MP0317 in Combination With Chemoimmunotherapy in First Line Treatment for Patients With Advanced Biliary Tract Carcinoma

Exclusion Criteria

• •3. Locally advanced unresectable or metastatic
• •4. Patient who had not previously received systemic anti-cancer treatment (adjuvant treatment with Capecitabine is allowed if the end of the chemotherapy was at least 6 months ago)
• •5. Age ≥ 18 years
• •6. Measurable disease defined according to RECIST v1.1 (Response Evaluation Criteria In Solid Tumours) guidelines Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.
• •7. 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
• •8. Performance status ECOG-PS \< 2 (Eastern Cooperative Oncology Group)
• •9. Females must be using highly effective contraceptive measures, and have a negative pregnancy test prior to the start of dosing if of childbearing potential, and during treatment and at least 7 months after the end of the treatment with cisplatin, 6 months after the end of the treatment with gemcitabine, 3 months after the end of the treatment with durvalumab, or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
• •1. Post-menopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.
• •2. Women under the age of 50 years would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution.
• •3. Women with documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• •4. Male patients with a female partner of childbearing potential should be willing to use barrier contraception during the study and at least: 4 months after the end of the treatment with cisplatin and 3 months after the end of the treatment with gemcitabine. Patients should refrain from donating sperm from the start of dosing until 4 months after discontinuing study treatment.
• •10. Documented virology status of hepatitis, as confirmed by screening HBV and HCV tests:
• •1. For patients with active HBV: HBV DNA \<500 IU/ml (International unit)during screening, initiation of anti-HBV treatment at least 14 days prior to randomization and willingness to continue anti-HBV treatment during the study (per local standard of care; e.g., entecavir)
• •2. Patients with HCV, either with resolved infection (as evidenced by detectable antibody) or chronic infection (as evidence by detectable HCV RNA), are eligible
• •11. Patient affiliated to or beneficiary of French social security system
• •12. Ability to comply with the study protocol, in the Investigator's judgment.
• •For patients whose tumors present a genetic alteration of IDH1, FGFR2 or BRAF as well as an amplification of HER2, the investigators of the TACTIC study recommend, if possible, the orientation for preferential inclusion in the SAFIR ABC10 study".
• •1. Patients previously exposed to anti-tumor immunotherapy such as anti-PD-1, anti-PD-L1, or anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) agent or any immune therapy
• •2. 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
• •3. Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
• •4. Current participation in a study of an investigational agent or in the period of exclusion
• •5. Patient under guardianship, curatorship or under the protection of justice
• •6. Other liver malignancy: hepatocellular carcinoma and hepato-cholangiocarcinoma
• •7. Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula
• •8. 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
• •9. Known active central nervous system metastases and/or carcinomatous meningitis.
• •10. History of angiocholitis, liver abscess, or acute pancreatitis within 4 weeks prior to initiation of study treatment
• •11. Inadequate organ functions: known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition. Patients requiring oxygen therapy or with LEVF\<40% (Left ventricular ejection fraction).
• •12. HIV (human immunodeficiency virus) positive (HIV 1/2 antibodies patients), or a known history of active Tuberculosis bacillus
• •13. Any immunosuppressive therapy (i.e. corticosteroids \>10 mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy
• •14. Active autoimmune disease that has required a systemic treatment in the past 2 years (i.e. corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin) is allowed. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• •1. Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study
• •2. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
• •3. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• •* Rash must cover \< 10% of body surface area,
• •* Disease is well controlled at baseline and requires only low-potency topical corticosteroids,
• •* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months,
• •15. Prior allogeneic bone marrow transplantation or prior solid organ transplantation
• •16. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• •17. Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of durvalumab
• •18. Receipt of a live, attenuated vaccine within 30 days prior to inclusion or anticipation that such a live, attenuated vaccine will be required during the study Note: Patients must agree not to receive live, attenuated influenza vaccine within 28 days prior to randomization, during treatment or within 5 months following the last dose of durvalumab
• •19. Inadequate hematology function: Lymphocyte count at baseline \< 700/mm3; neutrophil count \< 1 500/mm3, platelets \< 10 0000/mm3 (without transfusion), Hemoglobin \< 9g/dL (patients may be transfused to meet this criterion).
• •20. Inadequate hepatic function: bilirubin \>2 fold ULN (upper limit of normal), AST/ALT \>3 fold ULN, International normalized thromboplastin time ratio \>2
• •21. Creatinine clearance (CrCl) \< 60 ml/min (by the Modification of Diet in Renal Disease \[MDRD\], Cockroft formula, or chronic kidney disease \[CKD\] formula\])
• •22. Serum albumin \< 28 g/L
• •23. Surgery within 4 weeks previously the initiation of the study treatment
• •24. Radiotherapy within 2 weeks previously the initiation of the study treatment
• •25. Patient with weight \< 36 kg.
• •26. Pregnant or breastfeeding woman
• •27. Known hypersensitivity to components of MP0317, for exemple, histidine buffer or the Tween diluent, according to section 7.2 " Contraindications " of the Investigator's brochure of MP0317
• •28. Hypersensitivity to gemcitabine or to cisplatin, or to any of their excipients, according to the SmPCs of these products
• •29. According to the SmPC of cisplatin: hearing problem, in case of combination with phenytoin with prophylactic aim, patients with neuropathy caused by cisplatin, in case of cardiorespiratory pathology in particular, which forbids a hyperhydration