A Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Participants With Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

— SKYSCRAPER-06  

Official title:

A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Patients With Previously Untreated Advanced Non-Squamous Non-Small-Cell Lung Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04619797
• Other study ID #: BO42592
• Secondary ID: 2020-002851-39
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: December 14, 2020
• Est. completion date: May 14, 2027

Study information

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

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin (Arm A) compared with placebo in combination with pembrolizumab plus pemetrexed and carboplatin/cisplatin (Arm B) in participants with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC). Eligible participants will be randomized in a 1:1 ratio to receive one of the following treatment regimens during the induction phase: - Arm A: Tiragolumab plus atezolizumab plus pemetrexed and carboplatin or cisplatin - Arm B: Placebo plus pembrolizumab plus pemetrexed and carboplatin or cisplatin Following the induction phase, participants will continue maintenance therapy with either tiragolumab in combination with atezolizumab and pemetrexed (Arm A) or placebo in combination with pembrolizumab and pemetrexed (Arm B).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 542
• Est. completion date: May 14, 2027
• Est. primary completion date: May 14, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
• No prior systemic treatment for metastatic non-squamous NSCLC
• Known tumor programmed death-ligand 1 (PD-L1) status
• Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
• Life expectancy >= 12 weeks
• Adequate hematologic and end-organ function
• Negative human immunodeficiency virus (HIV) test at screening
• Serology test negative for active hepatitis B virus or active hepatitis C virus at screening.

Key Exclusion Criteria:

• Mutations in epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) fusion oncogene
• Pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• 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
• History of malignancy other than NSCLC within 5 years prior to randomization, with the exception of malignancies with a negligible risk of metastasis or death
• Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 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 (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
• Known allergy or hypersensitivity or other contraindication to any component of the chemotherapy regimen the participant may receive during the study
• Women who are pregnant, or breastfeeding
• Known targetable c-ROS oncogene 1 (ROS1) or BRAFV600E genomic aberration.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• Tiragolumab
Tiragolumab at a fixed dose of 600 milligrams (mg), administered by intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
• Atezolizumab
Atezolizumab at a fixed dose of 1200 mg, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.
• Pemetrexed
Pemetrexed 500 milligrams per square meter (mg/m^2), administered by IV infusion, Q3W on Day 1 of each 21-day cycle.
• Carboplatin
Carboplatin at dose of area under the concentration-time curve (AUC) of 5, administered by IV infusion, Q3W on Day 1 of each 21-day cycle for 4 cycles.
• Cisplatin
Cisplatin 75 mg/m^2, administered by IV infusion, Q3W on Day 1 of each 21-day cycle for 4 cycles.
• Tiragolumab Matching Placebo
Matching placebo, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.
• Pembrolizumab
Pembrolizumab at a fixed dose of 200 mg, administered by IV infusion, Q3W, on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Belgium	Onze Lieve Vrouwziekenhuis Aalst	Aalst
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	CHU UCL Mont-Godinne	Mont-godinne
Belgium	Vitaz	Sint Niklaas
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Crio - Centro Regional Integrado de Oncologia	Fortaleza	CE
Brazil	Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda	Ijui	RS
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Victoria Hospital - London Health Sciences Centre	London	Ontario
Canada	Universite de Montreal - Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Sault Area Hospital; Algoma District Cancer Program	Sault Ste. Marie	Ontario
China	Beijing Cancer Hospital	Beijing
China	Jilin Cancer Hospital	Changchun
China	Xiangya Hospital Central South University	Changsha City
China	Changzhou First People's Hospital; Oncology	Changzhou
China	Affiliated Hospital of Chengde Medical University	Chengde City
China	Sichuan Cancer Hospital	Chengdu City
China	West China Hospital - Sichuan University	Chengdu City
China	Dongguan People's Hospital	Dongguan
China	Anhui Provincial Hospital; Respiratory Department	Hefei
China	Jinan Central Hospital	Jinan City
China	Linyishi Cancer Hospital	Linyi City
China	Pingxiang People Hospital	Pingxiang City
China	Qingdao Central Hospital; Department of Respiratory and Critical Care Medicine	Qingdao City
China	Weifang People's Hospital	Weifang City
China	Hubei Cancer Hospital	Wuhan
China	The First Affiliated Hospital of Xian Jiao Tong University	Xi'an City
China	The First Affiliated Hospital of Xinxiang Medical University	Xinxiang City
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou
Denmark	Rigshospitalet; Onkologisk Klinik	København Ø
Denmark	Odense Universitetshospital, Onkologisk Afdeling R	Odense C
Denmark	Sjællands Universitetshospital, Roskilde; Klinisk Onkologisk Afdeling og Palliativ Enhed	Roskilde
France	Institut Bergonie; Pneumology	Bordeaux
France	Hopital Nord; Pneumologie	Marseille cedex 20
France	Hopital de Pontchaillou; Service de Pneumologie	Rennes
France	CHU Strasbourg - Nouvel Hopital Civil	Strasbourg
France	CHU de Toulouse - Hôpital Larrey; Service de pneumologie et oncologie pneumologique	Toulouse cedex 9
Germany	Helios Klinikum Emil von Behring GmbH	Berlin
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	St. Vincentius Kliniken Karlsruhe	Karlsruhe
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie	Mainz
Germany	Klinikum der Philipps-Universität Marburg	Marburg
Hong Kong	Hong Kong United Oncology Centre	Hong Kong
Hong Kong	Queen Mary Hospital; Dept. of Clinical Oncology	Hong Kong
Hong Kong	Queen Mary Hospital; Medicine & Respiratory	Hong Kong
Hong Kong	Tuen Mun Hospital; Clinical Onc	Hong Kong
Hong Kong	Prince of Wales Hospital; Department of Clinical Onocology	Shatin
Italy	Centro Di Riferimento Oncologico; Struttura Operativa Complessa Di Oncologia Medica B	Aviano	Friuli-Venezia Giulia
Italy	Asst Papa Giovanni XXIII; Oncologia Medica	Bergamo	Lombardia
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna
Italy	ASST Spedali Civili di Brescia	Brescia	Lombardia
Italy	Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1	Firenze	Toscana
Italy	A.O. Villa Scassi; Oncologia Medica	Genova	Liguria
Japan	Kurume University Hospital	Fukuoka
Japan	Kyushu University Hospital	Fukuoka
Japan	Hiroshima University Hospital	Hiroshima
Japan	Takarazuka City Hospital	Hyogo
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto
Japan	Sendai Kousei Hospital	Miyagi
Japan	Kansai Medical University Hospital	Osaka
Japan	Kindai University Hospital	Osaka
Japan	NHO Kinki Chuo Chest Medical Center	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	Saitama Cancer Center	Saitama
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Tokyo Medical University Hachioji Medical Center	Tokyo
Japan	Wakayama Medical University Hospital	Wakayama
Korea, Republic of	Kosin University Gospel Hospital	Busan
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	St. Vincent's Hospital	Gyeonggi-do
Korea, Republic of	Samsung Changwon Hospital	Gyeongsangnam-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	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
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	ARKE Estudios Clínicos S.A. de C.V.	Ciudad de México
Mexico	Cuidados oncologicos	Querétaro	Queretaro
Mexico	Oncologico Potosino	San Luis Potosí	SAN LUIS Potosi
New Zealand	Auckland City Hospital, Cancer and Blood Research	Auckland
New Zealand	Waikato Hospital - Cancer and Blood Research Trials Unit; Regional Cancer Centre	Hamilton
New Zealand	Palmerston North Hospital	Palmerston North
New Zealand	Tauranga Hospital, Clinical Trials Unit; BOP Clinical School	Tauranga
Poland	Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna	?ód?
Poland	Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii	Olsztyn
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña
Spain	Hospital Clinic Barcelona; Servicio de oncologia	Barcelona
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	ICO L'Hospitalet; Servicio de oncologia medica	L'Hospitalet de Llobregat	Barcelona
Spain	Complejo Hospitalario Universitario Insular?Materno Infantil; Servicio de Oncologia	Las Palmas de Gran Canaria	LAS Palmas
Spain	Hospital Lucus Augusti; Servicio de Oncologia	Lugo
