E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage III non-small cell lung cancer |
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E.1.1.1 | Medical condition in easily understood language |
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 |
Clinical activity - To compare the antitumor activity of durvalumab alone vs durvalumab in combination with novel agents. |
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E.2.2 | Secondary objectives of the trial |
Safety - To evaluate the safety and tolerability of durvalumab alone and durvalumab in combination with novel agents.
Clinical activity - To further compare the efficacy of durvalumab alone vs durvalumab in combination with novel agents.
Pharmacokinetics (a) To describe the pharmacokinetics (PK) of durvalumab alone and durvalumab in combination with novel agents. (b) To describe the PK of novel agents in combination with durvalumab.
Immunogenicity (a) To assess the immunogenicity of durvalumab alone or in combination with novel agents (b) To assess the immunogenicity of novel biologic agents in combination with durvalumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluation 2. Age 18 years or older 3. Body weight ≥ 35 kg 4. Subjects must have histologically or cytologically documented NSCLC who present with locally advanced, unresectable, Stage III disease 5. Subjects must have completed, without progressing, definitive cCRT within 42 days prior to being randomized into the study. 6. Subjects must have at least one previously irradiated tumor lesion that can be measured by RECIST v1.1 7. Provision of tumor tissue sample, when available, from original diagnosis obtained before initiation of chemoradiotherapy 8. Life expectancy ≥ 12 weeks 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 |
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E.4 | Principal exclusion criteria |
1. Mixed small cell and non-small cell lung cancer histology 2. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. 3. Prior exposure to any anti-PD-1, anti-PD-L1, or anti-cytoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody for the treatment of NSCLC. 4. Subjects with history of ≥ Grade 2 pneumonitis from prior chemoradiation therapy 5. Subjects with a history of venous thrombosis within the past 3 months 6. Subjects with history of myocardial infarction, transient ischemic attack, or stroke in the past 6 months 7. Congestive heart failure 8. Active or prior documented autoimmune or inflammatory disorders 9. History of active primary immunodeficiency 10. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) 11. History of allogenic organ transplantation 12. QTcF interval ≥ 470 ms 13. History of another primary malignancy 14. Concurrent enrollment in another therapeutic clinical study or during the follow-up period of an interventional study. Enrollment in observational studies will be allowed 15. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical activity - Objective response (OR) per Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST v1.1) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization until documention of disease progression, or the last evaluable disease assessment in the absence of PD prior to the initiation of subsequent anticancer therapy or discontinuation from the study, whichever occurs first. |
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E.5.2 | Secondary end point(s) |
Safety - Presence of adverse events (AEs), serious adverse events (SAEs), and abnormal laboratory parameters and vital signs.
Clinical activity - Duration of response (DoR), disease control (DC), progression-free survival (PFS) at 12 months, and PFS per RECIST v1.1 and overall survival (OS).
Pharmacokinetics - Concentration of durvalumab or novel agents in serum.
Immunogenicity - Antidrug antibody (ADA) incidence of durvalumab or novel biologic agents |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety - From time of informed consent through treatment period (12 months) or up to 3 months post last dose of study treatment.
DoR - From randomization until documention of disease progression.
DC - From randomization until progression, or the last evaluable disease assessment in the absence of PD prior to the initiation of subsequent anticancer therapy or discontinuation from the study, whichever occurs first.
PFS and OS - From start of treatment until study completion or death, whichever comes first.
Pharmacokinetics and immunogenicity - During the treatment period and follow-up. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Canada |
France |
Germany |
Hong Kong |
Italy |
Poland |
Portugal |
Spain |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 (“study completion”) is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last subject in the study. This date will be 5 years after the final subject is entered into the study or when the sponsor stops the study, whichever occurs first. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |