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 (SKYSCRAPER-06)

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

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).

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Tiragolumab; Drug: Atezolizumab; Drug: Tiragolumab Matching Placebo; Drug: Pemetrexed; Drug: Carboplatin; Drug: Cisplatin; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 542
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • AZORG Campus Aalst-Moorselbaan
  • Brussels, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Mont-godinne, Belgium, 5530
    • CHU UCL Mont-Godinne
  • Sint-Niklaas, Belgium, 9100
    • Vitaz
• Brazil
  • Ceará
    • Fortaleza, Ceará, Brazil, 60336-550
      • Crio - Centro Regional Integrado de Oncologia
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30360-680
      • Oncocentro Belo Horizonte
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil, 98700-000
      • Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital das Clinicas - UFRGS
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Hospital de Cancer de Barretos
    • São Paulo, São Paulo, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa
    • Sault Ste. Marie, Ontario, Canada, P6B 0A8
      • Sault Area Hospital
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Changchun, China, 132013
    • Jilin Cancer Hospital
  • Changsha, China, 410008
    • Xiangya Hospital Central South University
  • Chengde, China, 067020
    • Affiliated Hospital of Chengde Medical University
  • Chengdu, China, 610041
    • Sichuan Cancer Hospital
  • Chengdu, China, 610047
    • West China Hospital - Sichuan University
  • Hefei, China, 230088
    • Anhui Provincial Hospital
  • Jinan, China, 250013
    • Jinan Central Hospital
  • Pingxiang, China, 337000
    • Pingxiang People's Hospital
  • Qingdao, China, 266042
    • Qingdao Central Hospital
  • Weifang, China, 261041
    • Weifang People's Hospital
  • Wuhan, China, 430079
    • Hubei Cancer Hospital
  • Xi'an, China, 710061
    • The First Affiliated Hospital of Xian Jiao Tong University
  • Xinxiang, China, 453000
    • The First Affiliated Hospital of Xinxiang Medical University
  • Zhengzhou, China, 450052
    • The first affiliated hospital of Zhengzhou university
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet
  • Odense C, Denmark, 5000
    • Odense Universitetshospital, Onkologisk Afdeling R
  • Roskilde, Denmark, 4000
    • Sjællands Universitetshospital, Roskilde
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Marseille, France, 13915
    • Hopital Nord
  • Rennes, France, 35033
    • Hopital de Pontchaillou
  • Strasbourg, France, 67091
    • CHU Strasbourg - Nouvel Hopital Civil
  • Toulouse, France, 31100
    • CHU de Toulouse - Hôpital Larrey
• Germany
  • Berlin, Germany, 14165
    • Helios Klinikum Emil von Behring GmbH
  • Chemnitz, Germany, 09116
    • Klinikum Chemnitz gGmbH
  • Karlsruhe, Germany, 76137
    • St. Vincentius Kliniken Karlsruhe
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie
  • Marburg, Germany, 35032
    • Klinikum der Philipps-Universität Marburg
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Tuen Mun Hospital
  • Hong Kong, Hong Kong
    • Hong Kong United Oncology Centre
  • Shatin, Hong Kong
    • Prince of Wales Hospital
• Italy
  • Friuli Venezia Giulia
    • Aviano, Friuli Venezia Giulia, Italy, 33081
      • Centro Di Riferimento Oncologico
  • Liguria
    • Genoa, Liguria, Italy, 16149
      • A.O. Villa Scassi
  • Tuscany
    • Florence, Tuscany, Italy, 50139
      • Azienda Ospedaliero-Universitaria Careggi
• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Fukuoka, Japan, 830-0011
    • Kurume University Hospital
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Hyōgo, Japan, 665-0827
    • Takarazuka City Hospital
  • Kyoto, Japan, 602-8566
    • University Hospital Kyoto Prefectural University of Medicine
  • Miyagi, Japan, 981-0914
    • Sendai Kousei Hospital
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Osaka, Japan, 573-1191
    • Kansai Medical University Hospital
  • Osaka, Japan, 591-8555
    • NHO Kinki Chuo Chest Medical Center
  • Saitama, Japan, 362-0806
    • Saitama Cancer Center
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR
  • Wakayama, Japan, 641-8510
    • Wakayama Medical University Hospital
• Mexico
  • Mexico City, Mexico, 06700
    • ARKE Estudios Clínicos S.A. de C.V.
