichever occurs first. Participants who are alive and have not experienced PD at the time of analysis were censored at the time of the last tumor assessment. Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, or presence of new lesions.
• Percentage of Participants With Objective Response as Determined Using RECIST v1.1: PP-ITT [ Time Frame: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years) ]
  Objective response is defined as a complete response (CR) or partial response (PR) as determined by the Investigator using RECIST v1.1 on 2 consecutive occasions at least 6 weeks apart. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 mm). No new lesions. 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. No new lesions.
• Percentage of Participants With Objective Response as Determined Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP [ Time Frame: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years) ]
  Objective response is defined as a CR or PR as determined by the Investigator using RECIST v1.1 on 2 consecutive occasions at least 6 weeks apart. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. 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. No new lesions.
• Duration of Response (DOR) as Determined by Investigator Using RECIST v1.1: PP-ITT [ Time Frame: From first objective response of CR or PR to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years) ]
  DOR:Duration from the first tumor assessment that supports the participant's objective response to PD or death due to any cause,whichever occurs first.CR:complete disappearance of all target lesions and non-target disease.All nodes,both target and non-target,must decrease to normal. No new lesions.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.Participants who have not experienced PD at the time of analysis were censored at the time of the last tumor assessment.Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day.PD:at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm,progression of existing non-target lesions,or presence of new lesions.DOR was estimated using KM methodology.
• DOR as Determined by Investigator Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP [ Time Frame: From first objective response of CR or PR to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years) ]
  DOR:Duration from the first tumor assessment that supports the participant's objective response to PD or death due to any cause,whichever occurs first.CR:complete disappearance of all target lesions and non-target disease.All nodes,both target and non-target,must decrease to normal. No new lesions.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.Participants who have not experienced PD at the time of analysis were censored at the time of the last tumor assessment.Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day.PD:at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm,progression of existing non-target lesions,or presence of new lesions.DOR was estimated using KM methodology.
• Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab [ Time Frame: Baseline up to approximately 2.25 years (assessed at predose [Hour {Hr} 0] on Day 1 of Cycles 1, 2, 3, 4, 8, 16, then every 8 cycles up to end of treatment (EOT) [approximately 2.25 years]; 120 days after EOT [approximately 2.25 years] [1 Cycle=21 days]) ]
• Maximum Observed Serum Atezolizumab Concentration (Cmax) [ Time Frame: Predose (Hr 0), 30 minutes (min) post-infusion (infusion duration: 60 min) on Cycle 1 Day 1 (1 Cycle=21 days) ]
• Minimum Observed Serum Atezolizumab Concentration (Cmin) [ Time Frame: Predose (Hr 0) on Day 1 of Cycles 1, 2, 3, 4, 8, 16, 24, 32, EOT (approximately 2.25 years); 120 days after EOT (approximately 2.25 years) (1 Cycle=21 days) ]
• Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms, Using the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ) Lung Cancer Supplemental Module 13 (LC13) [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years) (1 Cycle = 21 days) ]
  TTD in patient-reported lung cancer symptoms (pain in chest or in arm/shoulder, dyspnea, or cough) was a composite endpoint defined as the time from randomization to the earliest time the participant's scale scores showed a 10 point or greater increase after baseline in any of the symptoms. A >/=10-point change in the score perceived by participants was considered as clinically significant. The QLQ-LC13 consisted of 1 multi-item scale and 9 single items that assessed the specific symptoms (dyspnea, cough, hemoptysis, and site specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of lung cancer participants receiving chemotherapy. Scale score range: 0 to 100. Higher symptom score = greater degree of symptom severity.
• EORTC QLQ Core 30 (C30) Questionnaire Score: Single Items [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  EORTC QLQ-C30 included global health status (GHS)/quality of life (QOL), functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement). Symptom scales/items were also linearly transformed so each score ranged 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement).
• EORTC QLQ-C30 Questionnaire Score: Functional Subscales [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  EORTC QLQ-C30 included GHS/QOL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement). Symptom scales/items were also linearly transformed so each score ranged 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement).
• EORTC QLQ-C30 Questionnaire Score: GHS Scale [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  EORTC QLQ-C30 included GHS/QOL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement). Symptom scales/items were also linearly transformed so each score ranged 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement).
• EORTC QLQ-C30 Questionnaire Score: Symptom Subscale [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  EORTC QLQ-C30 included GHS/QOL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement). Symptom scales/items were also linearly transformed so each score ranged 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement).
• EORTC QLQ-LC13 Questionnaire Score: Alopecia [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for alopecia.
• EORTC QLQ-LC13 Questionnaire Score: Coughing [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for coughing.
• EORTC QLQ-LC13 Questionnaire Score: Dysphagia [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for dysphagia.
• EORTC QLQ-LC13 Questionnaire Score: Dyspnea [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for dyspnea.
• EORTC QLQ-LC13 Questionnaire Score: Hemoptysis [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for hemoptysis.
• EORTC QLQ-LC13 Questionnaire Score: Pain in Arm or Shoulder [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for pain in arm or shoulder.
• EORTC QLQ-LC13 Questionnaire Score: Pain in Chest [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for pain in chest.
• EORTC QLQ-LC13 Questionnaire Score: Peripheral Neuropathy [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for peripheral neuropathy.
• EORTC QLQ-LC13 Questionnaire Score: Pain in Other Parts [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for pain in other parts.
• EORTC QLQ-LC13 Questionnaire Score: Sore Mouth [ Time Frame: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days) ]
  QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for sore mouth.
• PFS as Determined by Investigator Using RECIST v1.1: SP-ITT [ Time Frame: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.87 years) ]
  PFS is defined as the time between the date of randomization and the date of first documented PD or death, whichever occurs first. Participants who are alive and have not experienced PD at the time of analysis were censored at the time of the last tumor assessment. Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, or presence of new lesions.
• Percentage of Participants With Objective Response as Determined Using RECIST v1.1: SP-ITT [ Time Frame: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.87 years) ]
  Objective response is defined as a complete response (CR) or partial response (PR) as determined by the Investigator using RECIST v1.1 on 2 consecutive occasions at least 6 weeks apart. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 mm). No new lesions. 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. No new lesions.
• DOR as Determined by Investigator Using RECIST v1.1: SP ITT [ Time Frame: From first objective response of CR or PR to PD or death due to any cause, whichever occurred first (up to approximately 2.87 years) ]
  DOR:Duration from the first tumor assessment that supports the participant's objective response to PD or death due to any cause,whichever occurs first.CR:complete disappearance of all target lesions and non-target disease.All nodes,both target and non-target,must decrease to normal. No new lesions.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.Participants who have not experienced PD at the time of analysis were censored at the time of the last tumor assessment.Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day.PD:at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm,progression of existing non-target lesions,or presence of new lesions.DOR was estimated using KM methodology.

