Carbon Nanoparticle-Loaded Iron in the Treatment of Advanced Solid Tumor

Ib：Trial period: including screening period, treatment period and follow-up period. Screening period: -28\~-1 days, it is confirmed that the subjects meet the inclusion criteria and do not meet the exclusion criteria. Treatment period: Subjects who were successfully screened received CNSI-Fe intratumoral injection according to the protocol plan, administered once every two weeks, for a total of 4 doses. CNSI-Fe intratumoral injection selects 1\~3 suitable lesions to complete the corresponding dose of study drug injection (no more than 3 lesions). If the target lesion that has been injected intratumorally reaches CR or disappears and shrinks to the point where intratumoral injection is not possible, it is up to the investigator to judge whether the injection of the lesion can be stopped, and whether a new lesion can be selected for injection. After the completion of 4 doses, the investigator will judge according to the subject's situation, and if the benefit of the subject outweighs the risk, the number of doses can be appropriately increased. During the study period, safety checks were performed within 7 days before each dose and two weeks after the last dose. The tumor efficacy evaluation will be carried out within 3 days before the third dose, 3\~4 weeks after the fourth dose, and every 6 weeks thereafter (if disease progression is suspected, it can be checked in advance). Subjects who are evaluated for CR or PR for the first time need to be confirmed after 4\~5 weeks, and the tumor evaluation after the original plan of 6 weeks does not need to be carried out, and the next tumor evaluation will be carried out according to the original planned time. Samples were collected according to the established visit time points in the protocol flow chart. No other investigational products, drugs, or therapies for the purpose of treating tumors other than CNSI-Fe may be used. Supportive care measures used to control symptoms caused by the subject's malignancy are permitted. Subjects in the treatment period who terminate treatment early for any reason, or withdraw from the study before completing safety follow-up, are required to complete the end-of-treatment/end-of-study (EOT/EOS) visit as soon as possible within 7 days of early termination/early withdrawal from the study (results of the examination after the last treatment of the previous 7 days can be accepted). Follow-up period: Subjects who have received at least one CNSI-Fe treatment will enter a follow-up period after discontinuation of study drug treatment, which includes safety follow-up and efficacy follow-up. (1) Safety follow-up: A safety follow-up is required 28 days (±3 days) after the end of the last medication. (2) Disease progression as assessed by the investigator based on RECIST v1.1 and no new anti-tumor therapy has been initiated, subjects are required to be followed up for disease progression every 6 weeks at a frequency until disease progression as assessed by the investigator based on RECIST v1.1, initiation of new anti-tumor therapy, death, loss to follow-up, withdrawal of informed consent, or the end of this study, whichever occurs first. Criteria for the evaluation of local efficacy of CNSI-Fe: The revised RECIST v1.1 is based on RECIST v1.1 with appropriate modifications, and since CNSI-Fe is a local intratumoral injection, only the selection method of target lesions has been changed as a criterion for evaluating the efficacy of locally injected lesions. The changes in the revised RECIST v1.1 are as follows: 1. Lesions treated with local injection are defined as target lesions, and lesions not treated by local injection are defined as non-target lesions; 2. The tumor shrinkage effect at each evaluation time point was determined based on the evaluation of local injection treatment lesions; 3. The tumor shrinkage effect of the target lesion is the tumor shrinkage effect of the lesion treated by local injection. IIa：Phase IIa tentatively plans to develop three advanced solid tumor cohorts, each with about 10 subjects. After the completion of the Phase Ib multi-dose dose exploration phase, the specific design of the cohort expansion phase (such as cohort number, sample size, etc.) will be determined. Based on the existing data on safety, PK characteristics and preliminary efficacy, the sponsor and investigator will select the target tumor type for the Phase IIa cohort expansion study. Based on the clinical efficacy data obtained, the target tumor types to be explored in the Phase IIa study and the initiation of each arm may be adjusted. During the study, the sponsor and the investigator will analyze the study data in a timely manner and determine whether to stop a study cohort, increase the study cohort or change the dosing regimen based on the safety and efficacy data of the existing subjects.