De-escalation Immunotherapy mAintenance Duration Trial for Stage IV Lung Cancer Patients With Disease Control After Chemo-immunotherapy Induction

Exclusion Criteria24

• Small cell lung cancer or tumors with mixed histology including a SCLC component.
• Note : Sarcomatoid histology is allowed. Neuro-endocrine large cell lung cancer with molecular features of small-cell lung cancer (i.e; Rb loss associated with TP53 mutation) will not be eligible. Other neuro-endocrine large cell subtypes, i.e. with adenocarcinoma features (STK11 or K-Ras mutations) will be eligible. In case of doubt, please contact the sponsor.
• Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18, exon 20 insertion) or HER2 exon 20 insertion (either tissue or plasma cfDNA mutation).
• Known ALK, ROS1, Ret, NTRK, NRG1 gene rearrangement as assessed by immunohistochemistry, FISH or NGS (ADN or ARN) sequencing by local genetics and/or pathology laboratory.
• Previous or active cancer within the previous 3 years (except for treated carcinoma in situ of the cervix, or basal cell skin cancer treated or not). Patients with a prostate adenocarcinoma history within the previous 3 years could be included in case of localized prostate cancer, with good prognostic factors according to d'Amico classification (≤T2a, score de Gleason ≤ 6 and PSA ≤ 10 (ng/ml)) provided they were treated in a curative way (surgery or radiotherapy, without any chemotherapy).
• Superior vena cava syndrome persisting despite VCS stenting.
• Radiotherapy needed at initiation of tumour treatment, except bone palliative radiotherapy on a painful or compressive metastasis, respecting 1 week delay between the end of radiotherapy and the beginning of treatment
• Symptomatic untreated brain metastasis (without previous whole brain radiotherapy or stereotactic ablative brain radiotherapy or without surgical resection). At least 2 weeks delay between the end of radiotherapy and the beginning of induction immunotherapy treatment should be respected. Asymptomatic brain metastasis, not needing corticosteroids greater than 10 mg prednisone equivalent daily or mannitol infusions, are allowed.
• History of previous primary immunodeficiency, organ transplantation needing an immunosuppressive treatment, any immunosuppressive drug within 28 days before randomization date, or history of severe toxicity (grade 3/4) by immune mechanism linked to another immunotherapy treatment.
• Systemic treatment with corticosteroids with greater dose than 10 mg prednisone equivalent daily, within 14 days before initiation of the immunotherapy induction. Inhaled, nasal or topic corticosteroids are allowed.
• History of active autoimmune disease including but not limited to rheumatoid polyarthritis, myasthenia, autoimmune hepatitis, systemic Lupus, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome with interstitial pulmonary disease, recent Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• Patients with type I diabetes, or hypothyroidism, or immune cutaneous disease (vitiligo, psoriasis, alopecia) or benign rheumatoid polyarthritis not needing any immunosuppressive systemic treatment, or benign sicca syndrome (Sjogren) without interstitial pulmonary disease, or history of past Guillain-Barre syndrome, totally reversible with no sequelae, no systemic immunosuppressive treatment during the last 20 years, are allowed to be included.
• Active inflammatory intestinal disease (Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea.
• Active uncontrolled infection including tuberculosis, known acute viral hepatitis B and C according to serological tests. Patients with serological sequelae of cured viral hepatitis are allowed to be included. Past primary pulmonary tuberculosis in youth does not consist of a contra-indication. Past tuberculosis disease history does not consist of a contra-indication provided the patient was treated during at least 6 months by anti-tuberculosis antibiotic treatment.
• Known HIV infection
• Living attenuated vaccine received within the 30 previous days
• Previous treatment with anti-PD-1, anti-PD-L1, Anti-CTLA4 or any ICI antibody
• Previous treatment with chemotherapy for lung cancer. However, if a patient has a lung adenocarcinoma, previous cisplatin treatment for another cancer type with squamous histology (Head and Neck, bladder) may be allowed provided the sponsor accepts, and provided blood tests are normal (see above).
• General serious condition such as congestive uncontrolled cardiac failure, uncontrolled cardiac arrythmia, uncontrolled ischemic cardiac disease (unstable angina or history of myocardial infarction within the previous 6 months), history or stroke within the 6 previous months. Patients with a significant cardiac history, even if controlled, should have a LVEF \> 50%.
• Pre-existing moderate or severe lung interstitial disease as assessed by the diagnosis CT-scan.
• Inability to comply with study and/or follow-up procedures for family, social, geographic or psychological reasons.
• Pregnant, lactating, or breastfeeding women.
• Patients deprived of liberty by judicial or administrative decision
• Patient who is subject to legal protection or who is unable to express his will