Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202301834998443 Date of Approval: 23/01/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
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 (SKYSCRAPER-06)
Official 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
Brief summary describing the background and objectives of the trial Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all cases of lung cancer (Molina et al. 2008; Howlader et al. 2015). Non-small-cell lung cancer can be divided into 2 subcategories: squamous and non-squamous. Squamous cell histology accounts for approximately 25% of NSCLC (Langer et al. 2010). Non-squamous NSCLC includes several histological subtypes, the most common of which is adenocarcinoma, which accounts for more than half of all NSCLC. The remaining cases of NSCLC are represented by other non-squamous NSCLC histologies, including large cell carcinoma, neuroendocrine tumors, sarcomatoid carcinoma, and poorly differentiated histology. 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).
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SKY 06
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 03/04/2023
Actual trial start date
Anticipated date of last follow up 14/05/2027
Actual Last follow-up date
Anticipated target sample size (number of participants) 540
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL https://clinicaltrials.gov/ct2/show/NCT04619797
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Tiragolumab plus Atezolizumab plus Pemetrexed plus Carboplatin or Cisplatin 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 Name: 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 Name: 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. 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 Name: 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 Name: 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. 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. 270
Control Group Placebo plus Pembrolizumab plus Pemetrexed plus Carboplatin or Cisplatin 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: Tiragolumab Matching Placebo Matching placebo, administered by IV infusion, Q3W on Day 1 of each 21-day cycle. Drug: Pembrolizumab Pembrolizumab at a fixed dose of 200 mg, 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: Tiragolumab Matching Placebo Matching placebo, administered by IV infusion, Q3W on Day 1 of each 21-day cycle. Drug: Pembrolizumab Pembrolizumab at a fixed dose of 200 mg, administered by IV infusion, Q3W, on Day 1 of each 21-day cycle. 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. 270 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
-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. -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. 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/12/2022 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
OFF MBAGATHI ROAD, NAIROBI, KENYA Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 10/03/2023 KNH UON ERC
Ethics Committee Address
Street address City Postal code Country
Nairobi Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome -Investigator-Assessed Confirmed Objective Response Rate (ORR) (Phase 2) [ Time Frame: Up to approximately 5 years ] -Investigator-Assessed Progression-Free Survival (PFS) (Phase 2 and Phase 3) [ Time Frame: 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]) ] -Overall Survival (Phase 3) [ Time Frame: From randomization to death from any cause (up to approximately 7 years) ] See timepoints listed above
Secondary Outcome -Overall Survival (Phase 2) [ Time Frame: From randomization to death from any cause (up to approximately 5 years) ] -PFS as Determined by an Independent Review Facility (IRF) (Phase 3) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 7 years) ] -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) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 7 years) ] -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) [ Time Frame: From randomization to death from any cause (up to approximately 7 years) ] -Investigator-Assessed PFS at 6 Months and 12 Months (Phase 3) [ Time Frame: 6 months, 12 months ] -OS Rate at 12 Months and 24 Months (Phase 3) [ Time Frame: 12 months, 24 months ] Timepoints listed above
Secondary Outcome -Investigator-Assessed Confirmed ORR (Phase 3) [ Time Frame: Up to approximately 7 years ] -Investigator-Assessed Duration of Response (DOR) (Phase 2 and Phase 3) [ Time Frame: 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]) ] -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) [ Time Frame: Up to approximately 5 years (Phase 2); up to approximately 7 years (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. Timepoints listed above
Secondary Outcome -TTCD in Participant-Reported Lung Cancer Symptoms for Cough, Dyspnea, and Chest Pain, as Measured by EORTC QLQ-LC13 (Phase 2 and Phase 3) [ Time Frame: Up to approximately 5 years (Phase 2); up to approximately 7 years (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. -Percentage of Participants With Adverse Events (AEs) (Phase 2 and Phase 3) [ Time Frame: Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3) ] -Participants' Response to Side Effects of Treatment as Assessed by EORTC IL46 (Phase 2 and Phase 3) [ Time Frame: Up to approximately 5 years (Phase 2); up to approximately 7 years (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. Timepoints listed above
Secondary Outcome -Serum Concentration of Tiragolumab (Phase 2 and Phase 3) [ Time Frame: 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]) ] -Serum Concentration of Atezolizumab (Phase 2 and Phase 3) [ Time Frame: 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]) ] -Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab (Phase 2 and Phase 3) [ Time Frame: 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]) ] -Percentage of Participants With ADAs to Atezolizumab (Phase 2 and Phase 3) [ Time Frame: 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]) ] Timepoints listed above
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
International Cancer Institute Nandi Road 8/10, Eldoret, Kenya, 8088-30100 Eldoret 30100 Kenya
UNIVERSITY OF NAIROBI INSTITUTE OF TROPICAL AND INFECTIOUS DISEASES UNITID P.O.BOX 19676 00200 NAIROBI Nairobi 00200 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Hoffmann La Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi 00100 Kenya
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Hoffmann La Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi 00100 Kenya Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Fredrick Asirwa director@intercancer.com +254700522149 International Cancer Institute, Nandi Road 8/10, Eldoret, Kenya, 8088-30100
City Postal code Country Position/Affiliation
Eldoret 30100 Kenya Professor of Hematology and Oncology
Role Name Email Phone Street address
Scientific Enquiries Isabelle Rooney rooney.isabelle@gene.com +16504678265 South San Francisco Building 40 Room 40 N5 3
City Postal code Country Position/Affiliation
South San Francisco United States of America MEDICAL MONITOR
Role Name Email Phone Street address
Public Enquiries Nour Ashraf nour.ashraf@roche.com +201003300246 Cairo Festival City Plot 14b01 Building A2 4th Floor
City Postal code Country Position/Affiliation
Cairo 11835 Egypt Clinical Operations Lead
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Plan description: -Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). Clinical Study Report Roche commits to submit a manuscript to a peer-reviewed journal reporting primary clinical trials results no later than 18 months after the first product approval or decision to discontinue development of the product. Available studies are listed and available on the Vivli platform. Data requestors should use the Vivli data request form to request companies data Package(s). If approved requestors will need to sign a Data Use Agreement and the anonymized data will be shared in the Vivli secure research environment.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://vivli.org/ourmember/roche/ No
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