Integrative Analysis of Tumor Microenvironment and Optimization of Immunotherapy Duration in NSCL Cancer Patients

Phase 2

Active, not recruiting

• Conditions: Non Small Cell Lung Cancer
• Interventions: Drug: ICI treatment continuation; Drug: ICI treatment discontinuation

• Registration Number: NCT04880382
• Lead Sponsor: Institut Bergonié

Brief Summary

Non-comparative multicentric randomized study 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)

Detailed Description

Two-arm, non-comparative, prospective, multicentric, randomized study for early discontinuation of immune checkpoint inhibitor PD1/PDL-1 blockade therapy in non-small cell lung cancer patients who achieved objective response between 6 and 12 months after treatment onset.

Study Timeline

• Study First Submitted: 2021-04-30
• Study First Submitted QC: 2021-05-05
• Study First Posted: 2021-05-10
• Study Start: 2021-08-27
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-26
• Last Update Posted: 2024-01-30
• Primary Completion: 2025-08
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

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):

   1. in first or second-line treatment as per market authorization. For patients in first line, ICI alone or ICI + chemotherapy,
   2. 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 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

7. At least one lesion that can be biopsied for research purpose.

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

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Arm A: treatment by ICI will be continued	ICI treatment continuation	After achieving objective response between 6 and 12 months after treatment onset, for these patients ICI treament will continue as per market authorization
Experimental Arm B: treatment by ICI will be discontinued	ICI treatment discontinuation	After achieving objective response between 6 and 12 months after treatment onset, for these patients first-line or second line regimen should be discontinued. Patients will be followed as per standard management.

Primary Outcome Measures

Name	Time	Method
Assessment of the long-term benefit of PD-1 inhibition in NSCLC patients who experienced a response between 6 and 12 months after initiation of ICI	12 months	Long-term benefit will be assessed in terms of progression-free rate (PFR) at 12 months after randomization, for each therapeutic strategy

Secondary Outcome Measures

Name	Time	Method
Assessment of secondary resistance in NSCLC patients who experienced a response to PD1/PDL-1 inhibition	12 months	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, independently for each therapeutic strategy
Safety profile, independently for each therapeutic strategy: Common Terminology Criteria for Adverse Events version 5	Throughout the treatment and follow-up period, an expected average of 12 months	Toxicity graded using the Common Terminology Criteria for Adverse Events version 5
1-year progression-free survival, independently for each therapeutic strategy	1 year	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
Duration of response independently for each therapeutic strategy	Throughout the treatment period, an expected average of 12 months	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
• To describe retreatment for arm B-patients and subsequent systemic therapies for arm A-patients	Throughout the treatment and follow-up period, an expected average of 12 months	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
Blood lymphocytes levels	At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)	Levels of lymphocytes in blood will be measured by flow cytometry
2-year progression-free survival, independently for each therapeutic strategy	2 years	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
1-year overall survival, independently for each therapeutic strategy	1 year	Overall Survival (OS) defined as the time interval between the date of randomization and the date of death (of any cause)
2-year overall survival, independently for each therapeutic strategy	2 years	Overall Survival (OS) defined as the time interval between the date of randomization and the date of death (of any cause)
Tumor immune cells levels	At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)	Levels of immune cells in tumor will be measured by immunohistochemistry.
Blood kynurenine levels	At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)	Levels of kynurenine in blood will be measured by ELISA
Blood cytokines levels	At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)	Levels of cytokines in blood will be measured by ELISA

Trial Locations

Locations (5)

Clinique Tivoli Ducos; 🇫🇷 Bordeaux, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Polyclinique Bordeaux Nord Aquitaine; 🇫🇷 Bordeaux, France

Centre Hospitalier de la Côte Basque; 🇫🇷 Bayonne, France

Clinique Marzet; 🇫🇷 Pau, France