Study Investigating the Association of NP137 With Atezolizumab-Bevacizumab Combination in First Line in Unresectable HCC

Inclusion Criteria: 1. Males or females ≥ 18 years of age 2. Histologically confirmed (liver biopsy within 24 previous weeks) and documented unresectable hepatocellular carcinoma 3. Patients with a BCLC C or BCLC B status ineligible for or in failure of locoregional treatment, as per the Barcelona Clinic Liver Cancer (BCLC) staging system 4. No prior systemic therapy for advanced HCC 5. Liver tumor burden \< 50% of the liver (per Investigator judgment) 6. Child-Pugh A (≤ 6) without any history of cirrhotic decompensation within the past 6 months 7. Antiviral therapy required in hepatitis B virus patients (Hepatitis B antigen positive) 8. Willing to have liver biopsy between C4 and C5 9. Presence of a measurable tumor per RECIST v1.1 criteria 10. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 11. Life expectancy ≥ 12 weeks 12. Absence of previous liver decompensation 13. In case of cirrhosis, last esophageal varices detection by esogastroduodenal endoscopy have to be performed within last the 6 months before inclusion 14. Adequate hematologic function prior to the first dose of NP137, defined as: Absolute neutrophils count ≥ 1500 cells/μL 14.2. Hemoglobin ≥ 9 g/dL with no transfusion within 4 weeks prior to first planned dose of NP137 14.3. Platelet count \> 50,000/μL with no transfusion within 2 weeks prior to first planned dose of NP137 15. Adequate renal function prior to first dose, defined as: 15.1. Serum creatinine \< 1.5 × Upper limit of normal (ULN ) 15.2. Creatinine clearance ≥ 30 mL/min/m2 (by Cockroft-Gault equation of 24-hour urine) if creatinine ≥ 1.5 × ULN 16. Adequate hepatic function prior first dose, defined as AST/ALT ≤ 5 × ULN 17. Women patients of childbearing potential must have a negative serum pregnancy test at screening and baseline, and be willing to use a highly effective contraception. The patient should be advised to continue the contraception for at least 6 months following the completion of dosing. Women with cessation for \> 24 months of previously occurring menses, or women of any age who have had a hysterectomy, or have had both ovaries removed will be considered to be of non-childbearing potential. 18. Male patients of reproductive potential must be willing to use one acceptable method of contraception, as judged by Investigator and Sponsor and/or to refrain from donating sperm from the time of screening through at least 6 months following the completion of dose administration. 19. Amenable to computed tomography (CT) with 3 or 4 phase liver or magnetic resonance imaging (MRI) of abdomen and pelvis, and CT of chest, or MRI of whole body, for initial tumor size measurements and subsequent follow-up. 20. Absence of other clinically relevant abnormalities for any screening laboratory test results as judged by the Investigator and Sponsor. 21. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 22. Able to understand and provide written informed consent 23. Patients covered by Health Insurance System Exclusion Criteria: 1. Any known history of encephalopathy within 6 months prior to first planned dose of treatment 2. Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding 3. Known esophageal varices with recent history of bleeding (within previous 6 months) 4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures 5. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC 6. Chronic treatment with immunosuppressive agents (like steroids) ≤ 6 weeks prior to first planned dose of treatment. 7. Major surgical procedures, open biopsy or significant traumatic injury ≤ 4 weeks prior to first dose of treatment or anticipation of major surgical procedure during the course of the trial, minor surgical procedures ≤ 1 week of first planned dose (the surgical wound must be fully healed) 8. Local therapy to liver within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure 9. Any clinically significant cardiovascular condition as judged by the Investigator (such as New York Heart Association Class II or greater cardiac failure, myocardial infarction, or cerebrovascular accident within 3 months prior to Day 1 of Cycle 1, uncontrolled arterial hypertension, unstable arrhythmia, or unstable angina) 10. Severe or uncontrolled renal condition 11. Untreated chronic hepatitis B 12. Co-infection of HBV and HCV 13. Use of any prohibited concomitant medications within 14 days of the Baseline/Day 1 visit 14. Contraindication to additionnal liver biopsy planned between C4 and C5 15. Contraindication to iodinated contrast agent infusion 16. Known current alcohol (\> 20g/ Day in women and \> 30g/ Day in men) or substance abuse 17. History of leptomeningeal disease 18. Active or history of autoimmune disease or immune deficiency 19. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan 20. Known active tuberculosis 21. History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death 22. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 6 months after the last dose of treatment 23. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases 24. Uncontrolled tumor-related pain 25. Uncontrolled or symptomatic hypercalcemia 26. Treatment with systemic immunostimulatory agents 27. Inadequately controlled arterial hypertension 28. Prior history of hypertensive crisis or hypertensive encephalopathy 29. Evidence of bleeding diathesis or significant coagulopathy 30. History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration 31. Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture 32. Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses 33. Known clinically significant or life threatening organ or systemic disease such that in the opinion of the Investigator, the significance of the disease will compromise the patient\'s participation in the trial 34. Known intolerance or hypersensitivity to the active ingredient or to one of the components of the study drug 35. Persistent toxicities related to prior treatment of grade greater than 1 36. Subjects with active infection 37. History of bone marrow allograft or solid organ transplant 38. Subjects requiring corticosteroid therapy at a dose equivalent to more than 10 mg of prednisone equivalent dose per day (corticosteroid administration is permitted by a route resulting in minimal systemic exposure \[cutaneous, rectal, articular, ocular or inhalation\] is authorized). 39. Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies 40. History of gastrointestinal perforations and fistulae 41. Uncontrolled or symptomatic proteinuria 42. Active aneurysm considered as unstable and/or at high risk of complication 43. Patients who experienced immune-mediated pericardial disorders during previous treatment by immune checkpoint blockade therapies, including anti-CTLA4, anti-PD1, and anti-PDL1 therapeutic antibodies 44. Subject who participate or plan to participate in another interventional clinical trial or who is in exclusion period for another study, 45. Subject who cannot be contacted in case of emergency 46. Persons referred to in Articles L1121-5 to L1121-8 of the French code of public health (this corresponds to all persons protected: pregnant or parturient women, breastfeeding mothers, persons deprived of liberty by judicial or administrative decision, persons subject to a legal protection measure).