A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

NCT02763579 | Completed Phase 3 Results

• 2 other identifiers: GO300812015-004861-97
• Study Type: interventional
• Target: 503
• Locations: 20 countries
• Sites: 111

Brief Summary

This randomized, Phase I/III, multicenter, double-blinded, placebo-controlled study was designed to evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 \[PD-L1\] antibody) in combination with carboplatin plus (+) etoposide compared with treatment with placebo + carboplatin + etoposide in chemotherapy-naive participants with ES-SCLC. Participants will be randomized in a 1:1 ratio to receive either atezolizumab + carboplatin + etoposide or placebo + carboplatin + etoposide on 21-day cycles for four cycles in the induction phase followed by maintenance with atezolizumab or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD or symptomatic deterioration.

Conditions

Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (2)

• Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s).

  Baseline until PD or death, whichever occurs first (up to approximately 23 months)

• Duration of Overall Survival (OS) in the Global Population

  OS is defined as the time from randomization to death from any cause.

  Baseline until death from any cause (up to approximately 23 months)

Secondary Outcomes (11)

• Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

  Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months)

• Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

  First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months)

• PFS Rate at 6 Months and at 1 Year in Global Population

  6 months, 1 year

• OS Rate at 1 Year and 2 Years in the Global Population

  1 year, 2 years

• Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) and Supplemental Lung Cancer Module (QLQ-LC13) in the Global Population

  Baseline until deterioration per symptom subscale (up to approximately 23 months)

Study Arms (2)

Atezolizumab + Carboplatin + Etoposide

EXPERIMENTAL

Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Carboplatin; Drug: Etoposide

Placebo + Carboplatin + Etoposide

ACTIVE COMPARATOR

Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Drug: Carboplatin; Drug: Etoposide; Drug: Placebo

Interventions

Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody DRUG

Atezolizumab intravenous infusion was administered at a dose of 1200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Also known as: MPDL3280A, RO5541267, Tecentriq

Atezolizumab + Carboplatin + Etoposide

Carboplatin DRUG

Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).

Atezolizumab + Carboplatin + Etoposide; Placebo + Carboplatin + Etoposide

Etoposide DRUG

Etoposide intravenous infusion was administered at a dose of 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

Atezolizumab + Carboplatin + Etoposide; Placebo + Carboplatin + Etoposide

Placebo DRUG

Placebo intravenous infusion was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Placebo + Carboplatin + Etoposide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group \[VALG\] staging system)
• No prior systemic treatment for ES-SCLC
• Eastern Cooperative Oncology Group performance status of 0 or 1
• Measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end organ function
• Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC

You may not qualify if:

• Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation
• Malignancies other than SCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
• Pregnant or lactating women
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Positive test result for human immunodeficiency virus (HIV)
• Active hepatitis B or hepatitis C
• Severe infections at the time of randomization
• Significant cardiovascular disease
• Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1 (PD-1), and anti-PD-L1 therapeutic antibody
• History of severe (or known) hypersensitivity to chimeric or humanized antibodies or fusion proteins or any component of atezolizumab formulation.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (114)

Florida Cancer Specialists - Fort Myers (Broadway)

Fort Myers, Florida, 33901, United States

Location

Florida Hospital

Orlando, Florida, 32804, United States

Location

Florida Cancer Specialists.

St. Petersburg, Florida, 33705, United States

Location

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, 30060, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612-3244, United States

Location

Illinois Cancer Care

Peoria, Illinois, 61615, United States

Location

Cancer Treatment Centers of America - Midwestern Regional Medical Center

Zion, Illinois, 60099, United States

Location

Louisville Oncology

Louisville, Kentucky, 40202, United States

Location

New England Cancer Specialists

Scarborough, Maine, 04074, United States

Location

Weinberg CA Inst Franklin Sq

Baltimore, Maryland, 21237, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Comprehensive Cancer Centers of Nevada - Eastern Avenue

Las Vegas, Nevada, 89169, United States

Location

The Valley Hospital

Paramus, New Jersey, 07652, United States

Location

Broome Oncology - Binghamton

Binghamton, New York, 13905, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology PLLC - Nashville (20th Ave)

Nashville, Tennessee, 37203, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37232-7610, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Blue Ridge Cancer Care

Roanoke, Virginia, 24014, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

The Prince Charles Hospital; Oncology Dept.

