E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable Stage III Non-small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Unresectable Stage III Non-small Cell Lung Cancer |
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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 | 10029519 |
E.1.2 | Term | Non-small cell lung cancer stage III |
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 PFS in participants treated with cCRT plus M7824 followed by M7824 or cCRT plus placebo followed by durvalumab |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety in participants treated with cCRT plus M7824 followed by M7824 or cCRT plus placebo followed by durvalumab To evaluate OS in participants treated with cCRT plus M7824 followed by M7824 or cCRT plus placebo followed by durvalumab To evaluate changes in lung function in participants treated with cCRT plus M7824 followed by M7824 or cCRT plus placebo followed by durvalumab To evaluate the association of PD-L1 expression at Baseline with efficacy in participants treated with cCRT plus M7824 followed by M7824 or cCRT plus placebo followed by durvalumab To evaluate objective tumor response in participants treated with cCRT plus M7824 followed by M7824 or cCRT plus placebo followed by durvalumab To evaluate duration of response in participants treated with cCRT plus M7824 followed by M7824 or cCRT plus placebo followed by durvalumab To characterize PK profile of M7824 plus cCRT and after cCRT To characterize the immunogenicity of M7824 plus cCRT and after cCRT |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Investigator Participants must have histologically documented NSCLC who present with Stage III locally advanced, unresectable disease (International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging Manual in Thoracic Oncology], v8).
2. Participants with tumor harboring an EGFR sensitizing (activating) mutation, ALK translocation, ROS-1 rearrangement are eligible. These tests are not required for enrollment in the study.
3. Participants must have adequate pulmonary function defined as a forced expiratory volume in 1 second (FEV1) ≥ 1.2 liters or ≥ 50% of predicted normal volume measured within 3 weeks prior to randomization. If participants do not meet the above criteria, treatment with inhaled steroids and bronchodilators can be initiated if clinically indicated and eligibility can be reassessed after 1-2 weeks.
4. Adequate hematological, hepatic and renal function as defined in the protocol Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies
5. Other protocol defined inclusion criteria could apply
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E.4 | Principal exclusion criteria |
1. Participants with Mixed small cell with non-small cell lung cancer histology
2. Recent major surgery within 4 weeks prior to entry into the study
3. Significant acute or chronic infections
4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization
5. Active autoimmune disease that has required systemic treatment in past 1 year (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) Other protocol defined exclusion criteria could apply
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by Independent Review Committee (IRC) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time from randomization to final assessment at 8 years and 10 months |
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E.5.2 | Secondary end point(s) |
1. Occurrence of Treatment-emergent Adverse Events (TEAEs) and treatment-related Adverse Events (AEs)
2. Overall Survival
3. Changes from Baseline in pulmonary function
4. Programmed death-ligand 1 (PD-L1) expression in tumors at Baseline
5. Objective response according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
6. Duration of response
7. Pharmacokinetics profile of M7824 in terms of Ceoi and Ctrough
8. Immunogenicity of M7824 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Time from randomization to final assessment at 8 years and 10 months
2. Time from randomization to final assessment at 8 years and 10 months
3. Time from randomization to final assessment at 14 months
4. Randomization
5. Time from randomization to final assessment at 8 years and 10 months
6. Time from randomization to final assessment at 8 years and 10 months
7. Time from randomization to final assessment at 17 months
8. Time from randomization to final assessment at 17 months |
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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 | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Argentina |
Australia |
Brazil |
Canada |
China |
European Union |
Japan |
Korea, Republic of |
Russian Federation |
Taiwan |
Turkey |
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 the study is defined as the date of primary OS analysis when 254 participants have died. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 21 |