A prospective, controlled, randomized, multicenter study whose goal is to compare the
efficacy of a chloroquine analog (GNS561), an anti PD-1 (nivolumab) and an
anti-interleukine-6 receptor (tocilizumab) versus standard of care in patients with advanced
or metastatic cancer who have Sars-CoV-2 infection not eligible to a resuscitation unit.
According to their severity level at the time of enrolment, eligible patients will be
randomized into 2 different cohorts:
- COHORT 1 (mild symptoms or asymptomatic): GNS561 vs anti-PD1 vs standard of care
(randomization ratio 1:1:1).
- COHORT 2 (moderate/severe symptoms): GNS561 vs anti-IL6 vs standard of care
(randomization ratio 1:1:1).
I1. Age 18 or older at the time of enrolment. I2. Histologically or cytologically confirmed
diagnosis of advanced or metastatic hematological or solid tumor (hematological or solid
tumor, any type and any localization).
I3. Documented diagnosis of COVID-19 (diagnostic test performed in a certified laboratory)
or symptoms of COVID-19 associated with radiological signs of pneumonia as described by Shi
et al.; I4. Cohort 2: patients with pneumonia confirmed by chest imaging, and an oxygen
saturation (Sao2) of 94% or less while they are breathing ambient air or a ratio of the
partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) (Pao2:Fio2) at
or below 300 mg Hg.
I5. Patient not eligible for a transfer to Resuscitation Unit (either due to underlying
medical condition - including cancer - or due to lack of available bed).
I6. Life-expectancy longer than 3 months.
I7. Adequate bone marrow and end-organ function defined by the following laboratory
- Bone marrow:
- Hemoglobin ≥ 7.0 g/dL,
- Absolute Neutrophils Count (ANC) ≥ 1.0 Gi/L,
- Platelets ≥ 100 Gi/L;
- Hepatic function:
- Total serum bilirubin ≤ 1.5 x ULN (except patients with Gilbert's syndrome who
must have total serum bilirubin ≤ 3.0 x ULN),
- AST and ALT ≤ 5 ULN
- Renal function:
- Serum creatinine ≤ 2.0 x ULN or Cr. Cl. ≥ 30ml/min/1.73m² (MDRD or CKD-EPI
formula); I8. Willingness and ability to comply with the study requirements; I9.
Signed and dated informed consent indicating that the patient has been informed
of all the aspects of the trial prior to enrolment (in case of emergency
situation, please refer to protocol section 13.1 PATIENT INFORMATION AND INFORMED
CONSENT); I10. Women of childbearing potential (Appendix 2) are required to have
a negative serum pregnancy test within 72 hours prior to study treatment start. A
positive urine test must be confirmed by a serum pregnancy test; I11. Women of
childbearing potential and male patients must agree to use adequate highly
effective contraception (Appendix 2) for the duration of study participation and
up to 6 months following completion of therapy; I12. Patient must be covered by a
E1. For cohort 1 only : Patient currently receiving therapy with an anti- PD-1, anti-
PD-L1, or anti-CTLA4.
E2. For cohort 2 only: Patient currently receiving therapy with an anti- IL-6 or
E3. Contraindication to treatment with nivolumab (cohort 1 only) or to tocilizumab (cohort
2 only) as per respective SPC, including known hypersensitivity to one of these study drugs
or severe hypersensitivity reaction to any monoclonal antibody.
E4. Patient known to have intolerance or hypersensitivity to chloroquine or any quinoline
derivates (e.g., quinine, chloroquine, mefloquine).
E5. Patient has active autoimmune disease that has required systemic treatment in the past
3 months before the date of randomisation or a documented history of clinically severe
autoimmune disease, or a syndrome that requires systemic steroids at doses higher than 10
mg/d prednisone equivalents or immunosuppressive agents.
Note 1: Patients with vitiligo or resolved childhood asthma/atopy would be an exception to
this rule. Patients that require intermittent use of bronchodilators or local steroid
injections would not be excluded from the study. Patients with hypothyroidism stable on
hormone replacement or Sjögren's syndrome will not be excluded from the study.
Note 2: Patients may receive corticosteroids as required for the management of
E6. Patient requires the use of one of the following forbidden treatment during the study
- Major surgery.
- Live vaccines. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, chicken pox, yellow fever and BCG. Seasonal
influenza vaccines for injection are generally killed virus vaccines and are allowed;
however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines,
and are not allowed.
E7. Significant cardiovascular disease, such as New York Heart Association cardiac disease
(Class II or greater), myocardial infarction within 3 months prior to the date of
randomisation unstable arrhythmias or unstable angina, Known Left Ventricular Ejection
Fraction (LVEF) < 50%.
Note: Patients with known coronary artery disease, congestive heart failure not meeting the
above criteria must be on a stable medical regimen that is optimized in the opinion of the
treating physician and in consultation with a cardiologist if appropriate.
E8. Patient has Active hepatitis B (chronic or acute; defined as having a positive
hepatitis B surface antigen [HBsAg] test at screening), Active hepatitis C (Patients
positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV
RNA at screening) or Human Immunodeficiency Virus (HIV) infection (HIV 1/2 antibodies).
E9. Prior allogeneic bone marrow transplantation or solid organ transplant in the past.
E10. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's participation
for the full duration of the trial, or is not in the best interest of the subject to
participate, in the opinion of the treating Investigator.
E11. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
E12. Pregnant or breastfeeding patient, or expecting to conceive children within the
projected duration of the trial, starting with the screening visit through 6 months after
the last dose of study drugs.