Original Secondary Outcome Measures (submitted: December 6, 2013)

• Overall response rate determined using Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) [ Time Frame: Up to 1 year ]
• Progression-free survival (PFS) evaluated with RECIST v. 1.1 [ Time Frame: Up to 1 year ]
• Duration of response evaluated with RECIST v. 1.1 [ Time Frame: Up to 1 year ]
• Incidence of adverse events [ Time Frame: Up to 1 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Atezolizumab Compared With Docetaxel in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Failed Platinum-Containing Therapy
• Official Title: A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Failure With Platinum Containing Chemotherapy
• Brief Summary: This global, multicenter, open-label, randomized, controlled study evaluated the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 [anti-PD-L1] antibody)compared with docetaxel in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure with platinum-containing chemotherapy. Participants were randomized 1:1 to receive either docetaxel or atezolizumab. Treatment may continue as long as participants experienced clinical benefit as assessed by the investigator, i.e., in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Squamous Non-Small Cell Lung Cancer

Intervention

• Drug: Atezolizumab
  1200 mg IV infusion on Day 1 of each 21-day cycle
  Other Name: Tecentriq
• Drug: Docetaxel
  75 mg/m^2 IV infusion on Day 1 of each 21-day cycle

Study Arms

• Experimental: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
  Atezolizumab 1200 milligrams (mg) was administered via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first.
  Intervention: Drug: Atezolizumab
• Active Comparator: Docetaxel
  Docetaxel 75 milligrams per meter square (mg/m^2) was administered via IV infusion on Day 1 of each 21-day cycle until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first.
  Intervention: Drug: Docetaxel

Publications *

• Cortellini A, Ricciuti B, Borghaei H, Naqash AR, D'Alessio A, Fulgenzi CAM, Addeo A, Banna GL, Pinato DJ. Differential prognostic effect of systemic inflammation in patients with non-small cell lung cancer treated with immunotherapy or chemotherapy: A post hoc analysis of the phase 3 OAK trial. Cancer. 2022 Aug 15;128(16):3067-3079. doi: 10.1002/cncr.34348. Epub 2022 Jun 21.
• Gadgeel S, Hirsch FR, Kerr K, Barlesi F, Park K, Rittmeyer A, Zou W, Bhatia N, Koeppen H, Paul SM, Shames D, Yi J, Matheny C, Ballinger M, McCleland M, Gandara DR. Comparison of SP142 and 22C3 Immunohistochemistry PD-L1 Assays for Clinical Efficacy of Atezolizumab in Non-Small Cell Lung Cancer: Results From the Randomized OAK Trial. Clin Lung Cancer. 2022 Jan;23(1):21-33. doi: 10.1016/j.cllc.2021.05.007. Epub 2021 May 30.
• Gandara D, Reck M, Moro-Sibilot D, Mazieres J, Gadgeel S, Morris S, Cardona A, Mendus D, Ballinger M, Rittmeyer A, Peters S. Fast progression in non-small cell lung cancer: results from the randomized phase III OAK study evaluating second-line atezolizumab versus docetaxel. J Immunother Cancer. 2021 Mar;9(3):e001882. doi: 10.1136/jitc-2020-001882.
• Shemesh CS, Chan P, Legrand FA, Shames DS, Das Thakur M, Shi J, Bailey L, Vadhavkar S, He X, Zhang W, Bruno R. Pan-cancer population pharmacokinetics and exposure-safety and -efficacy analyses of atezolizumab in patients with high tumor mutational burden. Pharmacol Res Perspect. 2020 Dec;8(6):e00685. doi: 10.1002/prp2.685.
• Chalabi M, Cardona A, Nagarkar DR, Dhawahir Scala A, Gandara DR, Rittmeyer A, Albert ML, Powles T, Kok M, Herrera FG; imCORE working group of early career investigators. Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials. Ann Oncol. 2020 Apr;31(4):525-531. doi: 10.1016/j.annonc.2020.01.006. Epub 2020 Jan 16.
• Morrissey KM, Marchand M, Patel H, Zhang R, Wu B, Phyllis Chan H, Mecke A, Girish S, Jin JY, Winter HR, Bruno R. Alternative dosing regimens for atezolizumab: an example of model-informed drug development in the postmarketing setting. Cancer Chemother Pharmacol. 2019 Dec;84(6):1257-1267. doi: 10.1007/s00280-019-03954-8. Epub 2019 Sep 21.
• Gadgeel SM, Lukas RV, Goldschmidt J, Conkling P, Park K, Cortinovis D, de Marinis F, Rittmeyer A, Patel JD, von Pawel J, O'Hear C, Lai C, Hu S, Ballinger M, Sandler A, Gandhi M, Fehrenbacher L. Atezolizumab in patients with advanced non-small cell lung cancer and history of asymptomatic, treated brain metastases: Exploratory analyses of the phase III OAK study. Lung Cancer. 2019 Feb;128:105-112. doi: 10.1016/j.lungcan.2018.12.017. Epub 2018 Dec 19.
• Bordoni R, Ciardiello F, von Pawel J, Cortinovis D, Karagiannis T, Ballinger M, Sandler A, Yu W, He P, Matheny C, Felizzi F, Rittmeyer A. Patient-Reported Outcomes in OAK: A Phase III Study of Atezolizumab Versus Docetaxel in Advanced Non-Small-cell Lung Cancer. Clin Lung Cancer. 2018 Sep;19(5):441-449.e4. doi: 10.1016/j.cllc.2018.05.011. Epub 2018 May 31.
• Hida T, Kaji R, Satouchi M, Ikeda N, Horiike A, Nokihara H, Seto T, Kawakami T, Nakagawa S, Kubo T. Atezolizumab in Japanese Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer: A Subgroup Analysis of the Phase 3 OAK Study. Clin Lung Cancer. 2018 Jul;19(4):e405-e415. doi: 10.1016/j.cllc.2018.01.004. Epub 2018 Feb 1.
• Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, De Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR; OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21;389(10066):255-265. doi: 10.1016/S0140-6736(16)32517-X. Epub 2016 Dec 13. Erratum In: Lancet. 2017 Apr 8;389(10077):e5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 29, 2015): 1225
• Original Estimated Enrollment (submitted: December 6, 2013): 850
• Actual Study Completion Date: January 9, 2019
• Actual Primary Completion Date: July 7, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Locally advanced or metastatic (Stage IIIB, Stage IV, or recurrent) NSCLC
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens
• Disease progression during or following treatment with a prior platinum-containing regimen for locally advanced, unresectable/inoperable or metastatic NSCLC or disease recurrence within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen or combined modality (e.g., chemoradiation) regimen with curative intent
• Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Known active or untreated central nervous system (CNS) metastases
• Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Active hepatitis B or hepatitis C
• Prior treatment with docetaxel
• Prior treatment with cluster of differentiation 137 (CD137) agonists, anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti-CTLA4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Austria, Brazil, Canada, Chile, Finland, France, Germany, Greece, Guatemala, Hungary, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Norway, Panama, Poland, Portugal, Russian Federation, Serbia, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Belgium, Mexico

Administrative Information

• NCT Number: NCT02008227
• Other Study ID Numbers: GO28915; 2013-003331-30 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: December 2019