Biliary Tract Cancer (BTC)

The purpose of this study is to explore the efficacy and safety of Ivonescimab in combination with GEMOX chemotherapy as neoadjuvant and conversion therapy for patients with biliary tract cancer. It aims to evaluate the impact of this combination regimen on postoperative recurrence, patient survival, and medication safety. This is a single-center, phase II, interventional, single-arm, multi-cohort clinical study. A total of 87 eligible participants will be enrolled and assigned to either the neoadjuvant therapy cohort (45 participants) or the conversion therapy cohort (42 participants).

The purpose of this study is to explore the effects of sacituzumab tirumotecan combined with pembrolizumab on survival, disease progression, and safety in patients with advanced biliary tract malignancies in the second-line and later settings. This is a multicenter, phase II, interventional single-arm clinical study. A total of 38 participants will be enrolled. Participants will receive the combination therapy until disease progression or unacceptable toxicity.

This study is designed to 1) select a dose regimen for continued development and 2) evaluate nanvuranlat versus Physicians Best Choice (PBC) (FOLFOX, FOLFIRI, or Best Supportive Care (BSC)) in participants aged 18 years and over with BTC. Participants enrolling in Part A the trial will be randomly assigned to receive 1 of 3 nanvuranlat dose regimens or PBC. In Part B, participants will be randomly assigned to receive nanvuranlat or PBC. Participants will receive treatment every 2 weeks for as long as they do not experience safety issues, or their cancer gets worse, and the study doctor feels they should stop treatment. Health measurements including physical examinations, vital signs, ECGs, and safety laboratory tests will be performed to monitor safety, and tumor imaging will be performed to monitor cancer response to treatment. Other exploratory makers will be measured to better understand how nanvuranlat works.

This is a first-in-human, Phase 1/2, open-label, dose escalation and dose expansion and combination study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of Spevatamig (PT886). Patients with the following tumor types will be eligible for screening: unresectable or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, biliary tract carcinoma (BTC), pancreatic ductal adenocarcinoma (PDAC) and colorectal carcinoma (CRC).

This study will evaluate the efficacy and safety of cryoablation combined with QL1706 (iparomlimab/tuvonralimab) plus lenvatinib in patients with advanced biliary tract cancer (BTC) who have progressed after first-line treatment.

This study is being done to find out whether bile fluid can be used to detect genetic changes in tumors of patients with advanced biliary tract cancer (BTC), such as cancer of the bile ducts or gallbladder. Currently, doctors often use a sample of tumor tissue to look for genetic changes that can help guide treatment decisions, including the use of targeted therapies. However, in biliary tract cancer, it can be difficult or risky to collect enough tumor tissue for this kind of testing. This study will collect a small amount of leftover bile (about 20 mL) during a procedure that patients are already having for medical reasons (such as ERCP or PTBD, which are used to drain bile). A blood sample (about 20 mL) will also be collected at the same time patients are already having blood drawn as part of their regular care. No additional needle sticks or procedures will be done only for this study. Researchers will analyze the genetic material found in the bile and blood samples and compare the results with the genetic testing already done on the patient's tumor tissue. The main goal is to see how closely the genetic changes found in bile match those found in tumor tissue. The study will also look at whether bile testing can detect genetic changes that may help guide treatment, and whether these results are related to how patients respond to treatment and their long-term outcomes. About 100 patients with advanced biliary tract cancer will take part in this study at 4 hospitals in South Korea.

This is a single-arm, multicenter clinical study designed to evaluate the efficacy and safety of Iparomlimab and Toripalimab (QL1706) in combination with bevacizumab and chemotherapy as first-line treatment for patients with advanced biliary tract cancer

This Phase 1, open-label study will evaluate two investigational radiopharmaceuticals in adults with selected advanced or metastatic solid tumors. SKL35502 is an imaging agent used with SPECT scans to identify tumors with neurotensin receptor 1 (NTSR1), a protein found on some cancer cells, and to assess where the agent travels in the body and the radiation dose delivered to tissues. Participants with sufficient SKL35502 tumor uptake may receive SKL35501, a treatment designed to deliver targeted alpha radiation to NTSR1-expressing tumor cells. Part A will evaluate the safety and imaging performance of SKL35502 and the safety, tolerability, pharmacokinetics, biodistribution, dosimetry, and biologically active dose range of SKL35501, as well as preliminary antitumor activity. Part B will further evaluate selected SKL35501 dose levels, including randomized low- and high-dose groups in participants with colorectal cancer, and will expand evaluation in selected tumor types. The study will also examine relationships among SKL35502 imaging, NTSR1 expression, SKL35501 tumor uptake, and treatment outcomes.

