PEHRICCA : PErioperative CISGEM plus RILVEGOSTOMIG in High-Risk resectable Intrahepatic CholangioCarcinoma

Prior treatment

• Live vaccine administration within 30 days prior to the first dose of study treatment Note: Patients, if enrolled, should not receive live vaccine whilst receiving investigational product and up to 6 months after the last dose of investigational product
• History of clinically significant arrhythmia, cardiomyopathy of any etiology; symptomatic congestive heart failure (as defined by New York Heart Association class ≥ 3), history of myocardial infarction within the past 6 months. Participation in another clinical study with an investigational product during the last 4 weeks
• Contraindication to immunotherapy: Active or prior documented autoimmune or inflammatory disorders or any severe or uncontrolled systemic disease
• Current or prior use of immunosuppressive medication within 14 days before the first dose

Other illness

• Active and untreated infection with hepatitis B and/or hepatitis C Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive hepatitis B core antigen [HBc] antibody test) are eligible.
• Other active cancer or history of cancer within 2 years, except for carcinoma in situ of the cervix or basal cell or squamous cell skin carcinoma or any other carcinoma in situ, considered cured
• Locally advanced disease considered as definitively non resectable
• Persistent toxicities (>CTCAE grade 2) caused by previous cancer therapy, excluding alopecia.
• History of allogenic organ transplantation
• Known or suspected allergy or hypersensitivity to any of the study drugs or any of the study drug excipients (cisplatin, gemcitabine and Rilvegostomig)

Lab values

• Uncontrolled infection with human immunodeficiency virus (HIV). Required conditions for inclusion are as follows: undetectable viral RNA, CD4+ count ≥350 cells/μL, no history of AIDS-defining opportunistic infection within the past 12 months, stable condition for at least 4 weeks on the same anti-HIV medications.
• Cirrhosis with Child ≥ B7 a. Any history of liver decompensation: hepatic encephalopathy, presence of ascites b. Presence of clinically significant portal hypertension (platelets counts < 150G/L and/or liver stiffness > 20kPa and/or presence of oesophageal and/or gastric varices)

Other

• Existence of metastases or distant lymph node involvement considered as metastatic
• Pregnant or breastfeeding woman
• Persons deprived of liberty or under guardianship or incapable of giving consent
• Inability to undergo the medical follow-up of the trial for geographical, social or psychological reasons
• Mixed histology (hepatocholangiocarcinoma)

• Age ≥ 18 years
• Life expectancy ≥ 3 months
• Female Patients postmenopausal for at least one year or surgically infertile for at least 6 weeks, or highly effective contraception for male and female patients of childbearing potential for the duration of study and for 7 months after the last dose of drug for female and 4 months for male.
• A negative pregnancy test for inclusion for all female patients of child-bearing potential
• Patient covered by a plan of the French Social Security system
• Written informed consent obtained from the patient prior to performing any protocol-related procedures
• Patient with available tumor tissue sample for the study or willing to have a biopsy
• WHO PS 0-1
• Body weight > 30kg
• Histo/cytologically proven intrahepatic cholangiocarcinoma
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST 1.1 criteria ».
• Naive to systemic treatment and loco regional treatment for biliary tract cancer
• Resectable disease with at least one of the following high-risk criteria of post resection relapse: • Tumor Size ≥ 50 mm and/or tumor number > ou = 3 nodules (maximum 5, in the same lobe), satellite nodules may be included ((intrahepatic metastases <2 cm at <2 cm from the primary nodule) • cN1 (according to TNM classification 8th edition 2017): hilar, peri duodenal and peri pancreatic adenopathy for iCCA of right liver and hilar, inferior phrenic, gastrohepatic, adenopathy for iCCA of left liver • Risk of R1 margin: distance < 10 mm from major structures, i.e., the right and left glissonian pedicles and/or hepatic veins (to be discussed during a MDT) • Macrovascular invasion (portal vein and/or sus hepatic veins and/or vena cava invasion). • ❖ (Liver MRI with PRIMOVIST contrast injection if possible, and diffusion-weighted sequences)
• Adequate organ function, as defined by the following: • Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 2,5 x Upper Limit of Normal (ULN) • Total serum bilirubin ≤1.5 ULN This will not apply to patients with confirmed Gilbert’s syndrome • Prothrombin ratio > 70% and/or Factor V> 70% in case of oral anticoagulation therapy • Serum albumin ≥ 30 g/L • Haemoglobin ≥ 10 g/dl and no transfusion within 4 weeks before inclusion • Absolute Neutrophil Count (ANC) ≥ 1,500/μL • Platelets ≥ 150,000/μL
• Creatinine clearance ≥45 ml/min (calculated by CKD-EPI)