Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04619797




Registration number
NCT04619797
Ethics application status
Date submitted
30/10/2020
Date registered
6/11/2020
Date last updated
5/06/2025

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2020-002851-39
Secondary ID [2] 0 0
BO42592
Universal Trial Number (UTN)
Trial acronym
SKYSCRAPER-06
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer (NSCLC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tiragolumab
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Drugs - Tiragolumab Matching Placebo
Treatment: Drugs - Pembrolizumab

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: Atezolizumab
Atezolizumab at a fixed dose of 1200 mg, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

Treatment: Drugs: Pemetrexed
Pemetrexed 500 milligrams per square meter (mg/m\^2), administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

Treatment: Drugs: 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.

Treatment: Drugs: Cisplatin
Cisplatin 75 mg/m\^2, administered by IV infusion, Q3W on Day 1 of each 21-day cycle for 4 cycles.

Treatment: Drugs: Tiragolumab Matching Placebo
Matching placebo, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

Treatment: Drugs: Pembrolizumab
Pembrolizumab at a fixed dose of 200 mg, administered by IV infusion, Q3W, on Day 1 of each 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Investigator-Assessed Confirmed Objective Response Rate (ORR) (Phase 2)
Assessment method [1] 0 0
Timepoint [1] 0 0
Up to approximately 5 years
Primary outcome [2] 0 0
Investigator-Assessed Progression-Free Survival (PFS) (Phase 2 and Phase 3)
Assessment method [2] 0 0
Timepoint [2] 0 0
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 outcome [3] 0 0
Overall Survival (Phase 3)
Assessment method [3] 0 0
Timepoint [3] 0 0
From randomization to death from any cause (up to approximately 7 years)
Secondary outcome [1] 0 0
Overall Survival (Phase 2)
Assessment method [1] 0 0
Timepoint [1] 0 0
From randomization to death from any cause (up to approximately 5 years)
Secondary outcome [2] 0 0
PFS as Determined by an Independent Review Facility (IRF) (Phase 3)
Assessment method [2] 0 0
Timepoint [2] 0 0
From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 7 years)
Secondary outcome [3] 0 0
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)
Assessment method [3] 0 0
Timepoint [3] 0 0
From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 7 years)
Secondary outcome [4] 0 0
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)
Assessment method [4] 0 0
Timepoint [4] 0 0
From randomization to death from any cause (up to approximately 7 years)
Secondary outcome [5] 0 0
Investigator-Assessed PFS at 6 Months and 12 Months (Phase 3)
Assessment method [5] 0 0
Timepoint [5] 0 0
6 months, 12 months
Secondary outcome [6] 0 0
OS Rate at 12 Months and 24 Months (Phase 3)
Assessment method [6] 0 0
Timepoint [6] 0 0
12 months, 24 months
Secondary outcome [7] 0 0
Investigator-Assessed Confirmed ORR (Phase 3)
Assessment method [7] 0 0
Timepoint [7] 0 0
Up to approximately 7 years
Secondary outcome [8] 0 0
Investigator-Assessed Duration of Response (DOR) (Phase 2 and Phase 3)
Assessment method [8] 0 0
Timepoint [8] 0 0
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 outcome [9] 0 0
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)
Assessment method [9] 0 0
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.
Timepoint [9] 0 0
Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
Secondary outcome [10] 0 0
TTCD in Participant-Reported Lung Cancer Symptoms for Cough, Dyspnea, and Chest Pain, as Measured by EORTC QLQ-LC13 (Phase 2 and Phase 3)
Assessment method [10] 0 0
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.
Timepoint [10] 0 0
Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
Secondary outcome [11] 0 0
Percentage of Participants With Adverse Events (AEs) (Phase 2 and Phase 3)
Assessment method [11] 0 0
Timepoint [11] 0 0
Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
Secondary outcome [12] 0 0
Participants' Response to Side Effects of Treatment as Assessed by EORTC IL46 (Phase 2 and Phase 3)
Assessment method [12] 0 0
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.
Timepoint [12] 0 0
Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3)
Secondary outcome [13] 0 0
Serum Concentration of Tiragolumab (Phase 2 and Phase 3)
Assessment method [13] 0 0
Timepoint [13] 0 0
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 outcome [14] 0 0
Serum Concentration of Atezolizumab (Phase 2 and Phase 3)
Assessment method [14] 0 0
Timepoint [14] 0 0
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 outcome [15] 0 0
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab (Phase 2 and Phase 3)
Assessment method [15] 0 0
Timepoint [15] 0 0
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 outcome [16] 0 0
Percentage of Participants With ADAs to Atezolizumab (Phase 2 and Phase 3)
Assessment method [16] 0 0
Timepoint [16] 0 0
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])

