SIL204-SL Treatment for Locally Advanced Pancreatic Cancer

Trial details

Who runs it

Silexion Therapeutics Ltd.

Trial code

EU 2025-525157-39-00

Record updated

2026. június 23.

Original description

The overall aim of the trial is to evaluate the efficacy, and characterize safety and tolerability of SIL204-IR in combination with SoC chemotherapy in comparison with SoC chemotherapy in participants with non-resectable LAPC. The primary trial objective: To compare efficacy of the SIL204-IR and SoC chemotherapy in participants with LAPC harboring KRAS G12D or KRAS G12V by Overall Survival (OS) in comparison to SoC chemotherapy alone. Objective in Segment 1: To evaluate the safety and tolerability of three different SIL204-SC doses (low, medium, high) in combination with a standard SIL204-IT dose and SoC chemotherapy in participants with either metastatic pancreatic cancer or non-resectable LAPC. Further aims are to assess pharmacokinetics based on SIL204 plasma levels and to monitor cardiac function based on ECG. Objective in Segment 2: To compare the two selected SIL204-SC doses from Segment 1 (both on top of a standard dose of SIL204-IT plus SoC chemotherapy) against control (SoC chemotherapy), with the aim of selecting the best SIL204-SC dose for Segment 3.Read full original descriptionShow less

A Prospective, Randomized, Controlled, Multinational, Phase 2/3, Open-Label Trial to Evaluate the Efficacy and Safety of SIL204-SL Administered as an Integrated Therapeutic Regimen in Combination with Chemotherapy vs. Chemotherapy Treatment Alone in Participants with Locally Advanced Pancreatic Cancer

The overall aim of the trial is to evaluate the efficacy, and characterize safety and tolerability of SIL204-IR in combination with SoC chemotherapy in comparison with SoC chemotherapy in participants with non-resectable LAPC. The primary trial objective: To compare efficacy of the SIL204-IR and SoC chemotherapy in participants with LAPC harboring KRAS G12D or KRAS G12V by Overall Survival (OS) in comparison to SoC chemotherapy alone. Objective in Segment 1: To evaluate the safety and tolerability of three different SIL204-SC doses (low, medium, high) in combination with a standard SIL204-IT dose and SoC chemotherapy in participants with either metastatic pancreatic cancer or non-resectable LAPC. Further aims are to assess pharmacokinetics based on SIL204 plasma levels and to monitor cardiac function based on ECG. Objective in Segment 2: To compare the two selected SIL204-SC doses from Segment 1 (both on top of a standard dose of SIL204-IT plus SoC chemotherapy) against control (SoC chemotherapy), with the aim of selecting the best SIL204-SC dose for Segment 3.

Inclusion: Capable of understanding and giving signed informed consent; Patients who have undergone biliary stenting and with improving LFTs can be enrolled and treated as long as the LFTs are improving; Patients who may become pregnant: a negative urine pregnancy test or serum pregnancy test (if required by local regulations) at Screening; Patients who may become pregnant and men with partners who may become pregnant must agree to use one highly effective method of birth control plus one additional barrier method; Male and female patients at least 18 years of age at the time of informed consent; Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas, or mixed adenocarcinoma variants, including adenosquamous. Specific for Segment 1: a) In the first dosing group (low dose) patients with nonresectable LAPC stage 3 according to National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology criteria harboring any KRAS mutation can be enrolled. b) In medium and high dose group, patients with non-resectable LAPC stage 3 or metastatic pancreatic cancer harboring any KRAS mutation, having a maximum of 5 metastases confined to liver, lung, or peritoneum can be enrolled. Specific for Segments 2 and 3: Patients with non-resectable LAPC, stage 3 according to NCCN Clinical Practice Guidelines in Oncology criteria, harboring any KRAS mutation; Patients have only one pancreatic tumor; Confirmed KRAS mutation determined by tissue biopsy or liquid biopsy; Pancreatic tumor is accessible for IT administration by EUS in at least 3 designated tumor sites as determined by the radiologist/gastroenterologist performing the EUS IT insertion, according to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines; Patients must have clinically and/or radiographically documented (by Computed Tomography [CT] or MRI) measurable primary disease according to RECIST v1.1; Eastern Cooperative Oncology Group (ECOG) Performance Scale status of ≤ 1; Demonstrate adequate organ function as defined by: - Estimated Glomerular Filtration Rate (eGFR) ≥ 45 mL/min (by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) - Absolute neutrophil count (ANC) ≥ 1.5 billion/L - Platelets ≥ 100 × billion/L - Hemoglobin ≥ 8.5 mg/dL - Liver function tests (LFTs) • Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 times upper limit of normal (ULN) • Bilirubin ≤ 1.5 × ULN - Serum albumin ≥ 3 g/dL Specifically for Segment 1: - Lactate Dehydrogenase (LDH) ≤ 1.5 ULN.

Exclusion: Chronic carriers of Hepatitis B Virus (HBV) infection who are not on HBV therapy or resolved prior HBV infection who are HBsAg-positive, or according to the Investigator’s clinical judgment are at risk for HBV re-activation; Concomitant disease or condition that could interfere with the conduct of the trial, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this trial; Not anticipated to receive therapy with any hypoxic cytotoxic agent (hypoxia-targeting drugs) in the SoC chemotherapy regimen; Receiving active radiation to the tumor bed; Patients who are currently participating or have participated in another investigational product trial in which the investigational product was administered within 5 half-lives of that product prior to signing the ICF; Any prior therapy for the treatment of pancreatic malignancy; Major surgery, other than diagnostic surgery, within 4 weeks prior to trial entry without complete recovery; New York Heart Association (NYHA) Class 3 or 4, cardiac disease, myocardial infarction within 6 months prior to chemotherapy Cycle 1, Day 1, unstable arrhythmia or symptomatic peripheral arterial vascular disease; For all segments: Patients with resectable pancreatic cancer (PC), borderline resectable pancreatic cancer (BRPC) or cancers other than PC. Cross-sectional imaging of abdomen with CT or MRI and chest X-ray of lung must be used in this assessment. There will be a central review for this criterion by a radiologist; Patients with Human Immunodeficiency Virus (HIV) with detectable viral load (Polymerase Chain Reaction [PCR] test result) and/or who had an opportunistic infection within the past 12 months; Patients with Hepatitis C Virus (HCV) who have not completed curative antiviral treatment and HCV viral load above the limit of quantification; Poorly controlled diabetes mellitus (DM) with episodes of hyper- or hypoglycemia requiring hospitalization within last 6 months; History of clinically significant coagulopathy; For Segments 2 and 3: In addition to exclusion 1, patients with metastatic pancreatic cancer are excluded; Non-adenocarcinoma histology, pure squamous histology, acinar cell carcinoma, neuroendocrine tumor (NET) of the pancreatic cancer; Active, uncontrolled bacterial, viral, or fungal infections, requiring therapy; Active pancreatitis confirmed by: • Serum amylase or lipase ≥ 3 × ULN, or • Abdominal pain consistent with pancreatitis (epigastric pain radiating to the back), or • Characteristic evidence of pancreatitis on imaging (CT, MRI, or ultrasound); History of malignancy, unless the participant has been disease-free for ≥3 years and is not currently receiving chemotherapy, poly (ADP-ribose) polymerase (PARP) inhibitor therapy, or immunotherapy for cancer treatment. Exceptions: Adequately treated non-melanoma skin cancer, carcinoma in situ, and use of hormonal therapy for breast or prostate cancer are permitted; Pregnant or breast-feeding patients; Unwillingness or inability to comply with the trial protocol for any reason; Patients who cannot fulfil the requirements of the trial as judged by the Investigator; Any evidence of ascites (beyond trace).

EU CTIS 2025-525157-39-00