  • Querétaro
    • Querétaro City, Querétaro, Mexico, 76000
      • Cuidados Oncologicos
  • San Luis Potosí
    • San Luis Potosí City, San Luis Potosí, Mexico, 78209
      • Oncologico Potosino
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital, Cancer and Blood Research
  • Hamilton, New Zealand, 3204
    • Waikato Hospital - Cancer and Blood Research Trials Unit
  • Palmerston North, New Zealand, 4442
    • Palmerston North Hospital
• Poland
  • Lódz, Poland, 90-338
    • Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna
  • Olsztyn, Poland, 10-357
    • Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
• South Korea
  • Busan, South Korea, 49267
    • Kosin University Gospel Hospital
  • Daegu, South Korea, 41404
    • Kyungpook National University Chilgok Hospital
  • Daejeon, South Korea, 35015
    • Chungnam national university hospital
  • Gyeonggi-do, South Korea, 16247
    • St. Vincent's Hospital
  • Gyeongsangnam-do, South Korea, 51353
    • Samsung Changwon Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03181
    • Kangbuk Samsung Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06591
    • Seoul St Mary's Hospital
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña (CHUAC)
  • Barcelona, Spain, 08003
    • Hospital Del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona
  • Lugo, Spain, 27003
    • Hospital Lucus Augusti
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Seville, Spain, 41014
    • Hospital Univ. Nuestra Señora de Valme
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Balearic Islands
    • Palma de Mallorca, Balearic Islands, Spain, 07198
      • Hospital Son Llàtzer
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • ICO L'Hospitalet
  • LAS Palmas
    • Las Palmas de Gran Canaria, LAS Palmas, Spain, 35016
      • Complejo Hospitalario Universitario Insular?Materno Infantil
• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau
  • Chur, Switzerland, 7000
    • Kantonsspital Graubünden Medizin Onkologie
  • Zurich, Switzerland, 8091
    • Universitatsspital Zurich
• Taiwan
  • Chang-hua, Taiwan, 500
    • Changhua Christian Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital
  • Bangkok, Thailand, 10300
    • Vajira Hospital
  • Bangkok, Thailand, 10700
    • Faculty of Med. Siriraj Hosp.
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01220
    • Adana Baskent University Medical Faculty
  • Ankara, Turkey (Türkiye), 06490
    • Ankara Bilkent City Hospital
  • Ankara, Turkey (Türkiye), 06680
    • Liv Hospital Ankara
  • Diyarbakır, Turkey (Türkiye), 21280
    • Dicle University Faculty of Medicine
  • Edirne, Turkey (Türkiye), 22030
    • Trakya University Medical Faculty
  • Istanbul, Turkey (Türkiye), 34000
    • Istanbul University Cerrahpasa Medical Faculty
  • Kadiköy, Turkey (Türkiye), 34722
    • Medeniyet University Goztepe Training and Research Hospital.
• United Kingdom
  • Hull, United Kingdom, HU16 5JQ
    • Castle Hill Hospital
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • London, United Kingdom, EC1A 7BE
    • Barts & London School of Med
  • Manchester, United Kingdom, M2O 4BX
    • Christie Hospital NHS Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • Whittier, California, United States, 90602
      • PIH Health Whittier Hospital
  • Florida
    • Fort Myers, Florida, United States, 33901
      • SCRI Florida Cancer Specialists South
    • St. Petersburg, Florida, United States, 33705
      • SCRI Florida Cancer Specialists North
    • Winter Park, Florida, United States, 32789
      • Advent Health Orlando
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers PC - Marietta
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology, Inc
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Tennessee Oncology Chattanooga
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute / Tennessee Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin; Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle.	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.; Other Names: MTIG7192A; Drug: Atezolizumab; Atezolizumab at a fixed dose of 1200 mg, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.; Other Names: Tecentriq; Drug: Pemetrexed; Pemetrexed 500 milligrams per square meter (mg/m^2), administered by IV infusion, Q3W on Day 1 of each 21-day cycle.; Drug: 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.; Drug: Cisplatin; Cisplatin 75 mg/m^2, administered by IV infusion, Q3W on Day 1 of each 21-day cycle for 4 cycles.
Placebo Comparator: Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin; Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle.	Drug: Tiragolumab Matching Placebo; Matching placebo, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.; Drug: Pemetrexed; Pemetrexed 500 milligrams per square meter (mg/m^2), administered by IV infusion, Q3W on Day 1 of each 21-day cycle.; Drug: 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.; Drug: Cisplatin; Cisplatin 75 mg/m^2, administered by IV infusion, Q3W on Day 1 of each 21-day cycle for 4 cycles.; Drug: Pembrolizumab; Pembrolizumab at a fixed dose of 200 mg, administered by IV infusion, Q3W, on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) as Determined by the Investigator	PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions. Kaplan-Meier (KM) methodology was used to estimate the median PFS.	From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)
Overall Survival (OS)	OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS.	From randomization to death from any cause (up to approximately 40 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS as Determined by the Independent Review Facility (IRF)	PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1 criteria, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions. KM methodology was used to estimate the median PFS.	From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)
Investigator Assessed PFS in Participants With PD-L1 Expression at TPS/TC >=1%	PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1 criteria, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions. KM methodology was used to estimate the median PFS.	From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)
Investigator Assessed PFS in Participants With PD-L1 Expression at TPS/TC >=50%	PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions. KM methodology was used to estimate the median PFS.	From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)
OS in Participants With PD-L1 Expression at TPS/TC >=1%	OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS.	From randomization to death from any cause (up to approximately 40 months)
OS in Participants With PD-L1 Expression at TPS/TC >= 50%	OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS.	From randomization to death from any cause (up to approximately 40 months)
PFS Rate at Month 6 and Month 12	PFS at 6 months and 12 months was defined as the percentage of participants who have not experienced PD as determined by the investigator according to RECIST v1.1 or death from any cause at 6 months and at 12 months, respectively. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions.	At Month 6 and Month 12
OS Rate at Month 12 and Month 24	OS rate at 12 months and 24 months was defined as the percentage of participants who have not experienced death from any cause at 12 and 24 months, respectively.	At Month 12 and Month 24
Duration of Response (DOR)	DOR was defined as the time from the first occurrence of a documented objective response (OR) to PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. Complete response (CR) was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Partial response (PR) was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm. KM methodology was used to estimate the median DOR.	Up to approximately 40 months
Objective Response Rate (ORR)	ORR was defined as a percentage of participants with a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.	Up to approximately 40 months
Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning (PF) as Measured by European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC-QLQ-C30)	EORTC QLQ-C30=self-reported measure, with 30 questions assessing 5 aspects of subjects functioning (physical, emotional, role, cognitive & social), 3 symptom scales (fatigue, nausea & vomiting, & pain), global health status (GHS) & Quality of Life (QoL), & 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties) within the previous week. Functioning & symptoms items were scored on a 4-point scale: 1=not at all to 4=very much. Scores were linearly transformed to a range of 0 to 100, with higher scores reflecting better functioning. TTCD was defined time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration was defined as score decrease of ≥10 from baseline in PF scale score that were held for at least two consecutive assessments or an initial ≥10 decrease from baseline followed by death from any cause within 3 weeks.	Up to approximately 40 months
TTCD in Participant-Reported Global Health Status (GHS)/Quality of Life (QoL) as Measured by EORTC QLQ-C30	EORTC QLQ-C30=self-reported measure, with 30 questions assessing 5 aspects of subjects functioning (physical, emotional, role, cognitive & social), 3 symptom scales (fatigue, nausea & vomiting, & pain), global health status (GHS) & Quality of Life (QoL), & 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties) within the previous week . GHS and QoL items were scored on a 7-point scale (1=very poor 7=excellent). Scores were linearly transformed to a range of 0 to 100, with higher scores reflecting better GHS/QoL. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration was defined as score decrease of ≥10 from baseline in GHS/QoL scale score that were held for at least two consecutive assessments or an initial ≥10 decrease from baseline followed by death from any cause within 3 weeks.	Up to approximately 40 months
TTCD in Participant-Reported Dyspnoea as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13)	The EORTC QLQ-LC13 is comprised 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). Symptoms were scored on a 4-point scale: 1=not at all to 4=very much. Scores are linearly transformed to a range of 0 to 100. A higher score indicates a worse level of dyspnoea. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration in symptoms was defined as a score increase of ≥ 10-point from baseline in a symptom score that must be held for at least two consecutive assessments or an initial increase ≥ 10-point from baseline followed by death from any cause within 3 weeks.	Up to approximately 40 months
TTCD in Participant-Reported Chest Pain, as Measured by EORTC QLQ-LC13	The EORTC QLQ-LC13 is comprised 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). Chest pain were scored on a 4-point scale: 1=not at all to 4=very much. Scores are linearly transformed to a range of 0 to 100. A higher score indicates a worse level of chest pain. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration in symptoms was defined as a score increase of ≥ 10-point from baseline in a symptom score that must be held for at least two consecutive assessments or an initial increase ≥ 10-point from baseline followed by death from any cause within 3 weeks.	Up to approximately 40 months
TTCD in Participant-Reported Cough, as Measured by EORTC QLQ-LC13	The EORTC QLQ-LC13 is comprised 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). Cough were scored on a 4-point scale: 1=not at all to 4=very much. Scores are linearly transformed to a range of 0 to 100. A higher score indicates a worse level of cough. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration in symptoms was defined as a score increase of ≥ 10-point from baseline in a symptom score that must be held for at least two consecutive assessments or an initial increase ≥ 10-point from baseline followed by death from any cause within 3 weeks.	Up to approximately 40 months
Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.	From study start up to 90 days after last dose (up to approximately 40.8 months)
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46)	The EORTC IL46 is a validated single-item question that assesses overall side effect impact, i.e. "To what extent have you been troubled with side-effects from your treatment ". Each item is scored on a 4-point scale (1= Not at all, 2= A Little, 3= Quite a Bit, and 4= Very Much).	Baseline, Day 1 of Cycles 2, 3, 4, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57 and treatment discontinuation visit (each cycle=21 days) (Up to 40 months)
Serum Concentration of Atezolizumab		Predose Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 and at treatment completion (TC)/early discontinuation (ED); and 0.5 hour (h) postdose Day 1 of Cycle 1 (each cycle=21 days) (Up to 40 months)
Serum Concentration of Tiragolumab		Predose Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 and at TC/ED; and 0.5 hour (h) postdose Day 1 of Cycle 1 (each cycle=21 days) (Up to 40 months)
Number of Participants With Treatment-Emergent Anti-drug Antibodies (ADAs) to Atezolizumab	Participants who received atezolizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.	Up to approximately 40 months
Number of Participants With Treatment-Emergent ADAs to Tiragolumab	Participants who received tiragolumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following tiragolumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 t.u. greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.	Up to approximately 40 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Socinski MA, Stahel R, Lee DH, Cappuzzo F, Nishio M, Lovly CM, Ozyilkan O, Li Q, Johnson M, Garon EB, Kilickap S, Ferreira da Silva FA, Alatorre-Alexander J, Meng R, Amin R, Matheny C, Troutman S, Wen X, Patil NS, Zou W, Rodriguez-Abreu D. Tiragolumab Plus Atezolizumab and Chemotherapy for Advanced Nonsquamous Non-Small Cell Lung Cancer: The Phase 3 SKYSCRAPER-06 Randomized Clinical Trial. JAMA Oncol. 2026 Apr 30:e260818. doi: 10.1001/jamaoncol.2026.0818. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Actual): April 19, 2024
• Study Completion (Actual): November 20, 2025

Study Registration Dates

• First Submitted: October 30, 2020
• First Submitted That Met QC Criteria: November 5, 2020
• First Posted (Actual): November 6, 2020

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Platinum Compounds; Pemetrexed; Carboplatin; Cisplatin; pembrolizumab; atezolizumab; Tiragolumab
• Other Study ID Numbers: BO42592; 2020-002851-39 (EudraCT Number); 2022-502031-20-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No