This study, the first clinical trial of AVZO-1418, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of AVZO-1418 when administered intravenously as a monotherapy and potentially in combination therapy to patients with locally advanced or metastatic epithelial solid tumors.

This is a prospective, single-arm, phase II clinical study. Patients with advanced cholangiocarcinoma harboring FGFR2 fusions or rearrangements who have either not previously received standard therapy or have experienced treatment failure following standard therapy will be screened for eligibility and enrolled in the study after providing written informed consent.

This study aims to determine the safety and maximum tolerated dose (MTD) of YMN-136 vaccine through a dose escalation trial, and to investigate whether YMN-136 vaccine can assist in the treatment of patients with advanced hepatobiliary and pancreatic malignancies.

The objective of SAFIR-IMPACT BTC is to see whether, combining or replacing the standard adjuvant chemotherapy with a targeted therapy matched to the person's cancer, is better than the standard treatment alone in delaying or preventing the return of the cancer. Three different targeted therapies will be evaluated, each of which recognises a different type of abnormality in cancer cells: * Ivosidenib - a drug which acts on a specific abnormality in a protein called IDH1. * Futibatinib - a drug which acts on abnormalities in a protein called FGFR2 * Zanidatamab - a drug which acts on cancers that produce more than the usual quantity of a protein called HER2. The trial is composed of two phases: (i) An initial screening phase to identify a suitable patient population, during which a sample of the patient's tumour will be tested to see if it has one of the target abnormalities being studied (ii) a randomised comparative phase (for selected patients only) which consists of comparing two treatment options: some patients will receive the targeted therapy specific to the abnormality identified in their tumour, while others will receive the standard treatment. Patients will be assigned to one treatment or the other by a random draw: they will have a 2 in 3 chance of receiving the targeted therapy. Randomised participants will: * Take their assigned treatment for 6 months * Visit the clinic once every 3 weeks for checkups and tests * Keep a diary of their symptoms and the treatment they take at home Follow-up information will be collected for all participants until the end of the trial.

The object of this trial is to evaluate the efficacy of D07001-softgel capsules + capecitabine compared with placebo + capecitabine by overall survival (OS). Eligible patients with advanced biliary tract cancer (BTC) will be randomized (1:1:1) to receive either 60 mg D07001-softgel, 100 mg D07001-softgel, or placebo, combine with capecitabine. Treatment will be continued until disease progression, death, withdraw consent, or completing 12 treatment cycles , whichever occurs first.

This study will evaluate the safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of the IKS04 Regimen and identify a recommended phase 2 dose (RP2D) or recommended dose for further evaluation in expansion (RDE). The regimen includes Isumab04 (unconjugated antibody) followed by the IKS04 antibody-drug conjugate, both directed against the CA242 (CanAg) tumor-associated antigen and administered intravenously (IV) in patients with advanced solid cancers.

