| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| non-small cell lung cancer |
| cancer du poumon non à petites cellules |
|
| E.1.1.1 | Medical condition in easily understood language |
| advanced non-small cell lung cancer |
| cancer du poumon non à petites cellules avancés |
|
| 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 | SOC |
| E.1.2 | Classification code | 10029104 |
| E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 | 10059515 |
| E.1.2 | Term | Non-small cell lung cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 assess long-term benefit of PD-1 inhibition in NSCLC patients who experienced a response between 6 and 12 months after initiation of ICI (immune checkpoint inhibitor PD1/PDL-1 blockade therapy). The long-term benefit of PD1/PDL-1 inhibition will be assessed in terms of progression-free rate (PFR) at 12 months after randomization, for each therapeutic strategy (in patients discontinuing treatment and in patients continuing treatment). |
|
| E.2.2 | Secondary objectives of the trial |
•T o assess, for each therapeutic strategy:
o Secondary resistance in terms of progression rate at 12 months in NSCLC patients who experienced a response to PD1/PDL-1 inhibition,
o Duration of response (DR),
o 1- and 2-year Progression-free survival (PFS),
o 1- and 2-year Overall Survival (OS).
• To describe retreatment for arm B-patients and subsequent systemic therapies for arm A-patients.
• To assess specific peripheral and tumor microenvironment and genomic profile associated with long term benefit of PD1/PDL-1 inhibition despite treatment discontinuation in NSCLC patients.
• To assess specific peripheral and tumor microenvironment as well as genomic profile associated with secondary resistance in NSCLC patients who experienced a response to PD1/PDL-1 inhibition.
• To assess the safety profile of each therapeutic strategy (NCI-CTCAE v5). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed non-small cell lung carcinoma (squamous or non squamous).
2. Locally advanced/unresectable or metastatic disease.
3. Treatment with ICI (immune checkpoint inhibitor PD1/PDL-1 blockade therapy):
a. in first or second-line treatment as per market authorization. For patients in first line, ICI alone or ICI + chemotherapy,
b. start of ICI treatment 6 to 12 months (+/- 2 weeks) before registration.
4. At least one measurable lesion according to the RECIST v1.1 criteria before ICI treatment onset and confirmed by centralized review (lesion in previously irradiated filed can be considered as measurable if progressive at inclusion according to RECIST v1.1). At least one site of disease must be uni-dimensionally ≥ 10 mm.
5. Patient with objective response (CR, PR) according to RECIST v1.1 criteria at 6 months or more and less than 12 months after ICI treatment onset. Response must be confirmed by centralized review on the basis of all CT scan carried out since the initiation of ICI treatment up to registration. PET-CT are also acceptable (several PET-CTs or CT scans compared with PET-CTs), under the following conditions:
a. Target lesions must be evaluable on PET-CT according to RECIST v1.1. This will be determined by the centralized radiologist at the time of the review. If target lesions are not evaluable according to RECIST v1.1, patient will not be eligible.
b. PET-CT is acceptable only for the centralized review. If not available, an additional CT scan must be performed within four weeks prior to registration (+1 week tolerance) to be used as baseline tumor assessment. Patient must be then followed using the same technique throughout the duration of the protocol.
6. At least one lesion that can be biopsied for research purpose. Note that in case of complete response or too small size lesion, the investigator must ensure the availability of suitable paraffin embedded (FFPE) archived tumor material (primary or metastatic site).
7. Age ≥ 18.
8. Performance status ≤ 2.
9. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration.
10. Patient with a social security in compliance with the French law (Loi Jardé).
11. Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
12. Voluntarily signed and dated written informed consent prior to any study specific procedure.
|
|
| E.4 | Principal exclusion criteria |
1. Female who is pregnant or breast-feeding.
2. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
3. Hypersensitivity to one of the active substances or to one of the excipients
4. Any contraindication to pursue ICI treatment as per investigator judgement.
5. Previous enrolment in the present study.
6. Individual deprived of liberty or placed under legal guardianship.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• The primary endpoint is the 12-month progression-free rate (PFR) defined as the rate of patients in confirmed and unconfirmed complete reponse (CR and Cru), confirmed and unconfirmed partial response (PR and PRu) and stable disease (SD), as per RECIST v1.1, observed at 12 months (from randomization). To be considered as confirmed (i.e. as CR or PR), claimed responses will have to be confirmed 4 weeks later. Otherwise, responses will be considered as unconfirmed (CRu, PRu).
• The 12-month PFR will be assessed, independently for each therapeutic strategy.
• Imaging will be centrally reviewed for all patients by an expert radiologist. Reviewed data will be used for the primary endpoint analysis. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The PFR at 12 months will be reported independently for each population. |
|
| E.5.2 | Secondary end point(s) |
Secondary endpoints will be assessed, independently for each therapeutic strategy :
• The rate of patients who develop progression (as per RECIST v1.1) due to secondary resistance after obtaining a response to PD1/PDL-1 inhibition (secondary progression) will be assessed, independently for each therapeutic strategy, at 12 months from randomization, based on radiological centralized review.
• Duration of response (DoR) defined as the time interval between the first response (complete or partial response as per RECIST v1.1) to the time of the first documentation of disease progression.
• Progression-free survival (PFS) defined as the time interval between the date of randomization and the date of progression or death, whichever occurs first. Progression will be determined according to RECIST v1.1.
• Overall Survival (OS) defined as the time interval between the date of randomization and the date of death (of any cause).
• Toxicity profile of each therapeutic strategy will be assessed during the study. Events will be graded according to the Common Terminology Criteria of Adverse Events (CTCAE) v5 from the NCI. AEs and SAEs will be coded according to MedDRA.
• Number of patients retreated by ICI will be described in Arm B. Similarly, for arm A-patients, number of patients treated by subsequent systemic therapy will be described.
• Biomarker study: integrated analysis of blood samples and tumor biopsies performed at randomization and progression to reveal markers of response and resistance.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. The rate of patients who develop progression due to secondary resistance at 12 months will be reported independently for each population.
2. The DoR will be reported independently for each population once date of progression for the patient is known (RECIST 1.1)
3. Median PFS, 1- and 2-year PFS rates will be reported independently for each population.
4. Median OS, 1- and 2-year PFS rates will be reported independently for each population.
5. Safety will be assessed across the treatment period
6. Biomarker results will be reported independently for each population at baseline and at progression. |
|
| 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 | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| E.8.2.3 | Other | No |
| 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 | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
Print
