E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-small cell lung cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
Non-small cell lung cancer is cancer of the lung which is not of the small cell carcinoma (oat cell carcinoma) type. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10079440 |
E.1.2 | Term | Non-squamous non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the efficacy 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) on the basis of confirmed objective response rate (ORR) and progression-free survival (PFS), as assessed by investigators according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy 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) on the basis of overall survival, duration of response and time to confirmed deterioration in patient-reported physical functioning and global health status/quality of life (GHS/QoL), and in patient-reported lung cancer symptoms for cough, dyspnea (a multi-item subscale), and chest pain
• To evaluate the safety 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)
• To characterize the pharmacokinetics of tiragolumab and atezolizumab
• To evaluate the immune response to tiragolumab and atezolizumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
• No prior systemic treatment for metastatic non-squamous NSCLC
• Known tumor PD-L1 status
• Measurable disease, as defined by RECIST v1.1
• Life expectancy >= 12 weeks
• Adequate hematologic and end-organ function
• Negative HIV test at screening
• Serology test negative for active hepatitis B virus or active hepatitis C virus at screening |
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E.4 | Principal exclusion criteria |
• Patients with NSCLC which harbors a mutation in the EGFR gene or an ALK fusion oncogene
• 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 peumonitis
• 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
• 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Investigator-Assessed Confirmed Objective Response Rate (ORR)
2. Investigator-Assessed Progression-free survival (PFS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Overall survival
2. Duration of response for patients with a confirmed objective response, defined as the time from first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first)
3. Time to confirmed deterioration (TTCD) in patient-reported physical functioning and global health status/quality of life (GHS/QoL), as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core (QLQ-C30), and in patient-reported lung cancer symptoms for cough, dyspnea (a multi-item subscale), and chest pain, as measured through the use of the EORTC Quality-of-Life Questionnaire Lung Cancer Module (QLQ-LC13)
4. Percentage of Participants with Adverse Events (AEs)
5. Frequency of patients’ response of the degree they are troubled with treatment symptoms, as assessed through use of the single-item EORTC IL46
6. Serum concentrations of tiragolumab and atezolizumab
7. Percentage of participants with anti-drug antibodies (ADAs) to tiragolumab
8. Percentage of participants with ADAs to atezolizumab. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5. Up to 5 years
6-8. Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16 and at treatment discontinuation (up to 5 years). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Germany |
Hong Kong |
Italy |
Korea, Republic of |
New Zealand |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of this study will occur when the last data required for all study analyses are collected.
In addition, the Sponsor may decide to terminate the study at any time. If the Sponsor decides to terminate the study, patients who are still receiving study treatment or undergoing survival follow-up may be enrolled in an extension study and/or offered continued access to study treatment through a post-trial access program. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |