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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)

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ClinicalTrials.gov Identifier: NCT04619797
Recruitment Status : Recruiting
First Posted : November 6, 2020
Last Update Posted : January 19, 2023
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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).


Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer (NSCLC) Drug: Tiragolumab Drug: Atezolizumab Drug: Pemetrexed Drug: Carboplatin Drug: Cisplatin Drug: Tiragolumab Matching Placebo Drug: Pembrolizumab Phase 2 Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 540 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 14, 2020
Estimated Primary Completion Date : May 14, 2024
Estimated Study Completion Date : May 14, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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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 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.
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: 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.


Outcome Measures
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Primary Outcome Measures :
  1. Investigator-Assessed Confirmed Objective Response Rate (ORR) (Phase 2) [ Time Frame: Up to approximately 5 years ]
  2. 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]) ]
  3. Overall Survival (Phase 3) [ Time Frame: From randomization to death from any cause (up to approximately 7 years) ]

Secondary Outcome Measures :
  1. Overall Survival (Phase 2) [ Time Frame: From randomization to death from any cause (up to approximately 5 years) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. Investigator-Assessed PFS at 6 Months and 12 Months (Phase 3) [ Time Frame: 6 months, 12 months ]
  6. OS Rate at 12 Months and 24 Months (Phase 3) [ Time Frame: 12 months, 24 months ]
  7. Investigator-Assessed Confirmed ORR (Phase 3) [ Time Frame: Up to approximately 7 years ]
  8. 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]) ]
  9. 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.

  10. 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.

  11. 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) ]
  12. 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.

  13. 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]) ]
  14. 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]) ]
  15. 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]) ]
  16. 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]) ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04619797


Contacts
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Contact: Reference Study ID Number: BO42592 https://forpatients.roche.com/ 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04619797    
Other Study ID Numbers: BO42592
2020-002851-39 ( EudraCT Number )
First Posted: November 6, 2020    Key Record Dates
Last Update Posted: January 19, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data 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 the Sharing of Clinical 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).
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cisplatin
 Carboplatin
Pembrolizumab
Pemetrexed
Atezolizumab
Antineoplastic Agents
Antineoplastic Agents, Immunological
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors