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

NCT07437287 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: UC-GIG-2519
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 22

Brief Summary

The goal of this clinical trial is to etablish whether adding Mitazalimab to standard chemotherapy is more effective than standard chemotherapy alone in people with advanced bile duct cancer. It will also learn about the safety of Mitazalimab. The main questions it aims to answer are:

• Does the addition of Mitazalimab enhance efficacy?
• What medical problems do participants have when taking Mitazalimab + mFOLFOX? Participants will:
• Take drug mFOLFOX every two weeks until disease progression or mFOLFOX every two weeks plus mitazalimab in addition to mFOLFOX, with a first injection 7 days before the first mFOLFOX chemotherapy and then 3 days after the start of each mFOLFOX cycle.
• Visit the clinic once every 2 weeks for checkups and tests
• Have a radiological assessment every 8 weeks during treatment. After stopping treatment, participants will be monitored at the hospital every 8 weeks if no progression is observed, or every 12 weeks after disease progression.

Conditions

Biliary Tract Cancer (BTC)

Keywords

Biliary Tract Cancer; Mitazalimab; Resistance to immunotherapy

Outcome Measures

Primary Outcomes (1)

• 6 months overall survival rate of participants

  Proportion of participant still alive 6 months after randomisation

  From randomisation to 6 months after randomisation

Secondary Outcomes (9)

• Safety of the treatments

  From inclusion to completion of the study, up to 64 months

• Objective response rate of participants (ORR)

  Time from randomisation to disease progression, up to 64 months

• Disease control rate (DCR)

  Time from randomisation to disease progression, up to 64 months

• Progression-free survival (PFS)

  Time from randomisation to disease progression or death, up to 64 months

• Duration of overall response (DOR)

  Time from randomisation to disease progression or death, up to 64 months

Study Arms (2)

Mitazalimab + mFOLFOX

EXPERIMENTAL

Drug: mFOLFOX regimen; Drug: Mitazalimab

mFOLFOX

ACTIVE COMPARATOR

Drug: mFOLFOX regimen

Interventions

mFOLFOX regimen DRUG

oxaliplatin 85 mg/m² intravenous infusion (IV), folinic acid 400 mg/m² IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m² as a 46-hours continuous IV infusion: * every two week (14-day cycles) until disease progression on control arm * at D8 the first cycle and at D1 for subsequent cycles (14-day cycles) until disease progression on experimental arm

Also known as: Oxaliplatin, folinic acid and 5-FU

Mitazalimab + mFOLFOX; mFOLFOX

Mitazalimab DRUG

The first cycle of treatment (21-day cycle): Mitazalimab 900 µg/kg by intravenous infusion (IV) at D1 and D10 Subsequent cycles (14-day cycles): Mitazalimab 900 µg/kg by intravenous infusion (IV) at D3 of each cycle until disease progression

Also known as: ADC-1013, JNJ-64457107

Mitazalimab + mFOLFOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Histologically-proven intrahepatic cholangiocarcinoma, extrahepatic (perihilar/distal) cholangiocarcinoma, or gallbladder carcinoma (ampullary carcinoma excluded)
• Measurable tumor according to RECIST v1.1 classification
• Non-resectable or metastatic disease or recurrent after surgery (if recurrence more than 6 months after adjuvant treatment stop)
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• 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)
• No dihydropyrimidine dehydrogenase deficiency, as assessed by pre-treatment uracil blood level ≤ 16 ng/mL
• Women of childbearing potential must have a negative serum or urine pregnancy test done within 7 days before randomization.
• 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.

You may not qualify if:

• Participants having received previous treatment with fluoropyrimidine, oxaliplatin or CD40 agonist, except for capecitabine given as adjuvant treatment (if last administered \> 6 months).
• Concurrent malignancy (other than BTC), with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 3 years or more and are deemed at negligible risk for recurrence, are eligible for the trial
• Known CNS metastases or carcinomatous meningitis
• History of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
• History of myocardial infarction within 12 months of the first administration of mitazalimab, uncontrolled angina pectoris, unstable cardiac arrhythmias, or congestive heart failure of New York Heart Association class II or greater
• QTc \>450 msec
• Known history of HIV, hepatitis B or active hepatitis C infection
• Toxicities from first-line treatment not resolved to Grade ≤ 1 (according to NCI-CTCAE v6.0) before randomization with the exception of alopecia
• Contraindication to mitazalimab or to FOLFOX regimen, or their excipients
• Prior toxicities of grade ≥ 3 with durvalumab or pembrolizumab (except from vitiligo, alopecia, hypothyroidism, adrenal insufficiency and diabetes) or other immune-related toxicities that led to definitive discontinuation
• Has received attenuated vaccine within 28 days before the first dose of study treatment
• Any condition which in the Investigator's opinion makes it undesirable for the participant to participate in the trial or which would jeopardize compliance with the protocol (including uncontrolled comorbidities, active infections or untreated central nervous system metastases)
• Participation in another therapeutic trial within the 30 days prior to randomization
• Pregnant women or women who are breast-feeding
• Participant unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons

Sponsors & Collaborators

• UNICANCER: lead
• Alligator Bioscience AB: collaborator

Study Sites (22)

Institut de cancérologie de l'Ouest - Site Paul Papin

Angers, 49933, France

Location

CHU de Bordeaux - Hopital Haut Leveque

Bordeaux, France

Location

CHU Brest

Brest, France

Location

Centre François Baclesse

Caen, France

Location

CHU Estaing

Clermont-Ferrand, France

Location

CHU de Dijon

Dijon, France

Location

CHU Grenoble Alpes

Grenoble, France

Location

CHU Lille

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

CHU de Lyon

Lyon, France

Location

APHM - CHU La Timone

Marseille, France

Location

CHU Montpellier - Hôpital Saint Eloi

Montpellier, France

Location

CHU Hotel Dieu

Nantes, France

Location

Hopital du Confluent

Nantes, France

Location

APHP - Hopital Beaujon

Paris, France

Location

Institut Curie

Paris, France

Location

CHU Poitiers

Poitiers, France

Location

Institut Jean Godinot

Reims, France

Location

Centre Eugène Marquis

Rennes, France

Location

Centre Paul Strauss

Strasbourg, France

Location

CHU Tours

Tours, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Oxaliplatin; Leucovorin; Fluorouracil; mitazalimab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Cindy NEUZILLET

  Institut Curie

  PRINCIPAL INVESTIGATOR

• Matthieu DELAYE

  Institut Curie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicolas DE SOUSA CARVALHO

CONTACT

+33 (0)1 71 93 67 09; n-de-sousa@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2026
• First Posted: February 27, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): October 1, 2031
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (22)