A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer

Small Cell Lung Cancer Clinical Trial

— SKYSCRAPER-02  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04256421
• Other study ID #: GO41767
• Secondary ID: 2019-003301-97
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 4, 2020
• Est. completion date: April 15, 2026

Study information

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

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 490
• Est. completion date: April 15, 2026
• Est. primary completion date: September 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• Tiragolumab
Tiragolumab 600 milligrams (mg) administered by IV infusion on Day 1 of each 21-day cycle.
• Atezolizumab
Atezolizumab 1200 mg administered by IV infusion on Day 1 of each 21-day cycle.
• Carboplatin
Carboplatin was administered by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
• Etoposide
Etoposide 100 mg/m^2 administered by IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles.
• Placebo
Placebo administered by IV infusion on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Australia	Sunshine Coast University Hospital; The Adem Crosby Centre	Birtinya	Queensland
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Lyell McEwin Hospital; Oncology Clinical Trials, Chemotherapy Day Unit	Elizabeth Vale	South Australia
Australia	Nepean Hospital; Nepean Cancer Care Centre	Kingswood	New South Wales
Austria	Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie	Innsbruck
Austria	Klinik Penzing; Abteilung für Atemwegs- und Lungenkrankheiten	Wien
Austria	Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie	Wien
Belgium	AZ St Maarten Campus Leopoldstr	Mechelen
Belgium	Clinique Ste-Elisabeth	Namur
Belgium	AZ Delta (Campus Rumbeke)	Roeselare
Belgium	Vitaz	Sint Niklaas
Brazil	Clínica de Oncologia Reichow	Blumenau	SC
Brazil	Oncocentro Serviços Médicos e Hospitalares Ltda	Fortaleza	CE
Brazil	Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia	Passo Fundo	RS
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Czechia	Fakultni nemocnice Olomouc; Pneumologicka klinika	Olomouc
Czechia	Vitkovicka Nemocnice Bma, A.S.; Plicni Oddeleni	Ostrava
Czechia	Thomayerova nemocnice; Pneumologicka klinika 1.LF UK TN	Praha 4 - Krc
Germany	Helios Klinikum Emil von Behring GmbH	Berlin
Germany	Asklepios Klinik Gauting; Onkologisches Studienzentrum	Gauting
Germany	LungenClinic Großhansdorf GmbH; Klinische Forschung	Großhansdorf
Germany	Asklepios Klinik Harburg	Hamburg
Germany	Fachklinik für Lungenerkrankungen	Immenhausen
Germany	Universitätsklinikum Schleswig-Holstein; Campus Lübeck	Lübeck
Greece	General Hospital "G.Papanikolaou"; Pulmonogy Clinic	Asvestochori
Greece	Uoa Sotiria Hospital; Oncology	Athens
Greece	Metropolitan General Hospital	Cholargos
Greece	Univ General Hosp Heraklion; Medical Oncology	Heraklion
Hungary	Orszagos Koranyi TBC es Pulmonologiai Intezet	Budapest
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rend.Int.	Szolnok
Hungary	Tudogyogyintezet Torokbalint	Torokbalint
Italy	Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica	Bari	Puglia
Italy	Azienda Ospedaliero-Universitaria ?PoliclinicoVittorio Emanuele?- P.O. G. Rodolico; Oncologia Medica	Catania	Sicilia
Italy	AORN Ospedali dei Colli Ospedale Monaldi; UOC Pneumologia ad indirizzo Oncologico	Napoli	Campania
Italy	Azienda Sanitaria Ospedaliera S Luigi Gonzaga	Orbassano	Piemonte
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda	Padova	Veneto
Italy	AUSL della Romagna; Dipartimento Oncoematologico - U.O.C. Oncologia	Ravenna	Emilia-Romagna
Italy	IRCCS Istituto Clinico Humanitas; Oncologia	Rozzano (MI)	Lombardia
Italy	Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica	Siena	Toscana
Japan	National Cancer Center Hospital East	Chiba
Japan	Kyushu University Hospital	Fukuoka
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Kindai University Hospital	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	Saitama Cancer Center	Saitama
Japan	National Hospital Organization Kinki-Chuo Chest Medical Center	Sakai-shi
Japan	Shizuoka Cancer Center	Shizuoka
Japan	National Cancer Center Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Wakayama Medical University Hospital	Wakayama
Korea, Republic of	Chungbuk National University Hospital	Cheongju si
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Samsung Changwon Hospital	Gyeongsangnam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Ulsan University Hosiptal	Ulsan
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Erasmus MC	Rotterdam
New Zealand	Auckland City Hospital; Clinical Oncology	Auckland
Poland	Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny	Brzozów
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii	Gdansk
Poland	Krakowski Szpital Specjalistyczny im sw.Jana Pawla II	Krakow
Poland	Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii	Olsztyn
Poland	Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii	Otwock
Poland	Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu	Poznan
Poland	Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers	Warszawa
Russian Federation	BLOKHIN CANCER RESEARCH CENTER; CLINICAL ONCOLOGY; Clinical pharmacology and chemotheraphy	Moscow	Moskovskaja Oblast
Russian Federation	Principal Military Clinical Hospital n.a. N.N. Burdenko	Moscow	Moskovskaja Oblast
Russian Federation	Scientific Research Institute n.a. N.N. Petrov	Saint Petersburg	Sankt Petersburg
Serbia	Clinical Center of Serbia; Clinic for Pulmonary Diseases	Belgrade
Serbia	Clinical Hospital Center ''Bezanijska Kosa''; Department of Pulmology	Belgrade
Serbia	Institute for Pulmonary Diseases of Vojvodina; Clinic for Pulmonary Oncology	Sremska Kamenica
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore
Spain	Hospital Clinic Barcelona; Servicio de oncologia	Barcelona