Chermside, Queensland, 4032, Australia

Location

Royal Melbourne Hospital; Hematology and Medical Oncology

Parkville, Victoria, 3052, Australia

Location

Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Lungenkrankheiten

Linz, 4020, Austria

Location

Salzburger Landeskliniken; Universitätsklinik für Pneumologie/ Lungenheilkunde

Salzburg, 5020, Austria

Location

Klinik Penzing; Abteilung für Atemwegs- und Lungenkrankheiten

Vienna, 1140, Austria

Location

Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie

Vienna, 1210, Austria

Location

Santa Casa de Misericordia de Salvador

Salvador, Estado de Bahia, 40050-410, Brazil

Location

Hospital Bruno Born

Lajeado, Rio Grande do Sul, 95900-000, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Bradford Hill Centro de Investigaciones Clinicas

Recoleta, 8420383, Chile

Location

OrlandiOncología

Santiago, 7500713, Chile

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Jilin Cancer Hospital

Changchun, 132013, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510120, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Jiangsu Cancer Hospital

Nanjing, 211100, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Zhejiang Cancer Hospital

Zhejiang, 310022, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

Fakultni nemocnice Olomouc

Olomouc, 779 00, Czechia

Location

Fakultni nemocnice Na Bulovce

Prague, 180 81, Czechia

Location

Thomayerova nemocnice

Praha 4 - Krc, 140 59, Czechia

Location

Institut Bergonie; Oncologie

Bordeaux, 33076, France

Location

Centre Francois Baclesse; Oncologie

Caen, 14076, France

Location

Hopital Calmette; Pneumologie Oncologie Ouest

Lille, 59037, France

Location

Hôpital Nord - AP-HM Marseille#

Marseille, 13915, France

Location

Asklepios-Fachklinik Muenchen-Gauting; Klinik Für Pneumologie

Gauting, 82131, Germany

Location

LungenClinic Großhansdorf GmbH

Großhansdorf, 22927, Germany

Location

Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II

Halle, 06120, Germany

Location

Thoraxklinik Heidelberg gGmbH

Heidelberg, 69126, Germany

Location

Fachklinik für Lungenerkrankungen

Immenhausen, 34376, Germany

Location

Sotiria Chest Hospital of Athens

Athens, 11527, Greece

Location

Agioi Anargyroi; 3Rd Dept. of Medical Oncology

Athens, 145 64, Greece

Location

University Hospital of Patras Medical Oncology

Pátrai, 265 04, Greece

Location

Semmelweis Egyetem, AOK, Pulmonologiai Klinika

Budapest, 1083, Hungary

Location

Orszagos Koranyi TBC es Pulmonologiai Intezet

Budapest, 1121, Hungary

Location

Debreceni Egyetem, Klinikai Kozpont, Tudogyogyaszati Klinika

Debrecen, 4032, Hungary

Location

Tudogyogyintezet Torokbalint

Törökbálint, 2045, Hungary

Location

IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia

San Giovanni Rotondo, Apulia, 71013, Italy

Location

A.O. Universitaria Di Parma

Parma, Emilia-Romagna, 43100, Italy

Location

Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica

Rome, Lazio, 00128, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia

Milan, Lombardy, 20141, Italy

Location

Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare

Pisa, Tuscany, 56124, Italy

Location

Kyushu University Hospital; Respiratory

Fukuoka, 812-8582, Japan

Location

National Hospital Organization Himeji Medical Center

Hyōgo, 670-8520, Japan

Location

Kanagawa Cancer Center;Thoracic Oncology

Kanagawa, 241-8515, Japan

Location

University Hospital Kyoto Prefectural University of Medicine,?Pulmonary Medicine

Kyoto, 602-8566, Japan

Location

Sendai Kousei Hospital; Pulmonary Medicine

Miyagi, 980-0873, Japan

Location

Kurashiki Central Hospital; Respiratory Medicine

Okayama, 710-8602, Japan

Location

Kindai University Hospital; Medical Oncology

Osaka, 589-8511, Japan

Location

National Hospital Organization Kinki-Chuo Chest Medical Center; Internal Medicine

Osaka, 591-8555, Japan

Location

Saitama Cancer Center; Thoracic Oncology

Satima, 362-0806, Japan

Location

Shizuoka Cancer Center; Thoracic Oncology

Shizuoka, 411-8777, Japan

Location

Tokyo Metropolitan Komagome Hospital; Thoracic Oncology and Respiratory Medicine

Tokyo, 113-8677, Japan

Location

The Cancer Institute Hospital of JFCR, Respiratory Medicine

Tokyo, 135-8550, Japan

Location

Wakayama Medical University Hospital; Respiratory Medicine and Medical Oncology

Wakayama, 641-8509, Japan

Location

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), 03100, Mexico

Location

Medical University of Gdansk

Gdansk, 80-952, Poland

Location

Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi

Lodz, 93-513, Poland

Location

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc; Oddzial V Chemioterapii Nowotworow Pluc

