Clinical trial NCT04619797: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Non-small Cell Lung Cancer (NSCLC)
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-11-06
Enrollment: 542
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: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Investigator-Assessed Confirmed Objective Response Rate (ORR) (Phase 2)
timeFrame: Up to approximately 5 years
measure: Investigator-Assessed Progression-Free Survival (PFS) (Phase 2 and Phase 3)
timeFrame: 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])
measure: Overall Survival (Phase 3)
timeFrame: From randomization to death from any cause (up to approximately 7 years)
Secondary outcomes:
measure: Overall Survival (Phase 2)
timeFrame: From randomization to death from any cause (up to approximately 5 years)
measure: PFS as Determined by an Independent Review Facility (IRF) (Phase 3)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 7 years)
measure: 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)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 7 years)
measure: 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)
timeFrame: From randomization to death from any cause (up to approximately 7 years)
measure: Investigator-Assessed PFS at 6 Months and 12 Months (Phase 3)
timeFrame: 6 months, 12 months
measure: OS Rate at 12 Months and 24 Months (Phase 3)
timeFrame: 12 months, 24 months
measure: Investigator-Assessed Confirmed ORR (Phase 3)
timeFrame: Up to approximately 7 years
measure: Investigator-Assessed Duration of Response (DOR) (Phase 2 and Phase 3)
timeFrame: 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])
measure: 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)
timeFrame: Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
measure: TTCD in Participant-Reported Lung Cancer Symptoms for Cough, Dyspnea, and Chest Pain, as Measured by EORTC QLQ-LC13 (Phase 2 and Phase 3)
timeFrame: Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
measure: Percentage of Participants With Adverse Events (AEs) (Phase 2 and Phase 3)
timeFrame: Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
measure: Participants' Response to Side Effects of Treatment as Assessed by EORTC IL46 (Phase 2 and Phase 3)
timeFrame: Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
measure: Serum Concentration of Tiragolumab (Phase 2 and Phase 3)
timeFrame: 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])
measure: Serum Concentration of Atezolizumab (Phase 2 and Phase 3)
timeFrame: 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])
measure: Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab (Phase 2 and Phase 3)
timeFrame: 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])
measure: Percentage of Participants With ADAs to Atezolizumab (Phase 2 and Phase 3)
timeFrame: 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])
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Torrance
country: United States
facility: Torrance Memorial Physician Network/Cancer Care
state: California
city: Whittier
country: United States
facility: PIH Health Whittier Hospital
state: California
city: Fort Myers
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Saint Petersburg
country: United States
facility: SCRI Florida Cancer Specialists North
state: Florida
city: Winter Park
country: United States
facility: Advent Health Orlando
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC - Marietta
state: Georgia
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc
state: Indiana
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Chattanooga
country: United States
facility: Tennessee Oncology Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology
state: Tennessee
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Aalst
country: Belgium
facility: AZORG Campus Aalst-Moorselbaan
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Mont-godinne
country: Belgium
facility: CHU UCL Mont-Godinne
city: Sint Niklaas
country: Belgium
facility: Vitaz
city: Fortaleza
country: Brazil
facility: Crio - Centro Regional Integrado de Oncologia
state: Ceará
city: Belo Horizonte
country: Brazil
facility: Oncocentro Belo Horizonte
state: Minas Gerais
city: Ijui
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: São Paulo
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Sault Ste. Marie
country: Canada
facility: Sault Area Hospital
state: Ontario
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changsha City
country: China
facility: Xiangya Hospital Central South University
city: Changzhou
country: China
facility: Changzhou First People's Hospital
city: Chengde City
country: China
facility: Affiliated Hospital of Chengde Medical University
city: Chengdu City
country: China
facility: Sichuan Cancer Hospital
city: Chengdu City
country: China
facility: West China Hospital - Sichuan University
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Jinan City
country: China
facility: Jinan Central Hospital
city: Pingxiang City
country: China
facility: Pingxiang People Hospital
city: Qingdao City
country: China
facility: Qingdao Central Hospital
city: Weifang City
country: China
facility: Weifang People's Hospital
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Xi'an City
country: China
facility: The First Affiliated Hospital of Xian Jiao Tong University
city: Xinxiang City
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Odense C
country: Denmark
facility: Odense Universitetshospital, Onkologisk Afdeling R
city: Roskilde
country: Denmark
facility: Sjællands Universitetshospital, Roskilde
city: Bordeaux
country: France
facility: Institut Bergonie
city: Marseille cedex 20
country: France
facility: Hopital Nord
city: Rennes
country: France
facility: Hopital de Pontchaillou
city: Strasbourg
country: France
facility: CHU Strasbourg - Nouvel Hopital Civil
city: Toulouse cedex 9
country: France
facility: CHU de Toulouse - Hôpital Larrey
city: Berlin
country: Germany
facility: Helios Klinikum Emil von Behring GmbH
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Karlsruhe
country: Germany
facility: St. Vincentius Kliniken Karlsruhe
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie
city: Marburg
country: Germany
facility: Klinikum der Philipps-Universität Marburg
city: Hong Kong
country: Hong Kong
facility: Hong Kong United Oncology Centre
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico
state: Friuli-Venezia Giulia
city: Genova
country: Italy
facility: A.O. Villa Scassi
state: Liguria
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
state: Toscana
city: Fukuoka
country: Japan
facility: Kurume University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hyogo
country: Japan
facility: Takarazuka City Hospital
city: Kyoto
country: Japan
facility: University Hospital Kyoto Prefectural University of Medicine
city: Miyagi
country: Japan
facility: Sendai Kousei Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Osaka
country: Japan
facility: Kansai Medical University Hospital
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: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: St. Vincent's 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: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: Querétaro
country: Mexico
facility: Cuidados oncologicos
state: Queretaro
city: Ciudad de México
country: Mexico
facility: ARKE Estudios Clínicos S.A. de C.V.
city: Auckland
country: New Zealand
facility: Auckland City Hospital, Cancer and Blood Research
city: Hamilton
country: New Zealand
facility: Waikato Hospital - Cancer and Blood Research Trials Unit
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
city: Tauranga
country: New Zealand
facility: Tauranga Hospital, Clinical Trials Unit
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna
city: Olsztyn
country: Poland
facility: Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
city: L Hospitalet De Llobregat
country: Spain
facility: ICO L'Hospitalet
state: Barcelona
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
state: Islas Baleares
city: Las Palmas de Gran Canaria
country: Spain
facility: Complejo Hospitalario Universitario Insular?Materno Infantil
state: LAS Palmas
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: La Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
city: Lugo
country: Spain
facility: Hospital Lucus Augusti
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Univ. Nuestra Señora de Valme
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden Medizin Onkologie
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
city: Chang Hua
country: Taiwan
facility: Changhua Christian Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.
city: ChiangMai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: Ankara
country: Turkey
facility: Ankara Bilkent City Hospital
city: Ankara
country: Turkey
facility: Liv Hospital Ankara
city: Diyarbakir
country: Turkey
facility: Dicle University Faculty of Medicine
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Kadiköy
country: Turkey
facility: Medeniyet University Goztepe Training and Research Hospital.
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: London
country: United Kingdom
facility: Barts & London School of Med
city: London
country: United Kingdom
facility: Guy'S Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: