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"

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01903993
• Other study ID #: GO28753
• Secondary ID: 2013-001142-34
• Status: Completed
• Phase: Phase 2
• Start date: August 6, 2013
• Est. completion date: September 6, 2018

Study information

• Verified date: September 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 287
• Est. completion date: September 6, 2018
• Est. primary completion date: November 19, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• 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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Korea, Republic of,  Poland,  Spain,  Sweden,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	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.	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	Objective Response Rate (ORR)	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.	Baseline until date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)
Secondary	Progression-Free Survival (PFS)	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.	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	Duration of Response (DOR)	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.	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	ORR (Modified RECIST)	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.	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)
Secondary	PFS (Modified RECIST)	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.	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)
Secondary	DOR (Modified RECIST)	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.	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)