The goal of this clinical trial is to evaluate whether QL1706(Iparomlimab/Tuvonralimab) in combination with gemcitabine and cisplatin (GC) is effective and safe as a first-line treatment for patients with advanced biliary tract cancer whose tumors are PD-L1 positive (CPS ≥ 1). This is a multicenter, single-arm, phase II clinical study. A total of 38 eligible patients will be enrolled . The main questions it aims to answer are: what proportion of patients achieve objective response (tumor shrinkage) after receiving QL1706 plus GC, as measured by the objective response rate (ORR)? How long do the treatment benefits last, in terms of disease control rate (DCR), duration of response (DOR), time to response (TTR), progression-free survival (PFS), and overall survival (OS)? What is the safety profile of QL1706 combined with GC, including the frequency and severity of adverse events, treatment-related adverse events, serious adverse events, and immune-related adverse events? Participants will receive QL1706 (5 mg/kg, intravenous infusion) once every 3 weeks in combination with gemcitabine (1000 mg/m² on days 1 and 8) and cisplatin (25 mg/m² on days 1 and 8) for up to 8 cycles (each cycle is 3 weeks), and after completing 8 cycles of combination therapy, they will continue QL1706 alone as maintenance therapy (5 mg/kg once every 3 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, loss to follow-up, death, or completion of 2 years of treatment, whichever occurs first. Participants will undergo tumor imaging assessments (using CT or MRI) every 9 weeks (±7 days) during the treatment period, with responses evaluated . Participants will also have regular blood tests, physical examinations, electrocardiograms, and other safety assessments at each treatment cycle, and will provide tumor tissue and blood samples before treatment and at various time points during the study for biomarker analyses to explore correlations with treatment response. Finally, participants will be followed for adverse events for 30 days after the last dose, for serious adverse events for 90 days after the last dose, and for survival status every 90 days (±14 days) after the end of treatment until death, study completion, or loss to follow-up. The study is expected to provide valuable evidence on whether the addition of QL1706 to standard GC chemotherapy offers a new treatment option for patients with PD-L1-positive advanced biliary tract cancer, and to identify potential biomarkers that may help predict which patients are most likely to benefit from this combination therapy.

This study is a prospective, multicenter, single-arm, open-label Phase II clinical trial, planned to enroll 30 patients with unresectable locally advanced or metastatic iCCA/GBC. Patients will first receive cryoablation treatment, and two weeks after ablation, they will receive 8 cycles of immunotherapy combined with chemotherapy (Relatlimab α plus GC chemotherapy, every 3 weeks). During the maintenance phase, patients will continue with Relatlimab α alone, every 3 weeks, for up to one year. During the combination treatment phase, efficacy will be evaluated every 6 weeks, and during the maintenance phase, every 6 to 9 weeks. From the date of randomization/enrollment, survival follow-ups will be conducted every 3 months (±14 days) for the first 2 years; afterwards, follow-ups will occur every 6 months (±28 days) until the participant dies, is lost to follow-up, or the study ends, whichever comes first.

Biliary tract carcinoma (BTC), including cholangiocarcinoma and gallbladder cancer, is a highly aggressive digestive system malignancy with limited treatment options after failure of first-line standard chemotherapy. This open-label, single-arm, Phase II exploratory study aims to evaluate the efficacy and safety of Becotatug Vedotin combined with Pucotenlimab in patients with EGFR-positive advanced BTC who have failed first-line therapy. Participants will receive the combination regimen until the occurrence of disease progression, unacceptable toxicity, withdrawal of informed consent, death, pregnancy, investigator's decision to discontinue treatment, or study termination, whichever occurs first.The primary endpoint is objective response rate (ORR) assessed per RECIST v1.1. Secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety.

According to current clinical guidelines, first-line treatment for advanced biliary tract cancer (BTC) is the gemcitabine plus cisplatin (GC) regimen combined with immunotherapy, which has been shown to improve patient outcomes. Additionally, the combination of radiotherapy and immunotherapy may synergistically enhance antitumor efficacy. Therefore, this study aims to assess the efficacy and safety of first-line treatment with radiotherapy in combination with sintilimab and gemcitabine/cisplatin versus sintilimab in combination with gemcitabine/cisplatin in patients with previously untreated, unresectable locally advanced or metastatic BTC.