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2025
Actual
Sample size
Target
Accrual to date
Final
542
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
Belgium
State/province [8] 0 0
Aalst
Country [9] 0 0
Belgium
State/province [9] 0 0
Bruxelles
Country [10] 0 0
Belgium
State/province [10] 0 0
Mont-godinne
Country [11] 0 0
Belgium
State/province [11] 0 0
Sint Niklaas
Country [12] 0 0
Brazil
State/province [12] 0 0
Ceará
Country [13] 0 0
Brazil
State/province [13] 0 0
Minas Gerais
Country [14] 0 0
Brazil
State/province [14] 0 0
Rio Grande Do Sul
Country [15] 0 0
Brazil
State/province [15] 0 0
São Paulo
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
China
State/province [18] 0 0
Beijing
Country [19] 0 0
China
State/province [19] 0 0
Changchun
Country [20] 0 0
China
State/province [20] 0 0
Changsha City
Country [21] 0 0
China
State/province [21] 0 0
Changzhou
Country [22] 0 0
China
State/province [22] 0 0
Chengde City
Country [23] 0 0
China
State/province [23] 0 0
Chengdu City
Country [24] 0 0
China
State/province [24] 0 0
Hefei
Country [25] 0 0
China
State/province [25] 0 0
Jinan City
Country [26] 0 0
China
State/province [26] 0 0
Pingxiang City
Country [27] 0 0
China
State/province [27] 0 0
Qingdao City
Country [28] 0 0
China
State/province [28] 0 0
Weifang City
Country [29] 0 0
China
State/province [29] 0 0
Wuhan
Country [30] 0 0
China
State/province [30] 0 0
Xi'an City
Country [31] 0 0
China
State/province [31] 0 0
Xinxiang City
Country [32] 0 0
China
State/province [32] 0 0
Zhengzhou
Country [33] 0 0
Denmark
State/province [33] 0 0
København Ø
Country [34] 0 0
Denmark
State/province [34] 0 0
Odense C
Country [35] 0 0
Denmark
State/province [35] 0 0
Roskilde
Country [36] 0 0
France
State/province [36] 0 0
Bordeaux
Country [37] 0 0
France
State/province [37] 0 0
Marseille cedex 20
Country [38] 0 0
France
State/province [38] 0 0
Rennes
Country [39] 0 0
France
State/province [39] 0 0
Strasbourg
Country [40] 0 0
France
State/province [40] 0 0
Toulouse cedex 9
Country [41] 0 0
Germany
State/province [41] 0 0
Berlin
Country [42] 0 0
Germany
State/province [42] 0 0
Chemnitz
Country [43] 0 0
Germany
State/province [43] 0 0
Karlsruhe
Country [44] 0 0
Germany
State/province [44] 0 0
Mainz
Country [45] 0 0
Germany
State/province [45] 0 0
Marburg
Country [46] 0 0
Hong Kong
State/province [46] 0 0
Hong Kong
Country [47] 0 0
Hong Kong
State/province [47] 0 0
Shatin
Country [48] 0 0
Italy
State/province [48] 0 0
Friuli-Venezia Giulia
Country [49] 0 0
Italy
State/province [49] 0 0
Liguria
Country [50] 0 0
Italy
State/province [50] 0 0
Toscana
Country [51] 0 0
Japan
State/province [51] 0 0
Fukuoka
Country [52] 0 0
Japan
State/province [52] 0 0
Hiroshima
Country [53] 0 0
Japan
