Clinical trial NCT04256421: A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab (Anti-Tigit Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-02-05
Enrollment: 490
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 study will evaluate the efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in participants with chemotherapy-naive extensive-stage small cell lung cancer (ES-SCLC). Eligible participants will be stratified by Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1), LDH (\</= upper limit of normal \[ULN\] vs. \> ULN), and presence or history of brain metastasis (yes vs. no) and randomly assigned in a 1:1 ratio to receive one of the following treatment regimens during induction phase:

* Arm A: Tiragolumab plus atezolizumab plus CE
* Arm B: Placebo plus atezolizumab plus CE

Following the induction phase, participants will continue maintenance therapy with either atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm B).


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC)
* No prior systemic treatment for ES-SCLC
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (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

Exclusion Criteria:

* Symptomatic or actively progressing central nervous system (CNS) metastases
* Malignancies other than small cell lung cancer (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
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Positive test result for human immunodeficiency virus (HIV)
* Active hepatitis B or hepatitis C
* Severe infection at the time of randomization
* Treatment with any other investigational agent within 28 days prior to initiation of study treatment
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4), anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives prior to randomization

Primary outcomes:
measure: Investigator-Assessed Progression Free Survival (PFS) in the Primary Analysis Set (PAS)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months)
measure: Overall Survival (OS) in the PAS
timeFrame: From randomization to death from any cause (up to 50 months)
Secondary outcomes:
measure: PFS in the Full Analysis Set (FAS)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months)
measure: OS in the FAS
timeFrame: From randomization to death from any cause (up to 50 months)
measure: Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS
timeFrame: From randomization up to 50 months
measure: Investigator-Assessed Confirmed ORR in the FAS
timeFrame: From randomization up to 50 months
measure: Investigator-Assessed Duration of Response (DOR) in the PAS
timeFrame: From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first (up to 50 months)
measure: Investigator-Assessed DOR in the FAS
timeFrame: From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first (up to 50 months)
measure: Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS
timeFrame: 6 months, 12 months
measure: Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS
timeFrame: 6 months, 12 months
measure: Overall Survival Rates at 12 Months and 24 Months in the PAS
timeFrame: 12 months, 24 months
measure: Overall Survival Rates at 12 Months and 24 Months in the FAS
timeFrame: 12 months, 24 months
measure: Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Score in the PAS
timeFrame: From randomization until the first confirmed clinically meaningful deterioration up to 50 months
measure: TTCD Assessed Using EORTC QLQ-C30 Score in the FAS
timeFrame: From randomization until the first confirmed clinically meaningful deterioration up to 50 months
measure: Percentage of Participants With Adverse Events
timeFrame: Up to 50 months
measure: Minimum Serum Concentration (Cmin) of Tiragolumab
timeFrame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at treatment discontinuation (TD) visit (up to 50 months)
measure: Cmin of Atezolizumab
timeFrame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months)
measure: Maximum Serum Concentration (Cmax) of Tiragolumab
timeFrame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months)
measure: Cmax of Atezolizumab
timeFrame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months)
measure: Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
timeFrame: Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months)
measure: Percentage of Participants With ADAs to Atezolizumab
timeFrame: Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months)
measure: Change from Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Index-based and Visual Analog Scale Scores
timeFrame: From baseline up to 50 months
Other outcomes:
Locations:
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers - Lone Tree
state: Colorado
city: Washington
country: United States
facility: MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Sarasota
country: United States
facility: SCRI Florida Cancer Specialists North
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC - Marietta
state: Georgia
city: Peoria
country: United States
facility: Illinois Cancer Care
state: Illinois
city: Scarborough
country: United States
facility: New England Cancer Specialists
state: Maine
city: Baltimore
country: United States
facility: Weinberg Cancer Institution at Franklin Square
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology
state: Minnesota
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chattanooga
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Inst.
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin School of Medicine and Public Health
state: Wisconsin
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Innsbruck
country: Austria
facility: Tiroler Landeskrankenanstalten Ges.M.B.H.
city: Wien
country: Austria
facility: Klinik Penzing
city: Wien
country: Austria
facility: Krankenhaus Nord - Klinik Floridsdorf
city: Mechelen
country: Belgium
facility: AZ St Maarten Campus Leopoldstr
city: Namur
country: Belgium
facility: Clinique Ste-Elisabeth
city: Roeselare
country: Belgium
facility: AZ Delta (Campus Rumbeke)
city: Sint Niklaas
country: Belgium
facility: Vitaz
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: Bahia
city: Fortaleza
country: Brazil
facility: Oncocentro Serviços Médicos e Hospitalares Ltda
state: Ceará
city: Passo Fundo
country: Brazil
facility: Hospital de Clínicas de Passo Fundo
state: Rio Grande Do Sul
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: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Ostrava
country: Czechia
facility: Vitkovicka Nemocnice Bma, A.S.
city: Praha 4 - Krc
country: Czechia
facility: Thomayerova nemocnice
city: Berlin
country: Germany
facility: Helios Klinikum Emil von Behring GmbH
city: Großhansdorf
country: Germany
facility: LungenClinic Großhansdorf GmbH
city: Hamburg
country: Germany
facility: Asklepios Klinik Harburg
city: Immenhausen
country: Germany
facility: Fachklinik für Lungenerkrankungen
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: München-Gauting
country: Germany
facility: Asklepios Klinik Gauting
city: Asvestochori
country: Greece
facility: General Hospital "G.Papanikolaou"
city: Athens
country: Greece
facility: Uoa Sotiria Hospital
city: Cholargos
country: Greece
facility: Metropolitan General Hospital
city: Heraklion
country: Greece
facility: Univ General Hosp Heraklion
city: Budapest
country: Hungary
facility: Orszagos Koranyi TBC es Pulmonologiai Intezet
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rend.Int.
city: Torokbalint
country: Hungary
facility: Tudogyogyintezet Torokbalint
city: Napoli
country: Italy
facility: AORN Ospedali dei Colli Ospedale Monaldi
state: Campania
city: Ravenna
country: Italy
facility: AUSL della Romagna
state: Emilia-Romagna
city: Rozzano
country: Italy
facility: IRCCS Istituto Clinico Humanitas
state: Lombardia
city: Orbassano
country: Italy
facility: Azienda Sanitaria Ospedaliera S Luigi Gonzaga
state: Piemonte
city: Bari
country: Italy
facility: Irccs Ist. Tumori Giovanni Paolo Ii
state: Puglia
city: Catania
country: Italy
facility: Azienda Ospedaliero-Universitaria ?PoliclinicoVittorio Emanuele?- P.O. G. Rodolico
state: Sicilia
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV)
state: Veneto
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Osaka
country: Japan
facility: NHO Kinki-Chuo Chest Medical Center
city: Saitama
country: Japan
facility: Saitama Cancer Center
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Gyeongsangnam-do
country: Korea, Republic of
facility: Samsung Changwon Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hosiptal
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Brzozow
country: Poland
facility: Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im sw.Jana Pawla II
city: Olsztyn
country: Poland
facility: Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu
city: Warszawa
country: Poland
facility: Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
city: Moscow
country: Russian Federation
facility: Principal Military Clinical Hospital n.a. N.N. Burdenko
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center
state: Moskovskaja Oblast
city: Saint Petersburg
country: Russian Federation
facility: Scientific Research Institute n.a. N.N. Petrov
state: Sankt Petersburg
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinical Hospital Center ''Bezanijska Kosa''
city: Sremska Kamenica
country: Serbia
facility: Institute for Pulmonary Diseases of Vojvodina
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Lausanne
country: Switzerland
facility: CHUV
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
city: Tainan
country: Taiwan
facility: National Cheng-Kung University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang-Gung Medical Foundation, Linkou Branch
city: Zhongzheng Dist.
country: Taiwan
facility: National Taiwan University Hospital
city: Adana
country: Turkey
facility: Adana Baskent University Hospital
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty
city: Istanbul
country: Turkey
facility: Medipol University Medical Faculty
city: Izm?r
country: Turkey
facility: ?zmir Medical Park
city: Edinburgh
country: United Kingdom
facility: NHS Lothian - Western General Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas Hospital
city: Manchester
country: United Kingdom
facility: Christie Foundation Trust
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: