Clinical trial NCT04880382: Integrative Analysis of Tumor Microenvironment and Optimization of Immunotherapy Duration in NSCL Cancer Patients
Official title: Integrative Analysis of the Tumor Microenvironment and Optimization of the Immunotherapy Duration in Non-small Cell Lung Cancer Patients (OPTIMUNE-LUNG Study)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: Immune checkpoint inhibition
non-small cell lung cancer
treatment duration
long-term benefit
Lead sponsor: Institut Bergonié
Sponsor class: OTHER
First posted: 2021-05-10
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized phase II study in which eligible patients will be randomized (1:1) according to two therapeutic strategies
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 12 months
Secondary outcomes:
measure: Assessment of secondary resistance in NSCLC patients who experienced a response to PD1/PDL-1 inhibition
timeFrame: 12 months
measure: Duration of response independently for each therapeutic strategy
timeFrame: Throughout the treatment period, an expected average of 12 months
measure: 1-year progression-free survival, independently for each therapeutic strategy
timeFrame: 1 year
measure: 2-year progression-free survival, independently for each therapeutic strategy
timeFrame: 2 years
measure: 1-year overall survival, independently for each therapeutic strategy
timeFrame: 1 year
measure: 2-year overall survival, independently for each therapeutic strategy
timeFrame: 2 years
measure: Safety profile, independently for each therapeutic strategy: Common Terminology Criteria for Adverse Events version 5
timeFrame: Throughout the treatment and follow-up period, an expected average of 12 months
measure: • To describe retreatment for arm B-patients and subsequent systemic therapies for arm A-patients
timeFrame: Throughout the treatment and follow-up period, an expected average of 12 months
measure: Tumor immune cells levels
timeFrame: At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)
measure: Blood cytokines levels
timeFrame: At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)
measure: Blood lymphocytes levels
timeFrame: At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)
measure: Blood kynurenine levels
timeFrame: At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)
Other outcomes:
Locations:
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque
city: Bordeaux
country: France
facility: Clinique Tivoli Ducos
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Pau
country: France
facility: Clinique Marzet
Study officials:
References: