Clinical trials

Study Primary Objective: To evaluate the efficacy of CNSI-Fe intra-tumoral injection combined with radiotherapy in patients with solid tumors. Study Secondary Objectives: 1. To evaluate the efficacy of CNSI-Fe intra-tumoral injection combined with radiotherapy at both injected and non-injected lesions; 2. To evaluate the safety and tolerability of CNSI-Fe intra-tumoral injection combined with radiotherapy in patients with solid tumors; 3. To evaluate the pharmacokinetic (PK) characteristics of CNSI-Fe intra-tumoral injection combined with radiotherapy in patients with solid tumors. Study Population: Patients with histologically or cytologically confirmed solid tumors including soft tissue sarcoma, head and neck squamous cell carcinoma, etc., who are assessed by the investigator as suitable for standard radiotherapy including preoperative neoadjuvant radiotherapy (Cohort A1) or definitive radiotherapy for patients not suitable for surgery (Cohort A2) Study Drug Administration Schedule: Single administration, 2 weeks per administration cycle, total 1-4 cycles Study Primary Endpoint: Objective Response Rate (ORR) assessed according to RECIST 1.1 criteria Study Key Secondary Endpoints: 1. Patients with unresectable locally advanced or advanced solid tumors: Local Control Rate (LCR), Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DOR), Time to Progression (TTP), Time to Response (TTR), and Overall Survival (OS); 2. Patients receiving preoperative neoadjuvant therapy: Major Pathological Response (MPR), Disease-Free Survival (DFS), Disease Control Rate (DCR);

Independently developed by Sichuan Yingrui Pharmaceutical Technology Co., Ltd., CNSI-Fe is an innovative anti-cancer drug with Fe2+ as the active ingredient, which exerts anti-tumor effects by regulating the ferroptosis pathway. CNSI-Fe intratumoral injection has the following three effects: 1. Nanocarbon can increase the content of hydrogen peroxide in tumor cells and tumor microenvironment, and is a reactive oxygen species that catalyzes hydrogen peroxide through the Fenton reaction of iron ions to produce "ferroptosis", which complements each other; 2. The adsorption of Fe2+ by nanocarbon can help Fe2+ better enter the cell, thereby exerting anti-tumor effects; 3. The lesion localization and lymphatic tracing functions of nanocarbon are retained. The combination of the regulatory mechanism of ferroptosis and the characteristics of nanocarbon particles has increased the advantages of new nanopharmaceuticals in cancer prevention and treatment. At present, CNSI-Fe has carried out a first-in-human phase I clinical trial of dose escalation in subjects with advanced solid tumors in China, and has conducted safety and efficacy exploration in four dose groups, including: 30 mg, 60 mg, 90 mg, and 120 mg, and the overall safety and tolerability of the 16 subjects enrolled have been good, no obvious liver and kidney impairment and hematologic toxicity have been observed, and only one subject in the 90 mg dose group has a dose-limiting toxicity (DLT) event; Partial response (PR) was observed in 1 subject (30 mg group), complete tumor response (CR) was observed in 1 subject (60 mg group), and stable tumor (SD) was observed in 11 subjects (including 1 in the 30 mg group, 2 in the 60 mg group, 5 in the 90 mg group, and 3 in the 120 mg group), and the disease control rate (DCR) of the trial treatment was 87%. This Phase I clinical study is planned to continue dose exploration at 150 mg or higher. Therefore, based on the results of the Phase I clinical trial obtained, it is planned to conduct this Phase Ib/IIa clinical study in subjects with advanced solid tumors in China to further evaluate the safety, tolerability, pharmacokinetic (PK) characteristics and preliminary efficacy of CNSI-Fe intratumoral injection and multiple administration, so as to provide a basis for clinical development in the later stage.