Clinical trial NCT03456063: A Study of Neoadjuvant Atezolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (IMpower030)
Official title: A Phase III, Double-Blinded, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment With Atezolizumab or Placebo in Combination With Platinum-Based Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non-Small-Cell Lung
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-03-07
Enrollment: 453
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 is a randomized, double-blinded study designed to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of neoadjuvant treatment with atezolizumab (MPDL3280A) or placebo in combination with platinum-based chemotherapy in participants with resectable Stage II, IIIA, or select IIIB non-small cell lung cancer (NSCLC) followed by open-label adjuvant/postoperative atezolizumab or best supportive care and monitoring.


Eligibility criteria: Inclusion criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Histologically or cytologically confirmed, resectable Stage II, IIIA, or Select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on the 8th edition of the AJCC/UICC staging system
* Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent
* Adequate pulmonary and cardiac function to undergo surgical resection
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end organ function
* Negative HIV test at screening
* Negative for active HBV and HCV at screening
* Adequate tissue for PD-L1 IHC assessment

Exclusion criteria:

* NSCLC with histology of large cell neuroendocrine carcinoma or sarcomatoid carcinoma
* Mixed NSCLC and small cell lung cancer histology
* Any prior therapy for lung cancer
* Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated expected curative outcome
* Non-squamous NSCLC histology with activating ALK and EGFR mutation
* Pregnant or lactating women
* History of autoimmune disease
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or evidence of active of active pneumonitis on screening chest Computed Tomography (CT) scan
* Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
* Severe infection within 4 weeks prior to randomization
* Significant history of cardiovascular disease

Primary outcomes:
measure: Independent Review Facility (IRF)-Assessed Event Free Survival (EFS)
timeFrame: Up to approximately 96 months
Secondary outcomes:
measure: Pathological Complete Response (pCR)
timeFrame: At time of surgery
measure: Major Pathological Response (MPR)
timeFrame: At time of surgery
measure: Objective Response (OR)
timeFrame: Prior to surgery, up to approximately 84 days
measure: Overall Survival (OS)
timeFrame: Up to approximately 96 months
measure: Investigator-Assessed EFS
timeFrame: Up to approximately 96 months
measure: Disease-Free Survival (DFS)
timeFrame: Up to approximately 96 months
measure: 2-Year and 3-Year OS
timeFrame: Up to approximately 96 months
measure: 2-Year and 3-Year Independent Review Facility-Assessed EFS
timeFrame: Up to approximately 96 months
measure: 2-Year and 3-Year Investigator-Assessed EFS
timeFrame: Up to approximately 96 months
measure: Change from baseline in HRQoL scores
timeFrame: Up to approximately 96 months
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 96 months
measure: Number and Severity of Surgical Related Adverse Events
timeFrame: Up to approximately 96 months
measure: Number of Surgical Delays
timeFrame: Up to approximately 96 months
measure: Length of Surgical Delays
timeFrame: Up to approximately 96 months
measure: Number of Operative and Post-Operative Complications
timeFrame: Up to approximately 96 months
measure: Reasons for Surgical Cancellations
timeFrame: Up to approximately 96 months
measure: Minimum Observed Serum Atezolizumab Concentration (Cmin)
timeFrame: Pre-dose on Day 1 of Cycles 1 and 3 (each cylce is 21 days) for Neoadjuvant Treatment; pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 (each cycle is 21 days) for Arm A; at treatment or observation follow-up discontinuation (up to approximately 96 months)
measure: Maximum Observed Serum Atezolizumab Concentration (Cmax)
timeFrame: Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 96 months)
measure: Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab
timeFrame: Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 96 months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology
state: Arizona
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: Orange
country: United States
facility: The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
state: California
city: Sacramento
country: United States
facility: UC Davis Cancer Center
state: California
city: San Diego
country: United States
facility: Scripps Clinic
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: Washington Cancer Institute
state: District of Columbia
city: Peoria
country: United States
facility: Illinois Cancer Care
state: Illinois
city: Baltimore
country: United States
facility: Uni of Maryland Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Brighton
country: United States
facility: Brighton Center for Specialty Care
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Minneapolis
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Springfield
country: United States
facility: Mercy Clinic Cancer & Hematology
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Estabrook Cancer Center
state: Nebraska
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: Mineola
country: United States
facility: NYU Winthrop Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - South Austin
state: Texas
city: Tyler
country: United States
facility: UT Health East Texas HOPE Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists - Vancouver
state: Washington
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Linz
country: Austria
facility: Kepler Universitätskliniken GmbH - Med Campus III
city: Linz
country: Austria
facility: Ordensklinikum Linz Elisabethinen
city: Wien
country: Austria
facility: Klinik Penzing
city: Wien
country: Austria
facility: Krankenhaus Nord - Klinik Floridsdorf
city: Belo Horizonte
country: Brazil
facility: Cenantron - Centro Avancado de Tratamento Oncologico
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: São Paulo
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Angers
country: France
facility: CHU Angers
city: Lyon
country: France
facility: Centre Léon Bérard
city: Saint Quentin
country: France
facility: Centre Hospitalier Saint Quentin
city: Saint-Mande
country: France
facility: Hopital d'Instruction des Armees de Begin
city: Strasbourg
country: France
facility: CHU Strasbourg - Nouvel Hopital Civil
city: Toulon
country: France
facility: Hôpital d'Instruction des Armées de Sainte Anne
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Gauting
country: Germany
facility: Asklepios-Fachkliniken Muenchen-Gauting
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau gGmbH
city: Oldenburg
country: Germany
facility: Pius-Hospital Oldenburg
city: Regensburg
country: Germany
facility: Klinikum der Univer Regenburg
city: Stuttgart
country: Germany
facility: Robert Bosch Krankenhaus
city: Würzburg
country: Germany
facility: Missionsärztliche Klinik, Gemeinnützige Gesellschaft mbH
city: Budapest
country: Hungary
facility: Semmelweis Egyetem X
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Kfar-Saba
country: Israel
facility: Meir Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky / Ichilov Hospital
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
state: Lazio
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int)
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO)
state: Lombardia
city: Pisa
country: Italy
facility: A.O. Universitaria Pisana-Ospedale Cisanello
state: Toscana
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto - IRCCS
state: Veneto
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hyogo
country: Japan
facility: Kobe University Hospital
city: Hyogo
country: Japan
facility: Hyogo Medical University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Miyagi
country: Japan
facility: Fukushima Medical University Hospital
city: Miyagi
country: Japan
facility: Sendai Kousei Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Okayama
country: Japan
facility: Kurashiki Central Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: St. Vincent's Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Kraków
country: Poland
facility: Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II
city: Warszawa
country: Poland
facility: Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
city: Moscow
country: Russian Federation
facility: FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF
state: Moskovskaja Oblast
city: Saint-Petersburg
country: Russian Federation
facility: S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: Scientific Research Oncology Institute named after N.N. Petrov
state: Sankt Petersburg
city: Belgrade
country: Serbia
facility: University Hospital Medical Center Bezanijska kosa
city: Golnik
country: Slovenia
facility: University Clinic Golnik
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank
city: Pretoria
country: South Africa
facility: Eugene Marais Hospital
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
state: Barcelona
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
state: Islas Baleares
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario la Fe
city: Linköping
country: Sweden
facility: Lungmedicinska kliniken, Centrum för kirurgi, ortopedi och cancervård, Universitetssjukhuset
city: Lund
country: Sweden
facility: Uni Hospital in Lund
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset, Solna
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Lausanne
country: Switzerland
facility: CHUV
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
city: Xitun Dist.
country: Taiwan
facility: Taichung Veterans General Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital
city: ChiangMai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Dnipropetrovsk
country: Ukraine
facility: Chemotherapy SI Dnipropetrovsk MA of MOHU
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: London
country: United Kingdom
facility: Barts and the London NHS Trust.
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Romero Roman A, Campo-Canaveral de la Cruz JL, Macia I, Escobar Campuzano I, Figueroa Almanzar S, Delgado Roel M, Galvez Munoz C, Garcia Fontan EM, Muguruza Trueba I, Romero Vielva L, Cano Garcia JR, Martinez Tellez E, Partida Gonzalez C, Jimenez Lopez MF, Jimenez Maestre U, Mongil Poce R, Sanchez Lorente D, Alvarez Kindelan A, Provencio Pulla M. Outcomes of surgical resection after neoadjuvant chemoimmunotherapy in locally advanced stage IIIA non-small-cell lung cancer. Eur J Cardiothorac Surg. 2021 Jul 14;60(1):81-88. doi: 10.1093/ejcts/ezab007.