Safety, Tolerability, and Preliminary Antitumor Activity of Non-Cationic Peptide-CD47 siRNA in Advanced Solid Tumors

A Clinical Trial of Non-cationic Peptide-CD47 siRNA for Safety, Tolerability, and Preliminary Antitumor Activity in Patients With Advanced Malignant Solid Tumors

This study evaluates a non-cationic peptide-CD47 siRNA nanocomplex for refractory advanced solid tumors. The candidate blocks the CD47-SIRPα "don't eat me" signal, repolarizes tumor-associated macrophages, and restores antitumor immunity. Using a 3+3 dose-escalation design (25, 50, 100 μg), the investigators aim to define the MTD and RP2D, providing a novel therapeutic approach and clinical evidence for siRNA drug development.

Study Overview

• Status: Not yet recruiting
• Conditions: Head and Neck Cancer; Solid Tumor Cancer; Metastases
• Intervention / Treatment: Biological: NCP-CD47 siRNA intratumorally injection

Detailed Description

This is a single-arm, open-label, non-randomized, single-center, prospective phase 1 clinical study conducted to evaluate the safety, tolerability, and preliminary antitumor activity of intratumorally injected NCP-CD47 siRNA in participants with advanced solid tumors. The primary objective is to assess the safety and tolerability of the NCP-CD47 siRNA formulation, and the secondary objective is to evaluate its preliminary antitumor activity. Safety refers to the frequency and severity of adverse events induced by NCP-CD47 siRNA, mainly assessed by the incidence of dose-limiting toxicities (DLTs), adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and routine laboratory examinations including hematological and biochemical indicators. Tolerability reflects participants' ability to tolerate adverse events related to the study drug, mainly assessed by the number of treatment discontinuations due to treatment-related adverse reactions, as well as changes in physiological and biochemical parameters, body weight, and adverse event reports (CTCAE 5.0). The primary endpoint is the incidence of DLTs and the number of treatment discontinuations due to treatment-related adverse reactions during the first treatment cycle of NCP-CD47 siRNA administration. The secondary endpoints include objective response rate (ORR), disease control rate (DCR), time to first complete response (CR) or partial response (PR), duration of response (DOR, defined as the interval from the first confirmed CR or PR to the first disease progression or death from any cause), duration of stable disease (SD, defined as the interval from the first confirmed SD to the first disease progression or death from any cause), progression-free survival (PFS, defined as the interval from the first administration of NCP-CD47 siRNA to the first disease progression or death from any cause), and overall survival (OS, defined as the interval from the first administration of NCP-CD47 siRNA to death from any cause). The study plans to enroll 3 to 18 participants with advanced solid tumors who have failed second-line chemotherapy, adopts a standard "3+3" dose-escalation design with three siRNA dose levels (25 μg, 50 μg, and 100 μg) and 3 participants enrolled in each dose cohort, administers the NCP-CD47 siRNA formulation via intratumoral injection, and ensures that the formulation is manufactured under GMP-compliant conditions, then aliquoted and reserved for clinical use in accordance with the clinical administration protocol.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female patients aged ≥18 years and ≤70 years.
• Histopathologically confirmed advanced recurrent/metastatic malignant solid tumors that are refractory to second-line treatment and have no available standard clinical therapeutic options (e.g., advanced soft tissue sarcoma, advanced head and neck squamous cell carcinoma, malignant melanoma, etc.).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
• Expected overall survival ≥3 months.
• Interval from the last chemotherapy, radiotherapy, or surgery ≥28 days.
• Interval from the last use of nitrosourea or mitomycin C ≥6 weeks.
• Adequate organ function, defined by the following laboratory parameters within 14 days prior to enrollment:
• Hemoglobin ≥90 g/L (no blood transfusion within 14 days).
• Absolute neutrophil count >1.5 × 10⁹/L.
• Platelet count ≥80 × 10⁹/L.
• Total bilirubin ≤1.5 × upper limit of normal (ULN).
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN in case of liver metastasis).
• Creatinine clearance ≥60 mL/min (calculated by Cockcroft-Gault formula).
• Left ventricular ejection fraction (LVEF) ≥50%.
• Signed written informed consent.

Exclusion Criteria:

• Participation in another investigational drug clinical trial within 4 weeks.
• Tumor located adjacent to major blood vessels or trachea.
• Uncontrolled cardiac clinical symptoms or diseases, including New York Heart -Association (NYHA) Class ≥2 heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant supraventricular/ventricular arrhythmias requiring treatment or intervention.
• Female patients who are pregnant or lactating.
• Active pulmonary tuberculosis, bacterial or fungal infection (≥Grade 2 per NCI-CTCAE version 5.0), active human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection.
• History of uncontrollable psychoactive substance abuse or presence of mental disorders.
• Any active autoimmune disease or history of autoimmune disease, including but not limited to uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism. Subjects with vitiligo or childhood asthma in complete remission (no adult intervention required) are eligible; subjects with asthma requiring bronchodilator therapy are excluded.
• Receiving immunosuppressive therapy.
• History of drug abuse or known medical, psychological, or social conditions that interfere with study compliance (e.g., alcoholism or illicit drug addiction).
• Known hypersensitivity, allergy, or intolerance to the study drug NCP-CD47 siRNA (including any excipients), or history of severe allergic reactions to any drugs, foods, or vaccines (e.g., anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, local Arthus reaction, etc.).
• Female subjects planning pregnancy, or male subjects whose partner plans pregnancy, from screening until 12 months after the last study drug injection.
• Any concomitant disease that, in the investigator's judgment, may seriously compromise patient safety or prevent the subject from completing the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intratumoral NCP-CD47 siRNA injection group	Biological: NCP-CD47 siRNA intratumorally injection; NCP-CD47 siRNA will be administered via intratumoral injection. A total of 5 doses will be given, with subsequent doses administered once weekly after the first injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)	DLT is defined as any Treatment-Related Adverse Event (TRAE) or clinically significant laboratory abnormality occurring during the DLT observation period. TRAEs include events judged by the investigator to be "definitely," "probably," or "possibly" related to the study treatment. Severity will be graded according to NCI-CTCAE v5.0.	From the first dose to the end of treatment at 9 weeks
Number of participants with treatment discontinuation due to treatment-related adverse events during the first treatment cycle	Treatment-related adverse events (TRAEs) will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Treatment discontinuation is defined as permanent cessation of NCP-CD47 siRNA administration due to investigator-determined TRAEs occurring during the first treatment cycle.	From the first dose to the end of treatment at 9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	Progression-Free Survival (PFS) is defined as the time interval from the start of treatment until the first documented occurrence of disease progression (PD) according to RECIST v1.1, or death due to any cause, whichever occurs first.	Up to 6 months from the date of the first dose.
Overall Survival	OS is defined as the time interval from the start of treatment to death due to any cause. For participants who are still alive at the end of the study, data will be censored at the last known date of follow-up.	Up to 12 months from the date of the first dose.
Objective Response	Number of participants achieving a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR) according to RECIST v1.1. Due to the small sample size, data will be reported as absolute counts.	Time Frame: Up to 6 months from the date of the first dose.

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Solid Tumor; siRNA; Overall survival; Cancer metastasis; Progress-free survival
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Head and Neck Neoplasms
• Other Study ID Numbers: 2026-892

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No