A Randomized Phase 2 Study of Atezolizumab (an Engineered Anti-PDL1 Antibody) Compared With Docetaxel in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Failed Platinum Therapy - "POPLAR"

• ClinicalTrials.gov Identifier: NCT01903993
• Recruitment Status: Completed
• First Posted: July 19, 2013
• Results First Posted: May 23, 2017
• Last Update Posted: October 2, 2019
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: July 17, 2013
• First Posted Date: July 19, 2013
• Results First Submitted Date: November 16, 2016
• Results First Posted Date: May 23, 2017
• Last Update Posted Date: October 2, 2019
• Actual Study Start Date: August 6, 2013
• Actual Primary Completion Date: November 19, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 28, 2017)

Overall Survival (OS) [ Time Frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months) ]

Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive.

• Original Primary Outcome Measures (submitted: July 17, 2013): Overall survival [ Time Frame: approximately 3 years ]

Current Secondary Outcome Measures (submitted: July 28, 2017)

• Objective Response Rate (ORR) [ Time Frame: Baseline until date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months) ]
  ORR was defined as the percentage of participants with confirmed objective tumor response, complete response (CR) or partial response (PR), as determined by investigator using RECIST v1.1 criteria. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
• Progression-Free Survival (PFS) [ Time Frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months) ]
  PFS was defined as the time (in months) between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using response evaluation criteria In solid tumors (RECIST) v1.1. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions including baseline In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
• Duration of Response (DOR) [ Time Frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months) ]
  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 occurs first.
• ORR (Modified RECIST) [ Time Frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months) ]
  ORR was defined as the percentage of participants with confirmed objective tumor response, CR or PR, as determined by investigator using modified RECIST criteria. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to l< 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
• PFS (Modified RECIST) [ Time Frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months) ]
  PFS was defined as the time (in months) between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using modified RECIST criteria. PD: at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
• DOR (Modified RECIST) [ Time Frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months) ]
  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 occurs first.

Original Secondary Outcome Measures (submitted: July 17, 2013)

• Overall response (partial response plus complete response) according to RECIST v1.1 criteria [ Time Frame: approximately 1 year ]
• Progression-free survival, according to RECIST v1.1 criteria [ Time Frame: approximately 3 years ]
• Safety: Incidence of adverse events [ Time Frame: approximately 1 year ]
• Patient reported outcomes: EORTC QLQ-C30 and QLQ-LC12 questionnaires [ Time Frame: approximately 1 year ]

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

Descriptive Information

• Brief Title: A Randomized Phase 2 Study of Atezolizumab (an Engineered Anti-PDL1 Antibody) Compared With Docetaxel in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Failed Platinum Therapy - "POPLAR"
• Official Title: A Phase II, Open-label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of MPDL3280A (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Platinum Failure
• Brief Summary: This multicenter, open-label, randomized study will evaluate the efficacy and safety of Atezolizumab compared with docetaxel in participants with advanced or metastatic non-small cell lung cancer after platinum failure. Participants will be randomized to receive either Atezolizumab 1200 milligram (mg) intravenously every 3 weeks or docetaxel 75 milligram per meter square (mg/m^2) intravenously every 3 weeks. Treatment with Atezolizumab may be continued as long as participants are experiencing 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 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: Docetaxel
  Participants received starting dose of 75 mg/m^2 every three week (q3w) until disease progression, unacceptable toxicity or death. Dose modifications were according to the locally approved label. Participants randomized to receive docetaxel had to be premedicated with corticosteroids according to local practice.
• Drug: Atezolizumab
  Participants received atezolizumab of 1200 mg (equivalent to an average body weight-based dose of 15 milligram per kilogram [mg/kg]) which was administered by IV infusion q3w on Day 1 of each 21 day cycle. Participants were allowed to continue treatment beyond progression per response evaluation criteria in solid tumors (RECIST) v1.1 if they were experiencing clinical benefit per investigator, did not have a decline in performance status, did not have signs or symptoms of unequivocal progression, did not have tumor progression at critical sites, and signed an informed consent signature page acknowledging deferment any standard treatment options that may exist in favor of continuing atezolizumab.

Study Arms

• Active Comparator: Docetaxel
  Participants received docetaxel 75 milligram per meter square (mg/m^2) administered intravenously on Day 1 of each 21 day cycle until disease progression or unacceptable toxicity or death.
  Intervention: Drug: Docetaxel
• Experimental: Atezolizumab
  Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.
  Intervention: Drug: Atezolizumab

Publications *

• 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.
• Fehlings M, Jhunjhunwala S, Kowanetz M, O'Gorman WE, Hegde PS, Sumatoh H, Lee BH, Nardin A, Becht E, Flynn S, Ballinger M, Newell EW, Yadav M. Late-differentiated effector neoantigen-specific CD8+ T cells are enriched in peripheral blood of non-small cell lung carcinoma patients responding to atezolizumab treatment. J Immunother Cancer. 2019 Sep 12;7(1):249. doi: 10.1186/s40425-019-0695-9.
• Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. doi: 10.1016/S0140-6736(16)00587-0. Epub 2016 Mar 10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 11, 2015): 287
• Original Estimated Enrollment (submitted: July 17, 2013): 180
• Actual Study Completion Date: September 6, 2018
• Actual Primary Completion Date: November 19, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult participants, >/= 18 years of age
• Locally advanced or metastatic (Stage IIIB, Stage IV, or recurrent) non-small cell lung cancer (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
• Measurable disease, as defined by RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Known active or untreated central nervous system (CNS) metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments
• 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 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 CD137 agonists, anti-CTLA4, 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: Belgium, Canada, France, Germany, Italy, Korea, Republic of, Poland, Spain, Sweden, Thailand, Turkey, United Kingdom, United States
• Removed Location Countries: Hungary

Administrative Information

• NCT Number: NCT01903993
• Other Study ID Numbers: GO28753; 2013-001142-34 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• 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: September 2019