Integrative analysis of the tumor microenvironment and optimization of the immunotherapy duration in non-small cell lung cancer patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Bergonie

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Aug 2021 → 23 Feb 2026

Decision date (initial)

2024-06-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509490-23-00

EudraCT number

2020-005562-34

ClinicalTrials.gov

NCT04880382

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Therapy, Pharmacogenomic, Efficacy

The primary objective is 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).

Secondary objectives 5

1. To 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).
2. To describe retreatment for arm B-patients and subsequent systemic therapies for arm A-patients.
3. 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.
4. 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.
5. To assess the safety profile of each therapeutic strategy (NCI-CTCAE v5).

Conditions and MedDRA coding

Patients with locally advanced or metastasic Non-Small Cell Lung Carcinoma.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Histologically or cytologically confirmed non-small cell lung carcinoma (squamous or non squamous).
2. Locally advanced/unresectable or metastatic disease.
3. For non-squamous histology, tumor with no oncogenic addiction: no activating EGFR mutation, no ALK or ROS1 rearrangement,
4. 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.
5. 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.
6. 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.
7. 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).
8. Age ≥ 18.
9. Performance status < 2.
10. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration.
11. Patient with a social security in compliance with the French law (Loi Jardé).
12. Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
13. Voluntarily signed and dated written informed consent prior to any study specific procedure.

Exclusion criteria 6

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 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).
2. The 12-month PFR will be assessed, independently for each therapeutic strategy.
3. Imaging will be centrally reviewed for all patients by an expert radiologist. Reviewed data will be used for the primary endpoint analysis.

Secondary endpoints 8

1. Secondary endpoints will be assessed, independently for each therapeutic strategy:
2. 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.
3. 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.
4. 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.
5. Overall Survival (OS) defined as the time interval between the date of randomization and the date of death (of any cause).
6. 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.
7. 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.
8. Biomarker study: integrated analysis of blood samples and tumor biopsies performed at randomization and progression to reveal markers of response and resistance.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Bergonie

Sponsor organisation

Institut Bergonie

Address

229 Cours De L Argonne

City

Bordeaux

Postcode

33000

Country

France

Scientific contact point

Organisation

Institut Bergonie

Contact name

Pr Antoine ITALIANO

Public contact point

Organisation

Institut Bergonie

Contact name

David JUZANX

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications