Evaluation of the Interest to Combine a CD4 Th1-inducer Cancer Vaccine Derived From Telomerase and Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
The TERTIO trial will propose to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with anti-PD-L1 therapy (atezolizumab) and bevacizumab in unresectable HCC by evaluation of the objective response rate at 6 months (randomized phase II, 10 centers, 105 patients)

Official Title
-----------------
Evaluation of the Interest to Combine a CD4 Th1-inducer Cancer Vaccine Derived From Telomerase and Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: a Proof of Concept Randomized Phase II Study (TERTIO - Prodige 82)

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Drug: Atezolizumab
* Drug: Bevacizumab
* Drug: UCPVax


Participation Criteria
=================
Eligibility Criteria
-----------------
Main inclusion Criteria: Signed informed consent Histologically confirmed hepatocellular carcinoma Locally advanced, metastatic, or unresectable disease Patient who had not previously received systemic anti-cancer treatment Age ≥ 18 years Measurable disease defined according to RECIST v1.1 guidelines (Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.) Patients who have received previous chemoembolization, radioembolization and/or radiotherapy should have recovered from any treatment related toxicity, to a level of ≤ grade 1 (according to National Cancer Institute [NCI] common terminology criteria for adverse events, version 5 (CTCAE v5) with the exception of Grade 2 alopecia Performance status < 2 Child-Pugh Class A status BCLC C stage or BCLC B stage not eligible to loco-regional therapy according to the Barcelona Clinic Liver Cancer (BCLC) staging system Main exclusion Criteria: Non-eligible to a clinical trial: Patients previously exposed to anti-tumor immunotherapy as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy. Diagnosis of additional malignancy within 3 years prior to the inclusion with the exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study Current participation in a study of an investigational agent or in the period of exclusion Patient under guardianship, curatorship or under the protection of justice Cancer-specific exclusion criteria: Know fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula Uncontrolled tumor-related pain: exposing patients to risk of exposure to corticoids or iterative hospitalizations. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to inclusion. Patients should be recovered from the effects of radiation. There is no required minimum recovery period Known active central nervous system metastases and/or carcinomatous meningitis. Subject with previously treated brain metastases and with radiological and clinical stability are allowed Non-eligible to treatment: History of encephalopathy Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization Inadequate organ functions: known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm (Arm A)<br>Atezolizumab + Bevacizumab + UCPVax | Drug: Atezolizumab<br>* 1200 mg IV every 3 weeks until disease progression or unacceptable toxicity<br>Drug: Bevacizumab<br>* 15 mg/kg IV every 3 weeks until disease progression or unacceptable toxicity<br>Drug: UCPVax<br>* UCPVax vaccine (combined with Montanide ISA51 as adjuvant) at 0.5 mg subcutaneously<br>|
| Other: Control Arm (Arm B)<br>Atezoliumab + Bevacizumab | Drug: Atezolizumab<br>* 1200 mg IV every 3 weeks until disease progression or unacceptable toxicity<br>Drug: Bevacizumab<br>* 15 mg/kg IV every 3 weeks until disease progression or unacceptable toxicity<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate (ORR) | addition of complete response (CR) and partial response (PR) rates, evaluated by RECIST criteria v1.1 | at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) | delay from the date of randomization to death from any cause. | through study completion, an average of 2 years | 
| progression-free-survival (PFS) | delay from the date of randomization to the disease progression or death from any cause whichever occurs first | through study completion, an average of 2 years | 
| disease control rate (DCR) | addition of complete response (CR), partial response (PR), and stable disease (SD) rates, evaluated by RECIST criteria v1.1 and imRECIST | at 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CD4 Th1-inducer cancer vaccine