Atezolizumab for Hepatocellular carcinoma

Inclusion criteria

• {"criterion_text":"- Male or female"}
• {"criterion_text":"- Signed written Informed consent"}
• {"criterion_text":"- Aged ≥18 years at time of signing informed consent"}
• {"criterion_text":"- Presenting with HCC, diagnosed either by histological or radiological criteria as described by EASL"}
• {"criterion_text":"- Locally advanced or metastatic and/or unresectable HCC according a Multidisciplinary Team meeting"}
• {"criterion_text":"- Progressive disease after exposure to standard-of-care approved first-line immunotherapy-based"}
• {"criterion_text":"- Child-Pugh A within 7 days prior to inclusion"}
• {"criterion_text":"- ECOG Performance status 0 to 1"}
• {"criterion_text":"- Adequate hematological (Hemoglobin >8.5g/dL, platelets >60G/L, neutrophils >1.5G/L) and renal (creatinine clearance > 50 mL/min according to Cockcroft or MDRD formula) functions"}
• {"criterion_text":"- Disease measurable by RECIST 1.1"}

Exclusion criteria

• {"criterion_text":"- Partial response achieved under first-line immunotherapy-based combination"}
• {"criterion_text":"- Has a systemic infection or other serious infection requiring systemic treatment within 30 days prior to screening"}
• {"criterion_text":"- Has a history of hypersensitivity to EXL01 and/or any excipients, which are listed in the IB, and/or to soybean or soy-containing products"}
• {"criterion_text":"- CTCAE Grade ≥3 or more toxicity under first-line immunotherapy-based combination or persistent toxicity Grade >1"}
• {"criterion_text":"- Liver involvement > 50%"}
• {"criterion_text":"- Presence of major macro vascular invasion (except Vp1/Vp2)"}
• {"criterion_text":"- Pregnant woman, or breastfeeding or women of child-bearing potential with no adequate contraception"}
• {"criterion_text":"- Under curatorship, guardianship, safeguard of justice or deprived of liberty"}
• {"criterion_text":"- History of serious autoimmune disease"}
• {"criterion_text":"- Specific contra-indication to atezolizumab-bevacizumab: 1) Thromboembolic events in the 3 months prior to inclusion 2) Prior bleeding event due to untreated or incompletely treated esophageal and / or gastric varices within 6 months’ prior inclusion 3) Has a history of hypersensitivity to the atezolizumab or to any of the excipients listed in section 6.1 of the SmPC of atezolizumab and bevacizumab or to any of the excipients listed in section 6.1 of the SmPC 4) Uncontrolled hypertension 5) Clinically significant cardiovascular disease such as pre-existing coronary artery disease, or congestive heart failure 6) Proteinuria"}
• {"criterion_text":"- specific contra-indication for durvalumab : Has a history of hypersensitivity to the durvalumab or to any of the excipients listed in section 6.1 of the SmPC of durvalumab"}
• {"criterion_text":"- Interstitial lung disease"}
• {"criterion_text":"- HBV chronic infection with HBV DNA > 100 IU/mL or without antiviral therapy; HBV patients with cirrhosis should be treated"}
• {"criterion_text":"- HIV infection"}
• {"criterion_text":"- Immunosuppression, including subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalent)"}
• {"criterion_text":"- Transplanted liver, or patient with intent for transplantation"}
• {"criterion_text":"- Has difficulties in swallowing."}
• {"criterion_text":"- Has undergone major surgery or significant trauma ≤4 weeks prior to Screening"}
• {"criterion_text":"- Is currently participating in or has participated in a study with an investigational compound or device within 3 months prior to the first dose of study intervention."}

Primary endpoints

• {"endpoint_text":"- The Objective Response Rate at W12, defined as the proportion of patients with a Complete objective tumor Response (CR) or a Partial objective tumor Response (PR) from inclusion to week 12. The objective tumor response is defined as the best overall tumor response (BOR) observed in a patient within all-time points between inclusion to the W12 visit, according to the RECIST 1.1.","definition_or_measurement_approach":"Defined as the proportion of patients with a Complete objective tumor Response (CR) or a Partial objective tumor Response (PR) from inclusion to week 12; objective tumor response = best overall tumor response (BOR) observed between inclusion and W12, assessed according to RECIST 1.1."}
• {"endpoint_text":"- The overall tumor response observed at first imaging after 2 cycles of standard of care immunotherapy (W6 for patients treated with atezolizumab-bevacizumab cohort or W8 for patients treated with durvalumab- tremelimumab cohort), W12, M6, M12 according to the mRECIST, RECIST 1.1 and iRECIST criteria.","definition_or_measurement_approach":"Overall tumor response assessed at first imaging after 2 cycles (W6 for atezolizumab-bevacizumab cohort; W8 for durvalumab-tremelimumab cohort), and at W12, M6, M12 using mRECIST, RECIST 1.1 and iRECIST criteria."}
• {"endpoint_text":"- The ORR at W12, according to the mRECIST, and iRECIST criteria.","definition_or_measurement_approach":"Objective response rate at week 12 assessed according to mRECIST and iRECIST criteria."}
• {"endpoint_text":"- The Disease control rate (DCR), as the proportion of patients with BOR as CR, PR or stable disease (SD) defined according to the mRECIST, RECIST 1.1 and iRECIST criteria at W12, M6, M12.","definition_or_measurement_approach":"DCR = proportion of patients with BOR = CR, PR or SD, assessed by mRECIST, RECIST 1.1 and iRECIST at W12, M6 and M12."}
• {"endpoint_text":"- The Progression-Free Survival, defined as the time from patient inclusion to progression or death from any cause.","definition_or_measurement_approach":"PFS measured as time from inclusion to documented progression or death from any cause."}
• {"endpoint_text":"- The Overall Survival, defined as the time from patient inclusion to death from any cause.","definition_or_measurement_approach":"OS measured as time from inclusion to death from any cause."}
• {"endpoint_text":"- The ORR at M6, M12, according to the mRECIST, RECIST 1.1 and iRECIST criteria.","definition_or_measurement_approach":"ORR assessed at months 6 and 12 using mRECIST, RECIST 1.1 and iRECIST criteria."}

Secondary endpoints

• {"endpoint_text":"- Frequency of adverse events, graded according to the last up-to-date NCI-CTCAE classification. Adverse events are monitored from inclusion to 30 days after the last EXL01 intake.","definition_or_measurement_approach":"Adverse events frequency graded per latest NCI-CTCAE; monitoring period from inclusion to 30 days after last EXL01 intake."}

France

Earliest CTIS Part Ii Submission Date

13-05-2024

Latest Decision Or Authorization Date

22-12-2025

Processing Time Days

588

Number Of Sites

6

Number Of Participants

34

Primary sponsor

Full Name

Centre De Lutte Contre Le Cancer Eugene Marquis

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France