Conditions: Advanced Solid Tumor Lung Cancer Pancreas Cancer Breast Cancer Thyroid Cancer Colorectal Cancer Cervical Cancer Ovarian Cancer Vulva Cancer
Keywords: Intratumoral Injection Carbon Nanoparticle-Loaded Iron Advanced Solid Tumor Ferroptosis Dose Limited Toxicity Maximum Tolerated Dose Pharmacokinetics
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 19
Healthy volunteers: no

Brief summary:
This Phase I clinical trial aims to evaluate the safety, tolerability, pharmacokinetics (PK) profile and preliminary efficacy of intratumoral injection of Carbon Nanoparticle-Loaded Iron \[CNSI-Fe(II)\] in patients with advanced solid tumors. The study also aims to observe dose-limiting toxicities (DLT) of CNSI-Fe(II) to determine the maximum tolerated dose (MTD) or the highest injectable dose in humans, providing dosing guidelines for future clinical studies. CNSI-Fe(II) shows promise as an innovative tumor therapeutic agent due to its unique properties of ferroptosis. The study primarily focuses on assessing the potential efficacy of CNSI-Fe(II) in patients with advanced solid tumors, particularly in patients with Kras mutation, e.g., pancreatic cancer patients.

Detailed description:
Indications: This study targets patients with advanced solid tumors who have either failed standard treatments (progression or intolerance) or lack available standard treatment options. Common tumor types include colorectal, pancreatic, breast, gastric, cervical, lung, head and neck, and prostate cancers.

Objectives: The primary goal is to assess the safety and tolerability of intratumoral injections of Carbon Nanoparticle Loaded Iron \[CNSI-Fe(II)\] in advanced solid tumor patients. This involves identifying dose-limiting toxicities (DLT) and determining the maximum tolerated dose (MTD) or highest injectable dose for subsequent clinical dosing decisions. Secondary objectives include evaluating the pharmacokinetics (PK) of CNSI-Fe(II) and its preliminary efficacy. Exploratory objectives is to understand the pharmacodynamics (PD) of CNSI-Fe(II), exploring the relationship between tumor size, injection dose, and drug concentration.

Participants: Up to 30 subjects will participate across 3 to 6 centers, with the final number dependent on dose group evaluations and tolerability.

Exit Criteria: Subjects may be withdrawn by researchers if they deviate from the protocol, impacting safety or efficacy assessment. Subjects can also voluntarily withdraw per guidelines, and their reasons will be documented. Efforts will be made to complete assessments for withdrawn cases.

Dose Selection: Based on animal toxicology and effective dose data, a starting dose of 0.5 mg/kg (escalating to 30 mg, 60 mg and 90 mg) is selected. Adjustments may occur if DLT is observed or MTD is not reached.

As of March 28, 2024, only one case of DLT occurred in the 90 mg dose group among the 30 mg, 60 mg, and 90 mg dose groups, demonstrating favorable safety and tolerability. The study has successfully passed the SRC meeting, allowing for further dose exploration at 120 mg, 150 mg, and potentially higher doses. Therefore, this protocol is hereby revised.

Study Design: This open-label Phase I trial assesses CNSI-Fe(II) intratumoral injections in advanced solid tumor patients. The study includes screening, treatment (with DLT evaluation), and follow-up phases.

Dose Escalation: The "3+3 method" guides dose escalation. Enrollment occurs in dose groups; dose escalation decisions are based on DLT occurrence.

DLT Evaluation: DLTs are defined using toxicity criteria, assessed during the first cycle (21 days). Escalation decisions depend on DLT occurrence.

DLT is defined as toxicities that are considered definitely or possibly related to the investigational drug CNSI-Fe(II) and occur within the first cycle (21 days) after the first dose. This includes Grade 4 hematological toxicity, Grade 3 hematological toxicity lasting \>7 days after optimal treatment, Grade 3 thrombocytopenia with bleeding or requiring platelet transfusion, and Grade 3 neutropenia with fever.

