Tactic : MP0317, a Tumor Targeting Fap Dependent CD40 Agonist Darpin, in Combination with Chemoimmunotherapy in First Line Treatment for Patients with Advanced Biliary Tract Carcinoma a Randomized Non Comparative Proof of Concept Phase Ii Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Universitaire

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Nov 2025 → ongoing

Decision date (initial)

2025-09-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the efficacy of a strategy combining MP0317 and durvalumab plus gemcitabine/cisplatin (experimental arm) in terms of progression free rate at 12 months according to RECIST v1.1.

Secondary objectives 11

1. To evaluate the tolerability of Durvalumab, cisplatin/gemcitabine ± MP0317 (experimental arm) during the first step of the primary objective with a semi continuous monitoring of toxicity
2. To assess in the control arm the progression free rate at 12 months according to RECIST v1.1 (annex 2)
3. To assess the progression free survival according to RECIST v1.1, in both arms
4. To assess the overall survival in both arms
5. To investigate the disease control and objective response rates, according to RECIST v1.1 in both arms
6. To assess patient’s Health related Quality of Life (HrQoL) in both arms
7. To evaluate the overall tolerance in both arms
8. To assess biomarkers predictive value for treatment efficacy at baseline
9. To evaluate the association of treatment on blood immune contexture (myeloid, dendritic, B and T cell subsets before and after treatment) in peripheral blood mononuclear cells (PBMC)
10. To investigate the association of treatment on infiltration of lesions by tumor immune cells and PD-L1
11. To characterize the predictive value of soluble biomarkers on treatment response (soluble chemokine, GDF15, CD40, as well as angiogenic and stroma related biomarkers) and nutritional status (inflammatory biomarkers and assessment of sarcopenia)

Conditions and MedDRA coding

ADVANCED BILIARY TRACT CARCINOMA

Study design 2 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Signed and dated informed consent
2. Histologically confirmed biliary tract carcinoma: intra/extrahepatic cholangiocarcinoma (note that gallbladder carcinoma are not eligible)
3. Locally advanced, metastatic, or unresectable disease
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 guidelines (Annex 2) 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) (Annex 5); with the exception of Grade 2 alopecia
8. Performance status ECOG-PS < 2
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, or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening
10. Documented virology status of hepatitis, as confirmed by screening HBV and HCV tests
11. Patient affiliated to or beneficiary of French social security system
12. Ability to comply with the study protocol, in the Investigator’s judgment

Exclusion criteria 23

1. Patients previously exposed to anti-tumor immunotherapy such as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy
2. Known active central nervous system metastases and/or carcinomatous meningitis
3. History of angiocholitis, liver abscess, or acute pancreatitis within 4 weeks prior to initiation of study treatment
4. 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
5. Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
6. Current participation in a study of an investigational agent or in the period of exclusion
7. Patient under guardianship, curatorship or under the protection of justice
8. Other liver malignancy: hepatocellular carcinoma and hepato-cholangiocarcinoma
9. Cholangiocarcinoma displaying IDH1 mutations, FGFR2 fusions, BRAF mutations or HER2 amplification
10. Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula
11. 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
12. 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%.
13. HIV positive (HIV 1/2 antibodies patients), or a known history of active Tuberculosis bacillus
14. Any immunosuppressive therapy (i.e. corticosteroids >10 mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy
15. Active autoimmune disease that has required a systemic treatment in the past 2 years (i.e. corticosteroids or immunosuppressive drugs).
16. Prior allogeneic bone marrow transplantation or prior solid organ transplantation
17. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
18. Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of durvalumab
19. 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
20. 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).
21. Inadequate hepatic function: bilirubin >2 fold ULN, AST/ALT >3 fold ULN, International normalized thromboplastin time ratio >2
22. Creatinine clearance (CrCl) < 60 ml/min (by the Modification of Diet in Renal Disease [MDRD], Cockroft formula, or chronic kidney disease [CKD] formula])
23. Serum albumin < 28 g/L

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the progression free survival status (PFS) at 12 months from the date of randomization evaluated by RECIST criteria v1.1.

Secondary endpoints 11

1. Dose limiting toxicity (DLT) evaluated with NCI-CTCAE criteria
2. Progression free survival status (PFS) at 12 months from the date of randomization evaluated by RECIST criteria v1.1.
3. The PFS evaluated by RECIST criteria v1.1. Progression-free survival (PFS): defined as the delay from the date of randomization to the disease progression or death from any cause whichever occurs first. Alive patient without progression will be censored at last radiological evaluation available showing no progression.
4. Overall survival (OS): defined as the delay from the date of randomization to death from any cause. Alive patient will be censored at last date known to be alive.
5. Objective Response Rate (ORR): defined as the addition of complete response (CR) and partial response (PR) rates, evaluated by RECIST criteria v1.1. Disease control rate (DCR): defined as the addition of complete response (CR), partial response (PR), and stable disease (SD) rates, evaluated by RECIST criteria v1.1
6. Health related quality of life: EORTC-QLQ-C30 + EORTC QLQ – BIL21
7. Toxicities graded according to NCI-CTCAE criteria version 5
8. Tumor related biomarkers
9. On PBMC
10. - PD-L1/FAP/CD40 expression on tumor and immune cells will be determined by immunohistochemistry at baseline, as well as presence of Tertiary lymphoid structures (CD3/CD8/CD20 and CD68/SSP1/CXCL9)
11. On the serum: - Anti-drug antibodies (ADA) - Monitor the concentration of MP0317 drug (PK) in serum

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire

Sponsor organisation

Centre Hospitalier Regional Universitaire

Address

2 Place Saint Jacques, Cs 51804 Cs 51804

City

Besancon Cedex

Postcode

25030

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire

Contact name

REBUCCI-PEIXOTO

Public contact point

Organisation

Centre Hospitalier Regional Universitaire

Contact name

DEPIERRE

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications