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)

Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03456063
• Other study ID #: GO40241
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 24, 2018
• Est. completion date: January 19, 2025

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 453
• Est. completion date: January 19, 2025
• Est. primary completion date: January 19, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Atezolizumab will be administered as intravenous (IV) infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle (every 3 weeks) for 4 cycles during the neoadjuvant treatment phase Atezolizumab will be administered as IV infusion at a dose of 1200 milligrams (mg) every 3 weeks for 16 cycles during the post-operative adjuvant phase
• Placebo Comparator
Placebo will be administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
• Nab-paclitaxel
Nab-paclitaxel 100 mg/m^2 will be administered intravenously on Days 1, 8, and 15 of each 21 day cycle for 4 cycles during the neoadjuvant treatment phase
• Pemetrexed
Pemetrexed 500 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
• Carboplatin
Carboplatin initial target AUC of 6 mg/mL/min will be administered intravenously on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
• Cisplatin
Cisplatin 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
• Gemcitabine
Gemcitabine 1250 mg/m^2 will be administered intravenously on Day 1 and 8 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase

Locations

Country	Name	City	State
Australia	Box Hill Hospital; Oncology	Box Hill	Victoria
Australia	St George Hospital; Cancer Care Centre	Kogarah	New South Wales
Australia	Peter MacCallum Cancer Center	North Melbourne	Victoria
Austria	Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Lungenkrankheiten	Linz
Austria	Ordensklinikum Linz Elisabethinen	Linz
Austria	Klinik Penzing; Abteilung für Atemwegs- und Lungenkrankheiten	Wien
Austria	Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie	Wien
Brazil	Cenantron - Centro Avancado de Tratamento Oncologico	Belo Horizonte	MG
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
China	Shanghai Chest Hospital	Shanghai
France	CHU Angers	Angers
France	Centre Léon Bérard	Lyon
France	Centre Hospitalier Saint Quentin	Saint Quentin
France	Hopital d'Instruction des Armees de Begin	Saint-Mande
France	CHU Strasbourg - Nouvel Hopital Civil	Strasbourg
France	Hôpital d'Instruction des Armées de Sainte Anne; Service de Pneumologie	Toulon
Germany	Universitätsklinikum Freiburg; Klinik für Innere Medizin I; Hämatologie/Onkologie	Freiburg
Germany	Asklepios-Fachkliniken Muenchen-Gauting; Onkologie	Gauting
Germany	Robert Bosch Krankenhaus; Pneumologie und pneumologische Onkologie	Gerlingen
Germany	LungenClinic Großhansdorf GmbH; Klinische Forschung	Großhansdorf
Germany	Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II	Halle
Germany	Pius-Hospital Oldenburg	Oldenburg
Germany	Klinikum der Univer Regenburg; Klinik und Poliklinik fuer Inn	Regensburg
Germany	Missionsärztliche Klinik, Gemeinnützige Gesellschaft mbH	Würzburg
Hungary	Semmelweis Egyetem X; Pulmonologiai Klinika	Budapest
Israel	Soroka Medical Center	Beer Sheva
Israel	Rambam Health Care Campus; Oncology	Haifa
Israel	Meir Medical Center; Oncology	Kfar-Saba
Israel	Sourasky / Ichilov Hospital; Dept. of Oncology	Tel Aviv
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica	Milano	Lombardia
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1	Milano	Lombardia
Italy	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto
Italy	A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii	Pisa	Toscana
Italy	Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica	Roma	Lazio
Japan	Aichi Cancer Center Hospital	Aichi
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Hiroshima City Hiroshima Citizens Hospital	Hiroshima
Japan	Hiroshima University Hospital	Hiroshima
Japan	Hyogo Medical University Hospital	Hyogo
Japan	Kobe University Hospital	Hyogo
Japan	Kyoto University Hospital	Kyoto
Japan	Sendai Kousei Hospital	Miyagi
Japan	Kurashiki Central Hospital	Okayama
Japan	Okayama University Hospital	Okayama
Japan	Osaka City General Hospital	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	Juntendo University Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Japan	Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital	Tokyo
Korea, Republic of	Kosin University Gospel Hospital	Busan
Korea, Republic of	St. Vincent's Hospital	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii	Gdansk
Poland	Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II; Oddz. Klin. Chir. Klatki Piersiowej i Onkol.	Kraków
Poland	Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers	Warszawa
Russian Federation	FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF	Moscow	Moskovskaja Oblast
Russian Federation	Main Military Clinical Hospital named after N.N. Burdenko	Moscow	Moskovskaja Oblast
Russian Federation	S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)	Saint-Petersburg	Sankt Petersburg
Russian Federation	Scientific Research Oncology Institute named after N.N. Petrov; Oncology	St. Petersburg	Sankt Petersburg
Serbia	University Hospital Medical Center Bezanijska kosa	Belgrade
Slovenia	University Clinic Golnik	Golnik
South Africa	Medical Oncology Centre of Rosebank; Oncology	Johannesburg
South Africa	Eugene Marais Hospital; Oncology	Pretoria
Spain	Hospital Universitari Vall d'Hebron; Oncology	Barcelona
Spain	Hospital de Basurto; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Clinica Universidad de Navarra Madrid; Servicio de Oncología	Madrid
Spain	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga
Spain	Hospital Son Llatzer; Servicio de Oncologia	Palma de Mallorca	Islas Baleares
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Spain	Hospital Universitario la Fe; Servicio de Oncologia	Valencia
Sweden	Lungmedicinska kliniken, Centrum för kirurgi, ortopedi och cancervård, Universitetssjukhuset	Linköping
Sweden	Uni Hospital in Lund; Respiratory Medicine & Allergology	Lund
Sweden	Karolinska Universitetssjukhuset, Solna; Kliniska prövningsenheten Z:4:01	Stockholm
Sweden	Uppsala University Hospital; Department of Oncology	Uppsala
Switzerland	CHUV; Departement d'Oncologie	Lausanne
