📋 Eligibility rules (as published)
Inclusion Criteria:
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
* Patients must be diagnosed with a metastatic or locally advanced non squamous non-small cell lung cancer
* Absence of previous treatment for or locally advanced or metastatic non-small cell lung cancer. Previous adjuvant therapy is allowed if \> 12 months from the last injection
* Age \>18 years at time of study entry
* Performance status ECOG of 0 or 1
* Life expectancy ≥ 6 months
* PD-L1\<50% using TPS scoring
* At least one lesion measurable as defined by standard imaging criteria for the patient's tumor type (RECIST v1.1) that can be accurately assessed at baseline and is suitable for repeated assessment
* Body weight \>30 kg
* Adequate normal organ and marrow function as defined below:
* Adequate cardiac function:
(QTc \< 450 msec on baseline ECG, using the Fridericia correction cQTcF formula) or other clinically significant ventricular or atrial arrhythmia.
Left ventricular ejection fraction (LVEF) ≥ 50%
* Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
* Patient affiliated to a social security regimen or beneficiary of the same according
* Validation of the quality and quantity of the tumoral material at inclusion (existing material dated less than one month and/or fresh biopsy).
* Patient is willing to perform the fresh biopsies mandatory for the protocol:
Phase I: A mandatory fresh biopsy of 4 samples at inclusion and after Cycle 2 (betweenC2J7 and C2J14) Phase II: A mandatory fresh biopsy. of 4 samples at inclusion. Second biopsy at 4-5 weeks after treatment initiation is optional.
Exclusion Criteria:
* Participation in another clinical study with an investigational product during the last 2 months
* Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
* Presence of EGFR, ROS or ALK targetable mutations
* Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, ototoxicity, vitiligo, and the laboratory values defined in the inclusion criteria. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable before the first dose of study drug
* Major surgical procedure within 28 days prior to therapy initiation IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48 hour interval must be maintained before the first dose of study drug
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea or malabsorption syndrome).
* History of allogenic organ, bone marrow or double umbilical cord blood transplantation
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
Patients with vitiligo or alopecia Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the study physician Patients with celiac disease controlled by diet alone
* History of glaucoma, any retinal pathology considered to be a risk factor for central serous retinopathy, retinal vein occlusion (RVO) or neovascular macular degeneration. Also, any risk factors for RVO as intraocular pressure (IOP) \>21, uncontrolled blood glucose
* Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease. Any uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure (including history of myocardial infarction within 3 months, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or any cardiac arrhythmias, e.g, ventricular, supraventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening) uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high Resolution Computed Tomography (HRCT) sacan or any psychiatric disorder that prohibits obtaining informed consent.
* Currently taking medications with known risk of prolonging the QT interval or inducing Torsades de Pointes
* Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart
HealthTeky