Non-hematological toxicity:

1. Grade 3 cardiac toxicity lasting more than 3 days after optimal treatment or Grade 4 cardiac toxicity.
2. Grade 3 liver toxicity (for subjects with liver or bone metastasis and baseline liver enzyme ALT, AST, or ALP at Grade 2, ALT, AST, or ALP \>10×ULN) lasting more than 3 days after optimal treatment or Grade 4 liver toxicity.
3. Any Grade 3 non-hematological toxicity (excluding laboratory abnormalities) lasting more than 7 days after optimal treatment, except for Grade 3 nausea, Grade 3 vomiting, or Grade 3 diarrhea.
4. Any Grade 4 non-hematological toxicity (excluding laboratory abnormalities).
5. Any Grade 3 or 4 non-hematological laboratory abnormality if it requires medical intervention, leads to hospitalization, or persists at Grade 3 or above for 7 days or more after discontinuation of the drug.

Other:

1. Any Grade 5 toxicity.
2. Other toxicities requiring early termination of CNSI-Fe(II) treatment as decided by the investigator and sponsor.

Besides evaluating the safety and tolerability of CNSI-Fe(II), this study will also preliminarily assess the efficacy of CNSI-Fe(II) in patients with advanced solid tumors. The investigator will evaluate CNSI-Fe(II)'s efficacy based on imaging examinations (computed tomography \[CT\], positron emission tomography \[PET\]/CT, or magnetic resonance imaging \[MRI\]), following the revised RECIST v1.1 criteria. Baseline imaging evaluations will be conducted within 28 days before the first treatment in the study. Subsequent tumor assessments will be performed for all subjects in the study at weeks 3-4 and, for those entering the maintenance phase, at weeks 7-8. Confirmation will be required for subjects achieving a complete response (CR) or partial response (PR) at least 4 weeks after the initial response. Baseline evaluations must include chest, abdomen, pelvis, skull (to exclude brain metastases), and other suspected tumor sites. Subsequent evaluations should reassess all measurable and evaluable lesions identified at baseline, including chest, abdomen, pelvis, and other suspected tumor sites. The imaging methods used for efficacy evaluation during the study must be consistent with the baseline imaging evaluation.

Medicinal Products: The study uses CNSI-Fe(II) consisting of a nanoparticle carbon dispersion injection and injectable ferrous sulfate.

Preparation of CNSI-Fe(II): Take one vial of injectable ferrous sulfate, keeping the aluminum cap and rubber stopper tightly closed and removing only the plastic outer cap of the aluminum-plastic combination cap. Slowly draw an appropriate amount of nanoparticle carbon dispersion injection using a suitable syringe and inject it into the vial containing ferrous sulfate, ensuring the solution is thoroughly mixed. The preparation of CNSI-Fe(II) should be done under aseptic conditions, avoiding exposure to air. It should be prepared and used at room temperature within 6 hours.

Dosing: Dosing varies per phase and dose group, ensuring administration within the target tumor.

PK and PD Analysis: Concentration-time curves, AUC, Cmax, Tmax, and PD marker levels are assessed using descriptive statistics.

Statistical Analysis: Descriptive statistics are employed for demographic, safety, efficacy, and PK/PD data. No formal hypothesis testing is planned.

Study Duration: The study will continue from the approval of the study by the Ethics Committee (EC) until the expected sample size is reached, subject to actual circumstances. The study is anticipated to end 28 days after the last subject has received a maximum of two doses of the study drug. After the study is completed, subjects who continue to achieve Complete Response (CR) or Partial Response (PR) and are determined by the investigator to still benefit from the treatment can continue to receive the study drug as a gift until disease progression, intolerable toxicity, or the investigator determines it is not appropriate to continue the study drug or the sponsor terminates the study.