Switzerland	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich
Taiwan	Kaohsiung Chang Gung Memorial Hospital; Dept of Internal Medicine	Kaohsiung
Taiwan	Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology	Taipei
Taiwan	Taichung Veterans General Hospital	Xitun Dist.
Thailand	Chulalongkorn Hospital; Medical Oncology	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital; Department of Medicine	ChiangMai
Ukraine	Chemotherapy SI Dnipropetrovsk MA of MOHU	Dnipropetrovsk
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Leeds Teaching Hosp NHS Trust;St James's Institute of Onc	Leeds
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool
United Kingdom	Barts and the London NHS Trust.	London
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	University of Michigan	Ann Arbor	Michigan
United States	University Of Colorado	Aurora	Colorado
United States	Texas Oncology - South Austin	Austin	Texas
United States	Uni of Maryland Cancer Center	Baltimore	Maryland
United States	Brighton Center for Specialty Care	Brighton	Michigan
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	National Jewish Health	Denver	Colorado
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Maine
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Northwell Health; Monter Cancer Center	Lake Success	New York
United States	USC Norris Cancer Center	Los Angeles	California
United States	NYU Winthrop Hospital	Mineola	New York
United States	Minnesota Oncology Minneapolis	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute / Tennessee Oncology	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	NYU Langone Medical Center; Laura and Isaac Perlmutter Cancer Center	New York	New York
United States	USC Norris Cancer Center; USC Oncology Hematology Newport Beach	Newport Beach	California
United States	Nebraska Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange	Orange	California
United States	Illinois Cancer Care	Peoria	Illinois
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	UC Davis Cancer Center; Oncology	Sacramento	California
United States	Scripps Clinic	San Diego	California
United States	Mercy Clinic Cancer & Hematology	Springfield	Missouri
United States	Arizona Oncology	Tucson	Arizona
United States	UT Health East Texas HOPE Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists - Vancouver	Vancouver	Washington
United States	Georgetown University	Washington	District of Columbia
United States	Washington Cancer Institute; Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  China,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Serbia,  Slovenia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Independent Review Facility (IRF)-Assessed Event Free Survival (EFS)	IRF-assessed EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, or death from any cause, whichever occurs first.	Up to approximately 96 months
Secondary	Pathological Complete Response (pCR)	pCR is defined as the absence of any viable primary tumor cells at the time of surgical resection in the primary tumor and all sampled lymph nodes as assessed by central and local pathology laboratory.	At time of surgery
Secondary	Major Pathological Response (MPR)	MPR is defined as = 10% residual viable tumor cells at the time of surgical resection in the primary tumor, as assessed by central and local pathology laboratory.	At time of surgery
Secondary	Objective Response (OR)	Objective response is defined as a complete response or partial response, as determined by the investigator according to RECIST v1.1	Prior to surgery, up to approximately 84 days
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death from any cause during the course of the study.	Up to approximately 96 months
Secondary	Investigator-Assessed EFS	EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, as assessed by the investigator; or death from any cause, whichever occurs first.	Up to approximately 96 months
Secondary	Disease-Free Survival (DFS)	DFS is defined as the time from the first date of no disease to local or distant recurrence (including occurrence of new primary NSCLC) or death due to any cause, whichever occurs first, as determined by the investigator during the adjuvant treatment and observation follow-up	Up to approximately 96 months
Secondary	2-Year and 3-Year OS	The 2-year and 3-year OS rate is defined as the probability that a participant will be alive 2 years and 3 years after randomization, respectively.	Up to approximately 96 months
Secondary	2-Year and 3-Year Independent Review Facility-Assessed EFS	EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Independent Review Facility.	Up to approximately 96 months
Secondary	2-Year and 3-Year Investigator-Assessed EFS	EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Investigator.	Up to approximately 96 months
Secondary	Change from baseline in HRQoL scores	Change from baseline in HRQoL scores as assessed through use of the two-item GHS/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30 at each assessment time point during the study through the completion of adjuvant treatment and observation follow-up assessments	Up to approximately 96 months
Secondary	Percentage of Participants With Adverse Events (AEs)		Up to approximately 96 months
Secondary	Number and Severity of Surgical Related Adverse Events		Up to approximately 96 months
Secondary	Number of Surgical Delays	Number of surgical delays.	Up to approximately 96 months
Secondary	Length of Surgical Delays	Length of surgical delays.	Up to approximately 96 months
Secondary	Number of Operative and Post-Operative Complications	Number of operative and post-operative complications.	Up to approximately 96 months
Secondary	Reasons for Surgical Cancellations	Reasons for surgical cancellations.	Up to approximately 96 months
Secondary	Minimum Observed Serum Atezolizumab Concentration (Cmin)	Cmin is the minimum (or trough) concentration that a study drug achieves in the body.	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)
Secondary	Maximum Observed Serum Atezolizumab Concentration (Cmax)	Cmax is the maximum (or peak) concentration that a study drug achieves in the body.	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)
Secondary	Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab		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)