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

Non Small Cell Lung Cancer Clinical Trial

— OPTIMUNELUNG  

Official title:

Integrative Analysis of the Tumor Microenvironment and Optimization of the Immunotherapy Duration in Non-small Cell Lung Cancer Patients (OPTIMUNE-LUNG Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04880382
• Other study ID #: IB 2019-07
• Secondary ID: 2020-005562-34
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 27, 2021
• Est. completion date: August 2026

Study information

• Verified date: January 2024
• Source: Institut Bergonié
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: August 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• ICI treatment discontinuation
After achieving objective response between 6 and 12 months after treatment onset, for these patients, first or second line treatment by immune checkpoint inhibitor will be discontinued. Patients will be followed as per standard mangement thereafter
• ICI treatment continuation
After achieving objective response between 6 and 12 months after treatment onset, for these patients, first or second line treatment by immune checkpoint inhibitor will be continued until disease progreession or unacceptable toxicity

Locations

Country	Name	City	State
France	Centre Hospitalier de la Côte Basque	Bayonne
France	Clinique Tivoli Ducos	Bordeaux
France	Institut Bergonie	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Clinique Marzet	Pau

Sponsors (1)

Lead Sponsor	Collaborator
Institut Bergonié

Country where clinical trial is conducted

France, 

Outcome

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