Testing Mitazalimab in Combination With Standard Chemotherapy in Immunotherapy Resistant Advanced Biliary Tract Cancers

Inclusion Criteria

• •1. Age ≥18 years
• •2. Histologically-proven intrahepatic cholangiocarcinoma, extrahepatic (perihilar/distal) cholangiocarcinoma, or gallbladder carcinoma (ampullary carcinoma excluded)
• •3. Measurable tumor according to RECIST v1.1 classification
• •4. Non-resectable or metastatic disease or recurrent after surgery (if recurrence more than 6 months after adjuvant treatment stop)
• •5. Participants having received a standard first-line treatment (CISGEM + durvalumab or pembrolizumab) and eligible for second- or third-line treatment with FOLFOX. Participant could have received a previous targeted therapy in case of targetable alteration, but only one line of chemotherapy is permitted.
• •6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• •7. Adequate bone marrow reserve, normal renal and liver functions:
• •* Neutrophil count ≥ 1500/mm³
• •* Platelet count ≥ 150 000/mm³
• •* Hemoglobin ≥ 10 g/dl
• •* Estimated glomerular filtration rate (eGFR) value ≥50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
• •* Total bilirubin \< 1.5 x ULN (after biliary stent placement in case of biliary obstruction)
• •8. No dihydropyrimidine dehydrogenase deficiency, as assessed by pre-treatment uracil blood level ≤ 16 ng/mL
• •9. Women of childbearing potential must have a negative serum or urine pregnancy test done within 7 days before randomization.
• •10. Participants must agree to use adequate contraception methods for the duration of study treatment and for within 15 months for women and 12 months for men after completing treatment.
• •11. Participants must be affiliated to a Social Security System (or equivalent).
• •12. Participant must have signed a written informed consent prior to any trial specific procedures. When the participant is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the participant's consent.
• •13. Participants must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.
• •14. Have archival tumor tissue sample that has been identified and confirmed as available
• •15. Participant having consented for a new tumor biopsy at inclusion for ancillary studies (participants with non-contributory new biopsy may still be included in the study).