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

NCT07036380 | Recruiting Phase 2 DMC

• 2 other identifiers: 2024/9262024-520029-35-00
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 11

Brief Summary

In the present TACTIC clinical trial, the investigators propose to determine the clinical interest and immunological efficacy of a treatment combining MP0317 the FAP (Fibroblast Activation Protein)-dependent CD40 agonist, with anti-PD-L1(Programmed Death-Ligand 1) therapy (durvalumab) and gemcitabine-cisplatin-based chemotherapy in unresectable cholangiocarcinoma. The main objective is to assess the 12-month progression free survival (PFS) rate in the experimental arm. The trial proposed is a non-comparative proof of concept randomized two-stage phase II. The control arm will serve to verify the good calibration of the null hypothesis made in the experimental arm and to provide "true" controls for translational investigations. A semi-continuous monitoring of toxicity is planned in the experimental arm during the first stage of the study to warrant the tolerability of the experimental treatment and then to guarantee the security of the patients. 75 patients (50 in the experimental arm) will be included. The investigators will also decipher, as a translational objective, the molecular and immunological parameters determining the clinical outcomes.

Conditions

Advanced Biliary Tract Carcinoma

Keywords

immunotherapy; DARPin; Advanced Biliary Tract Carcinoma

Outcome Measures

Primary Outcomes (1)

• progression free survival status (PFS) at 12 months

  12 months

Study Arms (2)

MP0317 + Gemcitabine + Cisplatin + Durvalumab

EXPERIMENTAL

MP0317- Gemcitabine+ Cisplatin + Durvalumab

Drug: MP0317 + Gemcitabine + Cisplatine + Durvalumab; Procedure: CT-Scan

Gemcitabine + Cisplatin + Durvalumab

ACTIVE COMPARATOR

Gemcitabine + Cisplatin + Durvalumab

Procedure: CT-Scan; Drug: Gemcitabine + Cisplatin + Durvalumab

Interventions

CT-Scan PROCEDURE

at baseline, every 6 weeks (± 1 week) for the first 24 weeks and then every 8 weeks until progression, at end of treatment visit, At each follow-up visit : Only for patients who have not progressed during treatment phase

Gemcitabine + Cisplatin + Durvalumab; MP0317 + Gemcitabine + Cisplatin + Durvalumab

Gemcitabine + Cisplatin + Durvalumab DRUG

* Immuno-chemotherapy (ICT) for 8 cycles : * Durvalumab 1500 mg IV, day 1 every 3 weeks * Gemcitabine 1000 mg/m² IV, days 1 and 8 every 3 weeks * Cisplatin 25 mg/m² IV, days 1 and 8 every 3 weeks * Then durvalumab (1500 mg IV) will be administrated in monotherapy maintenance every 4 weeks until progression or unacceptable toxicity.

Gemcitabine + Cisplatin + Durvalumab

MP0317 + Gemcitabine + Cisplatine + Durvalumab DRUG

* MP0317: 3 mg/kg IV(intraveinous), day 1, every 3 weeks for a maximum of 5 administrations * Immuno-chemotherapy (ICT): cycle 1-5 * Durvalumab 1500 mg IV, day 8 every 3 weeks * Gemcitabine 1000 mg/m² IV, days 8 and 15 every 3 weeks * Cisplatin 25 mg/m² IV, days 8 and 15 every 3 weeks * Immuno-chemotherapy (ICT): cycle 6-8 * Durvalumab 1500 mg IV every 3 weeks * Gemcitabine 1000 mg/m² at day 1, 8 every 21 days * Cisplatin 25 mg/m² at day 1, 8 every 21 days * Then durvalumab (1500 mg IV) will be administrated in monotherapy maintenance every 4 weeks until progression or unacceptable toxicity.

MP0317 + Gemcitabine + Cisplatin + Durvalumab

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent
• Histologically confirmed biliary tract carcinoma: intra/extrahepatic cholangiocarcinoma (note that gallbladder carcinoma are not eligible)
• Locally advanced unresectable or metastatic
• 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)
• Age ≥ 18 years
• 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.
• 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 ECOG-PS \< 2 (Eastern Cooperative Oncology Group)
• 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:
• Post-menopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.
• 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.
• Women with documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• 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.
• Documented virology status of hepatitis, as confirmed by screening HBV and HCV tests:
• 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)

You may not qualify if:

• 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
• Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
• Patient under guardianship, curatorship or under the protection of justice
• Other liver malignancy: hepatocellular carcinoma and hepato-cholangiocarcinoma
• Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula
• Known active central nervous system metastases and/or carcinomatous meningitis.
• History of angiocholitis, liver abscess, or acute pancreatitis within 4 weeks prior to initiation of study treatment
• 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).
• HIV (human immunodeficiency virus) positive (HIV 1/2 antibodies patients), or a known history of active Tuberculosis bacillus
• Any immunosuppressive therapy (i.e. corticosteroids \>10 mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy
• 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:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
• 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,

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead
• Molecular Partners AG: collaborator

Study Sites (11)

CHU de Besançon

Besançon, France

RECRUITING

Centre georges-François Leclerc

Dijon, France

RECRUITING

CHU de Grenoble

Grenoble, France

NOT YET RECRUITING

Centre Léon Bérard

Lyon, France

NOT YET RECRUITING

CHU de Montpellier

Montpellier, France

RECRUITING

Hôpital Beaujon

Paris, France

RECRUITING

Hôpital La Pitié-Salpétrière

Paris, France

NOT YET RECRUITING

Institut Curie

Paris, France

NOT YET RECRUITING

Centre Eugène Marquis

Rennes, France

NOT YET RECRUITING

CHU de Tours

Tours, France

RECRUITING

Institut Gustave Roussy

Villejuif, France

NOT YET RECRUITING

MeSH Terms

Interventions

Gemcitabine; durvalumab; Cisplatin

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Christophe BORG

  CHU Besançon

  STUDY DIRECTOR

Central Study Contacts

Christophe BORG, Pr

CONTACT

00 33 3 70 63 22 19; xtoph.borg@gmail.com

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: January 15, 2025
• First Posted: June 25, 2025
• Study Start: December 22, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)