| Eligibility |
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:
- Absence of QTc prolongation (QTc > 450 msec on baseline ECG, using the Fridericia
correction [QTcF 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. A biopsy is mandatory at inclusion and after Cycle 2 (6 weeks) for patients from
phase I and a biopsy is mandatory at inclusion for patient from phase II. (Tumoral
material dated less than one month at inclusion is authorized).
- Patient affiliated to a social security regimen or beneficiary of the same according
- Validation by the sponsor of the quality of the tumoral material at inclusion
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 failure, QTcF prolongation >500 ms, electrolyte
disturbances, etc.), or patients with congenital long QT syndrome
- Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features
suggestive of MDS/AML
- History of another primary malignancy except for Malignancy treated with curative
intent and with no known active disease =5 years before the first dose of IP and of
low potential risk for recurrence Adequately treated non-melanoma skin cancer or
lentigo maligna without evidence of disease Adequately treated carcinoma in situ
without evidence of disease
- History of leptomeningeal carcinomatosis
- Patient with untreated central nervous system (CNS) metastases
- History of active primary immunodeficiency or Immunocompromised patients e.g, patients
who are known to be serologically positive for human immunodeficiency virus (HIV)
- Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients
with a past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for
hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative
for HCV RNA.
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of immunotherapy. The following are exceptions to this criterion:
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular
injection) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent Steroids as premedication for hypersensitivity reactions
(e.g., CT scan premedication)
- Receipt of live or live attenuated vaccine within 30 days prior to the first dose of
IP. Note: Patients, if enrolled, should not receive live vaccine (yellow fever
vaccination is forbidden) whilst receiving IP and up to 30 days after the last dose of
IP.
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 180 days after the last dose of treatment. (Contraceptive requirements:
Male patients must use a condom during treatment and for 3 months after the last dose
when having sexual intercourse with a pregnant woman or with a woman of childbearing
potential. Female partners of male patients should also use a highly effective form of
contraception if they are of childbearing potential.)
- Known allergy or hypersensitivity to any of the study drugs or any of the study drugs
excipients
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