E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non small cell lung cancer stage III after concurrent chemoradiation therapy |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029520 |
E.1.2 | Term | Non-small cell lung cancer stage IIIA |
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 | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
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 | 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 explore whether BI 1361849 (CV9202) prolongs progression-free survival (PFS) in comparison to placebo (sham-vaccine).
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E.2.2 | Secondary objectives of the trial |
- To determine whether BI 1361849 (CV9202) prolongs overall survival (OS).
- To assess other efficacy criteria.
- To analyse immunogenicity of BI 1361849 (CV9202).
- To assess the safety and tolerability of BI 1361849 (CV9202).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histopathologically and/or cytologically confirmed inoperable, locally advanced non-small cell lung cancer (NSCLC) Stage IIIA or IIIB at diagnosis, absence of metastases confirmed by radiological evaluation including brain imaging (Computer tomography (CT) or Magnetic Resonance Imaging (MRI) and/or Positron emission tomography scan).
- Previous concurrent chemoradiation therapy with the last chemotherapy dose administered >= 28 days and the last radiation dose received <= 84 days before randomisation.
- Chemotherapy must have been platinum-based and consisted of 2 to 4 three-weekly or four-weekly cycles of doublet chemotherapy, and concurrent radiotherapy dose was 60 to 70 Gy in fractions of 1.8 - 2.0 Gy (daily biologically equivalent doses) and not conventional 2-dimensional therapy. Overlap of radiotherapy with a minimum of 2 cycles of the platinum-based chemotherapy is required. A deviation of up to 3 days from an exact overlap is acceptable.
- Patient has radiologically assessed objective response (Complete Response, Partial Response) or at least stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as response to chemoradiation at the first post-chemoradiation imaging maintained at the last imaging prior to randomisation.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. |
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E.4 | Principal exclusion criteria |
- Proton therapy was part of the prior chemoradiation therapy to treat NSCLC.
- Malignant effusion at diagnosis or any other time prior to start of chemoradiation. Malignancy of effusion must be excluded by analysis of the fluid, e.g. for pleural effusion by samples taken at 2 separate paracentesis time points, being negative for exudate and for blood and malignant cells. If at screening effusion is too small to be amenable to paracentesis and in the view of the investigator is unlikely to reflect malignancy, the patient is eligible.
- Distant metastasis. Absence of brain metastasis needs to be confirmed by imaging (CT, MRI) after chemoradiation therapy and prior to randomisation.
- Any previous or ongoing systemic treatment of NSCLC before randomisation, other than completed concurrent chemoradiation therapy as defined in this protocol. Supportive or alternative / complementary treatment with no relevant effect on the immune system is permitted.
- Major surgery (based on investigator's judgement) for NSCLC other than diagnostic or staging biopsies prior to randomisation.
- Condition requiring chronic immunosuppressive treatment including systemic steroid doses of >= 10 mg prednisone equivalent per day.
- Major inflammatory events including colitis, thyroiditis, or hepatitis within 28 days before randomisation.
- Known pre-existing interstitial lung disease, including pneumonitis of Common Terminology Criteria for Adverse Events grade >1 at screening.
- Known autoimmune disorder (incl. type I diabetes, rheumatoid arthritis, multiple autoimmune endocrine disorders) or immunodeficiency. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1: Progression-free survival (PFS), defined as time (days) from the date of randomisation to the date of progression or to the date of death, whichever occurs first.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1: 52, 90 and 156 weeks after the last patient was randomized and follow-up until 3.5 years after the last randomization
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E.5.2 | Secondary end point(s) |
1: PFS status at 52 weeks after randomisation.
2: PFS2, defined as time (days) from randomisation to either death or disease progression by investigator assessment occurring after initiation of 1st subsequent systemic anti-cancer therapy.
3: Immune response status.
4: Symptomatic progression, defined as time (days) from randomisation to an increase of at least 10 points from baseline for one or more of cough (Q1, QLQ-LC13), dyspnoea (Q3-5, QLQ-LC13) or chest pain (Q10, QLQ-LC13) based on the EORTC QLQ-LC13.
5: Discontinuation of study treatment by 24 weeks after randomisation either due to an adverse event not related to tumour or due to patient withdrawal from study treatment for drug associated reasons.
6: Overall survival (OS), defined as time (days) from the date of randomisation to the date of death.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: 52 weeks after randomization
2: 52, 90 and 156 weeks after the last patient was randomized and follow-up until 3.5 years after the last randomization
3: 52 weeks after the last patient has been randomized
4: 52, 90 and 156 weeks after the last patient was randomized and follow-up until 3.5 years after the last randomization
5: 24 weeks after randomization
6: 52, 90 and 156 weeks after the last patient was randomized and follow-up until 3.5 years after the last randomization
6: 52, 90 and 156 weeks after the last patient was randomized and follow-up until 3.5 years after the last randomization
6: 52, 90 and 156 weeks after the last patient was randomized and follow-up until 3.5 years after the last randomization
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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 | No |
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 | 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) | No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
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 |
Denmark |
France |
Germany |
Japan |
Korea, Republic of |
Netherlands |
Norway |
Poland |
Portugal |
Spain |
Taiwan |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 14 |