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Fundacion Jimenez Diaz; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Clínico Universitario de Valencia; Servicio de Oncología	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia	Zaragoza
Switzerland	CHUV; Departement d'Oncologie	Lausanne
Switzerland	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich
Taiwan	National Cheng-Kung University Hospital	Tainan
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Chang-Gung Medical Foundation, Linkou Branch	Taoyuan
Taiwan	National Taiwan University Hospital; Oncology	Zhongzheng Dist.
Turkey	Adana Baskent University Hospital; Medical Oncology	Adana
Turkey	Ankara University Medical Faculty; Medikal Onkoloji	Ankara
Turkey	Gazi University Medical Faculty	Ankara
Turkey	Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty; Medikal Onkoloji Departmani	Istanbul
Turkey	Medipol University Medical Faculty; Oncology Department	Istanbul
Turkey	?zmir Medical Park; Onkoloji	Izmir
United Kingdom	NHS Lothian - Western General Hospital; NHS Lothian - Western General Hospital	Edinburgh
United Kingdom	Guys and St Thomas Hospital	London
United Kingdom	Christie Foundation Trust	Manchester
United Kingdom	Royal Marsden Hospital (Sutton)	Sutton
United Kingdom	Royal Cornwall Hospital	Truro
United States	Texas Oncology Cancer Center	Austin	Texas
United States	Weinberg Cancer Institution at Franklin Square	Baltimore	Maryland
United States	Broome Oncology - Binghamton	Binghamton	New York
United States	Sarah Cannon Research Institute / Tennessee Oncology	Chattanooga	Tennessee
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Florida Cancer Specialists; SCRI; Florida Cancer Specialists - Sarasota (Golf St)	Fort Myers	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Rocky Mountain Cancer Centers - Lone Tree	Lone Tree	Colorado
United States	University of Wisconsin School of Medicine and Public Health	Madison	Wisconsin
United States	Northwest Georgia Oncology Centers PC - Marietta	Marietta	Georgia
United States	SARAH CANNON RESEARCH INST.; Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai - PRIME; Icahn School of Medicine at Mount Sinai	New York	New York
United States	Illinois Cancer Care	Peoria	Illinois
United States	Blue Ridge Cancer Care	Roanoke	Virginia
United States	Minnesota Oncology Hematology	Saint Paul	Minnesota
United States	SCRI Florida Cancer Specialists North; Research Office North Region.	Saint Petersburg	Florida
United States	New England Cancer Specialists	Scarborough	Maine
United States	MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Czechia,  Germany,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Russian Federation,  Serbia,  Singapore,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigator-Assessed Progression Free Survival (PFS) in the Primary Analysis Set (PAS)		From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months)
Primary	Overall Survival (OS) in the PAS		From randomization to death from any cause (up to 50 months)
Secondary	PFS in the Full Analysis Set (FAS)		From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months)
Secondary	OS in the FAS		From randomization to death from any cause (up to 50 months)
Secondary	Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS		From randomization up to 50 months
Secondary	Investigator-Assessed Confirmed ORR in the FAS		From randomization up to 50 months
Secondary	Investigator-Assessed Duration of Response (DOR) in the PAS		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)
Secondary	Investigator-Assessed DOR in the FAS		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)
Secondary	Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS		6 months, 12 months
Secondary	Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS		6 months, 12 months
Secondary	Overall Survival Rates at 12 Months and 24 Months in the PAS		12 months, 24 months
Secondary	Overall Survival Rates at 12 Months and 24 Months in the FAS		12 months, 24 months
Secondary	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	TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS)/quality of life (QoL) and functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.	From randomization until the first confirmed clinically meaningful deterioration up to 50 months
Secondary	TTCD Assessed Using EORTC QLQ-C30 Score in the FAS	TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS)/quality of life (QoL) and functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.	From randomization until the first confirmed clinically meaningful deterioration up to 50 months
Secondary	Percentage of Participants With Adverse Events		Up to 50 months
Secondary	Minimum Serum Concentration (Cmin) of Tiragolumab		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)
Secondary	Cmin of Atezolizumab		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)
Secondary	Maximum Serum Concentration (Cmax) of Tiragolumab		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)
Secondary	Cmax of Atezolizumab		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)
Secondary	Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab		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)
Secondary	Percentage of Participants With ADAs to Atezolizumab		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)
Secondary	Change from Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Index-based and Visual Analog Scale Scores	The EQ-5D-5L is a validated self-report health status questionnaire that is used to calculate a health status utility score for use in health economic analyses. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a visual analog scale (VAS) that measures health state. A single composite score is calculated based on the responses as an indicator of the participant's health status.	From baseline up to 50 months