A Phase 1/1B Study of ST-01156 in Patients with Advanced Solid Malignancies

Biliary tract cancer (BTC), including cholangiocarcinoma and gallbladder cancer (GBC), is a group of malignancies with highly heterogeneous, highly aggressiveness, and poor prognosis. Surgery is recognized as the only curative treatment for BTC, however, only about 20% BTC patients are eligible for curative resection since most patients with BTC are diagnosed at an advanced stage. The median overall survival (OS) in patients with unresectable BTC is typically less than 6 months. For patients with unresectable BTC, gemcitabine plus cisplatin (GemCis) had been recommended as the standard first-line treatment for many years. However, the objective response rate (ORR) of this regimen is only 26.1%, and the survival benefit remains limited, with a median OS of less than one year. In recent years, two phase III trials (TOPAZ-1 and KEYNOTE-966) have demonstrated that combining immune checkpoint inhibitors (durvalumab or pembrolizumab) with the GemCis regimen could further prolong survival in patients with BTC, achieving a median OS of 12.9 months and 12.7 months, respectively. Based on this evidence, many guidelines worldwide had recommended GemCis plus durvalumab or pembrolizumab as the preferred standard first-line treatment for patients with unresectable BTC. However, survival benefits from this combination therapy remain relatively limited, and tumor response is suboptimal, with an ORR of only 26.7%-29%. Hepatic arterial infusion chemotherapy (HAIC) enables continuous infusion of chemotherapeutic agents via the hepatic artery, significantly increasing local drug concentration at the tumor site, maximizing antitumor efficacy, and achieving a higher ORR (50%-60%) with substantial reduction in tumor burden. In recent years, HAIC has been increasingly used in the treatment of unresectable BTC, with its efficacy supported by many clinical studies. Firstly, HAIC provides survival benefits comparable to surgery in patients with multifocal intrahepatic cholangiocarcinoma (iCCA), and significantly outperforms systemic therapy. In 2022, a retrospective study enrolled 141 patients who received HAIC and 178 patients who underwent surgical resection from 12 centers. The results showed the median OS was 20.3 months in the HAIC group and 18.9 months in the resection group (P = 0.32), indicating comparable survival outcomes between HAIC and surgery. Given the risks of post-hepatectomy complications, HAIC may serve as an effective alternative treatment strategy for multifocal iCCA. Furthermore, for locally advanced unresectable iCCA, the results in a study in 2024 comparing HAIC with GemCis regimen chemotherapy revealed that although patients in the HAIC group had a higher tumor burden (proportion of multifocal disease: 73.4% vs. 55.3%, P = 0.023), the median OS in HAIC group remained significantly superior to that in the GemCis group (27.7 months vs. 11.8 months, P \< 0.001). Secondly, HAIC has also been demonstrated to be effective in treating perihilar cholangiocarcinoma (pCCA). In 2017, a single-arm, prospective phase II trial conducted in our center showed HAIC with oxaliplatin and fluorouracil yielded an ORR of 67.6%, a median progression-free survival (PFS) of 12.2 months, and a median OS of 20.5 months in treating perihilar cholangiocarcinoma (pCCA). Furthermore, HAIC also has clinical potential in treating advanced GBC. In 2021, a retrospectively study in our center enrolled 26 patients with advanced GBC who received HAIC with oxaliplatin and fluorouracil, of whom 23.1% had failed prior systemic therapy and 34.6% had contraindications to systemic treatment. The results showed that HAIC achieved a median PFS of 10 months and a median OS of 13.5 months, with an ORR of 69.2% and a disease control rate (DCR) of 92.3%. In recent years, many studies have demonstrated that HAIC combined with systemic therapy could yield significant survival benefits in patients with unresectable BTC. A phase II clinical trial in 2022 evaluated the efficacy of HAIC with floxuridine plus systemic gemcitabine and oxaliplatin (GEMOX) in unresectable iCCA. The results showed that the combination therapy achieved a median PFS of 11.8 months and a median OS of 25 months, with a 6-month DCR of 84%, and 58% of patients achieved partial response (PR). Additionally, the association of benefit of combining HAIC with systemic chemotherapy and stage of BTC has been reported, and that patients with locally advanced cholangiocarcinoma may not derive such benefit from this combination. In 2025, a phase II clinical trial conducted in our center evaluated the efficacy and safety of HAIC (bevacizumab, oxaliplatin, and fluorouracil) combined with toripalimab as a first-line treatment for unresectable BTC. The results showed a median PFS of 13.2 months and a median OS of 19 months, with an ORR as high as 84.38%. Some patients achieved successful conversion resection following this combination therapy, and postoperative pathology confirmed pathological complete res

Hepato-Pancreato-Biliary (HPB) cancers originating in the liver, bile ducts, pancreas, and gall bladder represent a rising global health challenge, with incidence doubling in the UK over the past decade. Cholangiocarcinoma (CCA) and pancreatic cancer are particularly aggressive, often detected late due to non-specific symptoms and difficulties in sampling or imaging. In the UK, CCA affects around 3,000 people annually, with only 13% surviving 3 years, while pancreatic cancer has a 5-year survival of 8.3%. Diagnosis is complicated by the anatomical narrowness of the bile duct and the similarity between malignant and benign strictures. Standard imaging often cannot distinguish between inflammation and cancer, while tissue sampling is challenging, paucicellular, and limited in sensitivity, necessitating repeated biopsies. Yet, accurate characterisation is critical as NICE now recommends targeted therapies (FGFR2, NTRK, MSI-H/dMMR, IDH1 mutations) that require molecular profiling. Both CCA and PDAC display high heterogeneity, further complicating treatment. Emerging approaches such as Raman spectroscopy can map malignant tissues by detecting vibrational energy shifts, but require further validation due to weak signals. For focal or cystic HPB lesions not well visualised by conventional imaging, novel modalities like ultra-thin endoscopes with scattering/absorption imaging are being developed for improved early diagnosis. Management of biliary obstruction frequently involves stenting to restore bile flow, essential for palliation and pre-treatment optimization. However, stent failure from tumour ingrowth, displacement, or erosion remains common, and evidence for best stent use is limited. Novel approaches, including drug-eluting coatings and nanoparticle-mediated wireless treatment delivery, are being investigated. To overcome diagnostic and therapeutic barriers, flexible snake-like robotic systems with navigation, sampling, spectroscopy, and treatment capabilities are being developed. These devices, alongside ultra-thin endoscopes and integrated Raman spectroscopy, aim to characterise strictures, generate 3D imaging in ex-vivo HPB tissue, and permit targeted ablation. Parallel work will explore molecular and fluid-based biomarkers (blood, bile, cyst fluid) to support minimally invasive diagnosis and monitoring. Through integration of engineering, molecular diagnostics, and device innovation, this transdisciplinary research programme (UKRI and MRC funded) seeks to transform early detection, accurate diagnosis, and novel treatment of HPB cancers, thereby improving outcomes in CCA, pancreatic malignancy, and other clinically similar biliary disorders. Aim: To provide a detailed understanding of the characteristics (including clinical and molecular) of liver and pancreatic biliary focal lesions (inflammatory and cancerous) and create a bioresource of liver, pancreas, gallbladder and biliary tract associated tissue and fluids (biopsies, brushings, resected tissues, bile and cyst fluid and blood samples) in order to develop innovative tools for accurate diagnosis and treatment. Study Configuration: Prospective Longitudinal Cohort study Setting: Secondary care centre, Nottingham University Hospitals NHS Trust. (NUH). Co-ordinated by the NIHR Nottingham Biomedical Research Centre Description of interventions: This is an observational study involving collecting tissue or body fluids (such as bile or pancreatic cyst fluid) during clinical care in addition to collection of blood samples (for DNA, serum and plasma) and data collection. Surplus tissue residual to the requirements for standard care will be stored and used. Additional tissue samples and body fluid samples collected for research at time of clinical investigations will not be increasing the risk of the clinical procedure. Blood samples will be collected from patients at the time of enrolment in the study. These may be collected before and/ or after diagnosis is secured. Duration of study: Overall duration: 60 months Outcome measures: - To report the proportion of patients where adequate tissue could be retrieved from HPB biopsy to come to definitive diagnosis using standard of care. * To report the proportion of patients where adequate tissue could be retrieved from biopsy to perform molecular characterisation of HPB samples, beyond standard cyto/histology, using advanced optical-spatial technologies currently under development. * To report the proportion of patients where definitive diagnosis of mucinous cystic neoplasm could be made in patients with pancreatic cyst using standard care * To report the proportion of patients where molecular characterisation beyond standard cyto/histology could be made in patients with pancreatic cyst using exploratory new technologies under development through ex-vivo experiments * To report the correlation between Raman Spectroscopy and standard cyto/histology for identification of cancer in HPB samples

The REVEAL-BTC Study will analyze 5 biomarkes in samples of participants who in the past 15 year have been diagnosed with any stage of biliary tract cancer. The expression levels of the biomarkers will be correlated with clinical outcomes in the participants, which will lead to better patient stratification that will help guide the use of targeted therapies in the future.

This is an open label, multi-center, multiple dose Phase 1 study to evaluate the safety, tolerability, MTD PK, and PD of TJ033721 (givastomig) in subjects with advanced or metastatic solid tumors.

Purpose of the Study: Bile duct cancers are rare and aggressive. About 250 new cases are diagnosed each year in Denmark. These cancers are difficult to detect early, so only about 20% of patients can have surgery when diagnosed. Even after surgery, the cancer often returns, and chemotherapy only slightly reduces the risk of relapse. For patients who cannot have surgery, treatments such as chemotherapy (sometimes combined with immunotherapy) can relieve symptoms and extend life, but their effect is limited. A small number of patients have specific genetic changes in their cancer that can be treated with targeted medicines. Currently, doctors cannot predict which patients will benefit from treatment. Standard monitoring methods like CT scans are expensive, inconvenient, and sometimes unreliable because bile ducts are hard to see clearly on scans. Blood tests that detect cancer DNA in the blood (called circulating tumor DNA or ctDNA) and other biological markers may be a better way to monitor the disease and adjust treatment. These tests could help detect cancer recurrence earlier and determine whether treatment is working. Measuring patients' quality of life and symptoms over time may also help predict treatment benefit and evaluate effectiveness. The goal of this study is to: * Investigate how biomarkers, including ctDNA, can predict disease course, detect relapse, and monitor treatment response. * Identify the best way to measure ctDNA in patients with bile duct cancer. * Examine whether patients' own reports of quality of life and symptoms can help assess treatment effect and prognosis. Study Design and Procedures: This is a prospective cohort study focusing on blood biomarkers and patient-reported symptoms and quality of life. Participants agree to provide blood samples: * Before treatment * During treatment * During follow-up Each sample involves up to 40 ml of blood, with a maximum of 20 samples per patient. The blood will be analyzed for: * ctDNA and genetic changes * Cancer-related markers * Inflammation markers * Immune system markers Tumor tissue samples will also be examined to compare blood and tissue results. Full genome or exome sequencing will not be performed. Samples will be stored in a research biobank. For patients with incurable disease, quality of life and symptom burden will be monitored repeatedly using Danish questionnaires. Participants: The study will include: * Up to 100 patients with potentially curable disease * Up to 200 patients with incurable disease To participate, patients must: * Have confirmed bile duct cancer * Be eligible for curative, additional (adjuvant), or palliative treatment * Be over 18 years old * Provide written and verbal consent Patients cannot participate if they: * Had another cancer within the past 5 years (except early skin cancer or very early cervical cancer) * Cannot safely provide blood samples * Are unable to cooperate with study procedures Risks and Inconveniences: Participants will have extra blood samples taken, usually during regular hospital visits. Possible side effects include mild soreness or small bruises at the needle site. The extra blood amount (40 ml per sample) is considered medically insignificant. Participants will also spend time filling out questionnaires. The number and frequency of questions have been kept as low as possible while still providing meaningful data. Financial Information: Extra costs for blood sampling, laboratory analysis, and data collection will be covered by external research funding managed by Aarhus University Hospital. The researchers have no financial interest in the project. Patients will not receive financial compensation for participating. Recruitment and Consent: Potential participants are identified during routine clinical care. During a planned meeting with a doctor, patients receive written and verbal information about the study, including its purpose, risks, advantages, and disadvantages. The conversation takes place in a calm and private setting. Patients may bring a support person. They have time to ask questions and at least 24 hours to consider participation. Patients can withdraw their consent at any time without affecting their treatment. Consent must be given before any study-related procedures begin. Publication of Results: The results - whether positive or negative - will be presented at national and international conferences and submitted to peer-reviewed scientific journals. Ethical Considerations: All participants receive standard medical treatment. The risks and disadvantages are limited, and participants are unlikely to benefit directly from the study. However, the research may improve how biomarkers and patient-reported outcomes are used to predict prognosis and treatment response, potentially leading to better treatment for future patients with bile duct cancer.

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.