SIL204-SL Treatment for Locally Advanced Pancreatic Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Silexion Therapeutics Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-23

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: Safety, Efficacy

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.

Secondary objectives 4

1. To compare anti-tumor activity of SIL204-IR and SoC chemotherapy with SoC chemotherapy alone by objective response rate (ORR).
2. To compare anti-tumor activity of SIL204-IR and SoC chemotherapy with SoC chemotherapy alone by Disease Control Rate (DCR).
3. To evaluate the efficacy of SIL204-IR and SoC chemotherapy versus SoC chemotherapy alone in prolonging Progression Free Survival (PFS).
4. To explore the impact of SIL204-IR and SoC chemotherapy on participant reported symptoms, functional well-being as components of health-related quality of life (HRQoL).

Conditions and MedDRA coding

Non-Resectable Locally Advanced Pancreatic Cancer (LAPC)

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency, Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Capable of understanding and giving signed informed consent.
2. Male and female patients at least 18 years of age at the time of informed consent.
3. 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.
4. Patients have only one pancreatic tumor.
5. Confirmed KRAS mutation determined by tissue biopsy or liquid biopsy.
6. 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.
7. Patients must have clinically and/or radiographically documented (by Computed Tomography [CT] or MRI) measurable primary disease according to RECIST v1.1.
8. Eastern Cooperative Oncology Group (ECOG) Performance Scale status of ≤ 1.
9. 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
10. Patients who have undergone biliary stenting and with improving LFTs can be enrolled and treated as long as the LFTs are improving.
11. Patients who may become pregnant: a negative urine pregnancy test or serum pregnancy test (if required by local regulations) at Screening.
12. 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.

Exclusion criteria 22

1. 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.
2. For Segments 2 and 3: In addition to exclusion 1, patients with metastatic pancreatic cancer are excluded.
3. Any evidence of ascites (beyond trace).
4. Any prior therapy for the treatment of pancreatic malignancy.
5. Non-adenocarcinoma histology, pure squamous histology, acinar cell carcinoma, neuroendocrine tumor (NET) of the pancreatic cancer.
6. 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.
7. Major surgery, other than diagnostic surgery, within 4 weeks prior to trial entry without complete recovery.
8. 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.
9. Active, uncontrolled bacterial, viral, or fungal infections, requiring therapy.
10. 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.
11. 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.
12. Patients with Hepatitis C Virus (HCV) who have not completed curative antiviral treatment and HCV viral load above the limit of quantification.
13. Poorly controlled diabetes mellitus (DM) with episodes of hyper- or hypoglycemia requiring hospitalization within last 6 months.
14. History of clinically significant coagulopathy.
15. Pregnant or breast-feeding patients.
16. 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.
17. 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).
18. Not anticipated to receive therapy with any hypoxic cytotoxic agent (hypoxia-targeting drugs) in the SoC chemotherapy regimen.
19. Receiving active radiation to the tumor bed.
20. 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.
21. Unwillingness or inability to comply with the trial protocol for any reason.
22. Patients who cannot fulfil the requirements of the trial as judged by the Investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Primary trial endpoint: Overall survival (OS) is defined as the time from date of randomization to the date of death from any cause. OS will be assessed for up to 24 months following randomization. OS analysis will compare participants from Segments 2 & 3 who were randomized to receive the SIL204-SC dose selected for Segment 3 + SIL204-IT +SoC chemotherapy, with participants from Segments 2 & 3 who received SoC chemotherapy and who harbor KRAS G12D or KRAS G12V mutations.
2. Endpoints Segment 1: • AEs graded according to National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE v.6.0). • Dose limiting toxicity (DLT), which could prevent SIL204- SL from being administered at a higher dose.
3. Endpoints Segments 2 and 3: • Incidence, severity and causality of AEs graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; v.6.0). • OS, Progression free survival (PFS), complete response (CR), partial response (PR) or stable disease (SD), and Participant reported Outcomes (PROs).

Secondary endpoints 4

1. Difference between treatment arms in ORR, defined as proportion of participants achieving complete (CR) and partial response (PR) by CT using RECIST v1.1 criteria.
2. Difference between treatment arms in DCR, defined as proportion of participants achieving CR, PR and stable disease (SD) by CT using RECIST v1.1 criteria.
3. Comparison of PFS, defined as time from randomization to documented disease progression by CT using RECIST v1.1 criteria or death from any cause, whichever occurs first.
4. Difference between treatment arms in change from baseline in HRQoL scores as measured by the EORTC QLQ-C30 and its pancreatic cancer-specific module EORTC QLQ-PAN26, in participant reported pain assessed by visual analogue scale, and in generic health status as measured by the EQ-5D-5L.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Silexion Therapeutics Ltd.

Sponsor organisation

Silexion Therapeutics Ltd.

Address

12 Derekh Aba Hillel

City

Ramat Gan

Postcode

5250606

Country

Israel

Scientific contact point

Organisation

Silexion Therapeutics Ltd.

Contact name

Michal Yaron

Public contact point

Organisation

Silexion Therapeutics Ltd.

Contact name

Orit Pollack-Shragai

Third parties 5

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

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

Documents 11 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