State/province [53] 0 0
Hyogo
Country [54] 0 0
Japan
State/province [54] 0 0
Kyoto
Country [55] 0 0
Japan
State/province [55] 0 0
Miyagi
Country [56] 0 0
Japan
State/province [56] 0 0
Osaka
Country [57] 0 0
Japan
State/province [57] 0 0
Saitama
Country [58] 0 0
Japan
State/province [58] 0 0
Tokyo
Country [59] 0 0
Japan
State/province [59] 0 0
Wakayama
Country [60] 0 0
Korea, Republic of
State/province [60] 0 0
Busan
Country [61] 0 0
Korea, Republic of
State/province [61] 0 0
Daejeon
Country [62] 0 0
Korea, Republic of
State/province [62] 0 0
Gyeonggi-do
Country [63] 0 0
Korea, Republic of
State/province [63] 0 0
Gyeongsangnam-do
Country [64] 0 0
Korea, Republic of
State/province [64] 0 0
Seoul
Country [65] 0 0
Mexico
State/province [65] 0 0
Mexico CITY (federal District)
Country [66] 0 0
Mexico
State/province [66] 0 0
Queretaro
Country [67] 0 0
Mexico
State/province [67] 0 0
Ciudad de México
Country [68] 0 0
New Zealand
State/province [68] 0 0
Auckland
Country [69] 0 0
New Zealand
State/province [69] 0 0
Hamilton
Country [70] 0 0
New Zealand
State/province [70] 0 0
Palmerston North
Country [71] 0 0
New Zealand
State/province [71] 0 0
Tauranga
Country [72] 0 0
Poland
State/province [72] 0 0
Lodz
Country [73] 0 0
Poland
State/province [73] 0 0
Olsztyn
Country [74] 0 0
Spain
State/province [74] 0 0
Barcelona
Country [75] 0 0
Spain
State/province [75] 0 0
Islas Baleares
Country [76] 0 0
Spain
State/province [76] 0 0
LAS Palmas
Country [77] 0 0
Spain
State/province [77] 0 0
La Coruna
Country [78] 0 0
Spain
State/province [78] 0 0
Lugo
Country [79] 0 0
Spain
State/province [79] 0 0
Madrid
Country [80] 0 0
Spain
State/province [80] 0 0
Sevilla
Country [81] 0 0
Spain
State/province [81] 0 0
Valencia
Country [82] 0 0
Switzerland
State/province [82] 0 0
Aarau
Country [83] 0 0
Switzerland
State/province [83] 0 0
Chur
Country [84] 0 0
Switzerland
State/province [84] 0 0
Zürich
Country [85] 0 0
Taiwan
State/province [85] 0 0
Chang Hua
Country [86] 0 0
Taiwan
State/province [86] 0 0
Taichung
Country [87] 0 0
Taiwan
State/province [87] 0 0
Taipei City
Country [88] 0 0
Thailand
State/province [88] 0 0
Bangkok
Country [89] 0 0
Thailand
State/province [89] 0 0
ChiangMai
Country [90] 0 0
Thailand
State/province [90] 0 0
Songkhla
Country [91] 0 0
Turkey
State/province [91] 0 0
Ankara
Country [92] 0 0
Turkey
State/province [92] 0 0
Diyarbakir
Country [93] 0 0
Turkey
State/province [93] 0 0
Istanbul
Country [94] 0 0
Turkey
State/province [94] 0 0
Kadiköy
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Hull
Country [96] 0 0
United Kingdom
State/province [96] 0 0
London
Country [97] 0 0
United Kingdom
State/province [97] 0 0
Manchester
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04619797