Clinical trial NCT01903993: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-07-19
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 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)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Baseline until date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)
measure: Progression-Free Survival (PFS)
timeFrame: 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)
measure: Duration of Response (DOR)
timeFrame: 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)
measure: ORR (Modified RECIST)
timeFrame: 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)
measure: PFS (Modified RECIST)
timeFrame: 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)
measure: DOR (Modified RECIST)
timeFrame: 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)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Hot Springs
country: United States
facility: Genesis Cancer Center
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: San Marcos
country: United States
facility: Kaiser Permanente - San Marcos
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente - Vallejo
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers - Colorado Springs (Circle)
state: Colorado
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Atlanta
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois Cancer Care
state: Illinois
city: Scarborough
country: United States
facility: New England Cancer Specialists
state: Maine
city: Detroit
country: United States
facility: Karmanos Cancer Institute..
state: Michigan
city: Billings
country: United States
facility: Billings Clinic; Research Center
state: Montana
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Eastern Avenue
state: Nevada
city: Paramus
country: United States
facility: The Valley Hospital
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Binghamton
country: United States
facility: Broome Oncology - Binghamton
state: New York
city: Eugene
country: United States
facility: Willamette Valley Cancer Ctr - 520 Country Club
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Knoxville
country: United States
facility: Center for Biomedical Research LLC
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - South Austin
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A. - Fort Worth
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists - Vancouver
state: Washington
city: Walla Walla
country: United States
facility: Providence St. Mary Regional Cancer Center
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital & Clinics
state: Washington
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Liège
country: Belgium
facility: Chr de La Citadelle
city: Laval
country: Canada
facility: Cite de La Sante de Laval; Hemato-Oncologie
state: Quebec
city: Montreal
country: Canada
facility: McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
state: Quebec
city: Clermont-ferrand
country: France
facility: Hopital Gabriel Montpied; Service de Pneumologie
city: La Tronche
country: France
facility: Hôpital Nord Michallon; Pneumologie
city: Nancy
country: France
facility: Centre D'Oncologie de Gentilly; Oncology
city: St Brieuc
country: France
facility: Centre Hospitalier de Saint Brieuc - Hôpital Yves Le Foll; Pneumologie
city: Toulouse
country: France
facility: Hopital Larrey; Pneumologie
city: Gauting
country: Germany
facility: Asklepios-Fachkliniken Muenchen-Gauting; Onkologie
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II
city: Immenhausen
country: Germany
facility: Fachklinik für Lungenerkrankungen
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg; Klinik und Poliklinik für Innere Medizin II, Pneumologie
city: Avellino
country: Italy
facility: Citta Ospedaliera; Divisione Oncologia Medica
state: Campania
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele;Oncologia Medica
state: Lombardia
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center; Medical Oncology
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Centre; Division of Hematology/Oncology
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
city: Lodz
country: Poland
facility: Woj.Wielospecjalistyczne Centrum Onkologii i Traumatologii; Oddz.Hematologii Pododz.Chemioterapii
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital La Paz
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Oncologia
city: Linköping
country: Sweden
facility: Universitetssjukhuset Linköping; Lungmedicinkliniken
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital; Medical Oncology
city: Bangkok
country: Thailand
facility: Rajavithi Hospital; Division of Medical Oncology
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty; Medical Oncology Department
city: Istanbul
country: Turkey
facility: Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology
city: London
country: United Kingdom
facility: Royal Free Hospital; Dept of Oncology
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital; Medical Oncology.
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust; Medical Oncology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.