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Son Llatzer; Servicio de Oncologia	Palma de Mallorca	Islas Baleares
Spain	Hospital Univ. Nuestra Señora de Valme; Servicio de Oncologia	Sevilla
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie	Chur
Switzerland	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich
Taiwan	Changhua Christian Hospital	Chang Hua
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taipei Veterans General Hospital	Taipei City
Thailand	Chulalongkorn Hospital; Medical Oncology	Bangkok
Thailand	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok
Thailand	Pramongkutklao Hospital; Medicine - Medical Oncology Unit	Bangkok
Thailand	Vajira Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital; Department of Medicine	ChiangMai
Thailand	Songklanagarind Hospital; Department of Internal Medicine, Division of Respiratory	Songkhla
Turkey	Adana Baskent University Medical Faculty; Oncology	Adana
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Liv Hospital Ankara; Medical Oncology	Ankara
Turkey	Dicle University Faculty of Medicine	Diyarbakir
Turkey	Trakya University Medical Faculty	Edirne
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Medeniyet University Goztepe Training and Research Hospital.	Kadiköy
United Kingdom	Royal Cornwall Hospital; Dept of Clinical Oncology	Cornwall
United Kingdom	Castle Hill Hospital; The Queen's Centre for Oncology & Haematology	Hull
United Kingdom	Barts & London School of Med; Medical Oncology	London
United Kingdom	Guy'S Hospital; Oncology Unit	London
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	New Cross Hospital	Wolverhampton
United States	Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	Inova Schar Cancer Institute; Inova Schar Cancer Institute Infusion Pharmacy	Fairfax	Virginia
United States	SCRI Florida Cancer Specialists South	Fort Myers	Florida
United States	Fort Wayne Medical Oncology and Hematology, Inc	Fort Wayne	Indiana
United States	Baptist Health Lexington	Lexington	Kentucky
United States	UCLA	Los Angeles	California
United States	Northwest Georgia Oncology Centers PC - Marietta	Marietta	Georgia
United States	Sarah Cannon Research Institute / Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Advent Health Orlando	Orlando	Florida
United States	SCRI Florida Cancer Specialists North; Research Office North Region.	Saint Petersburg	Florida
United States	Torrance Memorial Physician Network/Cancer Care	Torrance	California
United States	PIH Health Whittier Hospital; NC	Whittier	California
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  China,  Denmark,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Mexico,  New Zealand,  Poland,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigator-Assessed Confirmed Objective Response Rate (ORR) (Phase 2)		Up to approximately 5 years
Primary	Investigator-Assessed Progression-Free Survival (PFS) (Phase 2 and Phase 3)		From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years [Phase 2], up to approximately 7 years [Phase 3])
Primary	Overall Survival (Phase 3)		From randomization to death from any cause (up to approximately 7 years)
Secondary	Overall Survival (Phase 2)		From randomization to death from any cause (up to approximately 5 years)
Secondary	PFS as Determined by an Independent Review Facility (IRF) (Phase 3)		From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 7 years)
Secondary	Investigator-assessed PFS in Participants With PD-L1 Expression at TC =50% and TC =1% Cut-off, as Determined by Central Testing With Ventana PD-L1 (SP263) Assay (Phase 3)		From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 7 years)
Secondary	OS in Participants With PD-L1 Expression at TC =50% and TC =1% Cut-off, as Determined by Central Testing With Ventana PD-L1 (SP263) Assay (Phase 3)		From randomization to death from any cause (up to approximately 7 years)
Secondary	Investigator-Assessed PFS at 6 Months and 12 Months (Phase 3)		6 months, 12 months
Secondary	OS Rate at 12 Months and 24 Months (Phase 3)		12 months, 24 months
Secondary	Investigator-Assessed Confirmed ORR (Phase 3)		Up to approximately 7 years
Secondary	Investigator-Assessed Duration of Response (DOR) (Phase 2 and Phase 3)		From first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years [Phase 2]; up to approximately 7 years [Phase 3])
Secondary	Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning and Global Health Status (GHS)/Quality of Life (QoL) as Measured by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (Phase 2 and Phase 3)	TTCD using EORTC Quality-of-Life Questionnaire Core 30 (QLQ-C30) is an initial 10-point decrease in GHS and physical 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/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.	Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
Secondary	TTCD in Participant-Reported Lung Cancer Symptoms for Cough, Dyspnea, and Chest Pain, as Measured by EORTC QLQ-LC13 (Phase 2 and Phase 3)	TTCD using EORTC Quality-of-Life Questionnaire Lung Cancer Module (QLQ-LC13) is an initial 10-point increase in symptom score 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-LC13 consists of 13 lung cancer specific items and includes 11 disease-specific scales/items (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication). Each item is scored on a 4-point scale of 1=Not at all to 4=Very much. Scores will be linearly transformed to a score range of 0 to 100. Higher score indicates worsening of symptoms.	Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
Secondary	Percentage of Participants With Adverse Events (AEs) (Phase 2 and Phase 3)		Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
Secondary	Participants' Response to Side Effects of Treatment as Assessed by EORTC IL46 (Phase 2 and Phase 3)	EORTC Item List 46 (IL46) is a validated single-item question that assesses overall side effect impact. Each item is scored on a 4-point scale of 1=Not at all to 4=Very much. Scores will be linearly transformed to a score range of 0 to 100. Higher score indicates a worse outcome.	Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
Secondary	Serum Concentration of Tiragolumab (Phase 2 and Phase 3)		Cycle 1 (each cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at treatment discontinuation (TD) visit (up to approximately 5 years [Phase 2]; up to approximately 7 years [Phase 3])
Secondary	Serum Concentration of Atezolizumab (Phase 2 and Phase 3)		Cycle 1 (each cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at TD visit (up to approximately 5 years [Phase 2]; up to approximately 7 years [Phase 3])
Secondary	Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab (Phase 2 and Phase 3)		Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to approximately 5 years [Phase 2]; up to approximately 7 years [Phase 3])
Secondary	Percentage of Participants With ADAs to Atezolizumab (Phase 2 and Phase 3)		Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to approximately 5 years [Phase 2]; up to approximately 7 years [Phase 3])