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

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

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: ICI treatment continuation; Drug: ICI treatment discontinuation

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sophie COUSIN, MD; Phone Number: +33 5.56.33.33.33; Email: s.cousin@bordeaux.unicancer.fr

Study Locations

• France
  • Bayonne, France, 64109
    • Centre Hospitalier de la Côte Basque
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Bordeaux, France, 33000
    • Clinique Tivoli Ducos
  • Bordeaux, France, 33077
    • Polyclinique Bordeaux Nord Aquitaine
  • Pau, France
    • Clinique Marzet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard Arm A: treatment by ICI will be continued; After achieving objective response between 6 and 12 months after treatment onset, for these patients ICI treament will continue as per market authorization	Drug: 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
Experimental: Experimental Arm B: treatment by ICI will be discontinued; 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.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
• 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
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Institut Bergonié

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2021
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; treatment duration; Immune checkpoint inhibition; long-term benefit
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: IB 2019-07; 2020-005562-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No