Olsztyn, 10-357, Poland

Location

Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy

Otwock, 05-400, Poland

Location

Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu

Poznan, 60-569, Poland

Location

Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology

Warsaw, 02-781, Poland

Location

Moscow City Oncology Hospital #62

Moscovskaya Oblast, Moscow Oblast, 143423, Russia

Location

N.N.Burdenko Main Military Clinical Hospital; Oncology Dept

Moscow, Moscow Oblast, 105229, Russia

Location

Russian Oncology Research Center n.a. N.N. Blokhin

Moscow, Moscow Oblast, 115478, Russia

Location

Scientific Research Oncology Institute named after N.N. Petrov; Oncology

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

City Clinical Onc.

Saint Petersburg, Sankt-Peterburg, 198255, Russia

Location

City Clinical Hospital No. 1

Novosibirsk, 630047, Russia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Clinical Center Nis; Clinic for pulmonary diseases

Niš, 18 000, Serbia

Location

Seoul National University Bundang Hospital

Seongnam-si, 463-707, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Sant Andreu de la Barca, Barcelona, 08740, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, 28046, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

Málaga, 29010, Spain

Location

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, 41013, Spain

Location

Hosp Clinico Univ Lozano Blesa; División De Oncología Médica

Zaragoza, 50009, Spain

Location

National Taiwan Uni Hospital; Internal Medicine

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology

Taipei, 112, Taiwan

Location

Chang Gung Medical Foundation - Linkou; Chest Dept

Taoyuan District, 333, Taiwan

Location

Royal Devon & Exeter Hospital; Oncology Centre

Exeter, EX2 5DW, United Kingdom

Location

Barts and the London NHS Trust.

London, EC1A 7BE, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust, Guys Hospital

London, SE1 9RT, United Kingdom

Location

Christie Hospital Nhs Trust; Medical Oncology

Manchester, M2O 4BX, United Kingdom

Location

Related Publications (6)

• Bernabe R, Liu SV, Sanchez-Gastaldo A, Alonso Garcia M. Long-Term Survival and Stable Disease in a Patient with Extensive-Stage Small-Cell Lung Cancer after Treatment with Carboplatin, Etoposide and Atezolizumab. Oncol Ther. 2024 Mar;12(1):175-182. doi: 10.1007/s40487-023-00257-0. Epub 2024 Jan 27.

  PMID: 38280181 DERIVED

• Liu SV, Mok TSK, Nabet BY, Mansfield AS, De Boer R, Losonczy G, Sugawara S, Dziadziuszko R, Krzakowski M, Smolin A, Hochmair MJ, Garassino MC, Gay CM, Heymach JV, Byers LA, Lam S, Cardona A, Morris S, Adler L, Shames DS, Reck M. Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide. Lung Cancer. 2023 Dec;186:107418. doi: 10.1016/j.lungcan.2023.107418. Epub 2023 Oct 31.

  PMID: 37931445 DERIVED

• Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. doi: 10.1200/JCO.20.01055. Epub 2021 Jan 13.

  PMID: 33439693 DERIVED

• Mansfield AS, Kazarnowicz A, Karaseva N, Sanchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. doi: 10.1016/j.annonc.2019.10.021. Epub 2019 Dec 9.

  PMID: 31959349 DERIVED

• Nishio M, Sugawara S, Atagi S, Akamatsu H, Sakai H, Okamoto I, Takayama K, Hayashi H, Nakagawa Y, Kawakami T. Subgroup Analysis of Japanese Patients in a Phase III Study of Atezolizumab in Extensive-stage Small-cell Lung Cancer (IMpower133). Clin Lung Cancer. 2019 Nov;20(6):469-476.e1. doi: 10.1016/j.cllc.2019.07.005. Epub 2019 Jul 31.

  PMID: 31466854 DERIVED

• Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25.

  PMID: 30280641 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

atezolizumab; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2016
• First Posted: May 5, 2016
• Study Start: June 7, 2016
• Primary Completion: April 24, 2018
• Study Completion: July 7, 2022
• Last Updated: July 28, 2023
• Results First Posted: June 13, 2019

Record last verified: 2023-07

Locations

IT (6); PL (6); JP (13); ES (6); KR (4); CL (2); AU (4); GR (3); CN (9); RU (6); SE (2); GB (4); FR (4); ME (1); HU (4); CZ (3); US (22); DE (5); BR (4); TW (3)