Arms:
arm 1: 30 mg

CNSI-Fe(II) 30 mg: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion. arm 2: 60 mg

CNSI-Fe(II) 60 mg: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an dditional dose may be administered based aon the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion. arm 3: 90 mg

CNSI-Fe(II) 90 mg: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion. arm 4: 120 mg

CNSI-Fe(II) 120 mg: The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution. arm 5: 150 mg

CNSI-Fe(II) 150 mg: The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution.

Interventions: intervention 1: CNSI-Fe(II) 30 mg intervention 2: CNSI-Fe(II) 60 mg intervention 3: CNSI-Fe(II) 90 mg intervention 4: CNSI-Fe(II) 120 mg intervention 5: CNSI-Fe(II) 150 mg
Intervention descriptions: intervention 1: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion. intervention 2: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion. intervention 3: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion. intervention 4: The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution. intervention 5: The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution.

Protocol document:
Prot_SAP_000.pdf: 
A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic 
(PK) Characteristics, and Preliminary Efficacy of Intratumoral Injection of 
Ferrous Ion Adsorbed Carbon Nanoparticle Suspension Injection (CNSI-Fe) in 
Patients with Advanced Solid Tumors 
 
Study Protocol 
NCT06048367 
 
Version/Date: V3.1/March 28, 2024 
 
 
Protocol Number: YR-2021-01-CNSI-Fe 
 
Screening Number: 
 
Investigator: Yongsheng Wang 
 
Clinical Trial Institution: West China Hospital, Sichuan University 
 
Trial Site Address: No. 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province 
 
Sponsor: Sichuan Enray Pharmaceutical Technology Company 


Study Protocol 
Indication: Patients with advanced solid tumors, such as colorectal cancer, pancreatic 
cancer, breast cancer, gastric cancer, cervical cancer, lung cancer, head and neck 
cancer, cholangiocarcinoma, renal cancer, prostate cancer, vulvar cancer, etc., who 
have failed standard treatment (disease progression after treatment or unable to 
tolerate treatment) or have no standard treatment available. 
 
Study Objectives 
Primary Objectives: To evaluate the safety and tolerability of intratumoral injection 
of different doses of the ferrous iron adsorbed carbon nanoparticle suspension 
injection (CNSI-Fe) in patients with advanced solid tumors, and to observe the 
dose-limiting toxicity (DLT) of CNSI-Fe, and to determine the maximum tolerated 
dose (MTD) or the maximum injectable dose in humans, which will provide a basis 
for the selection of doses in subsequent clinical studies. 
 
Secondary Objectives: To evaluate the pharmacokinetic (PK) characteristics of 
intratumoral injection of different doses of CNSI-Fe in patients with advanced solid 
tumors; 
To preliminarily evaluate the efficacy of intratumoral injection of different doses of 
CNSI-Fe in patients with advanced solid tumors. 
 
Exploratory Objectives: To evaluate the intratumoral pharmacodynamic (PD) 


characteristics of intratumoral injection of different doses of CNSI-Fe in patients with 
advanced solid tumors (not mandatory); 
To evaluate the intratumoral PK characteristics of intratumoral injection of different 
doses of CNSI-Fe in patients with advanced solid tumors (not mandatory); 
To explore the relationship between tumor size and CNSI-Fe injection dose, as well as 
the dose-effect relationship of CNSI-Fe concentration, in patients with advanced solid 
tumors receiving intratumoral injection of CNSI-Fe (not mandatory). 
 
Study Endpoints 
Primary Endpoints: 
Safety 
Adverse events (AEs), vital signs, physical examinations, laboratory tests, Eastern 
Cooperative Oncology Group (ECOG) performance status (see Appendix 1), 12-lead 
electrocardiogram (ECG), echocardiography, etc. during the study period; 
Incidence of dose-limiting toxicities (DLTs). 
 
Secondary Endpoints: 
Pharmacokinetics (PK) 
Including but not limited to area under the curve (AUC0-t), peak concentration (Cmax), 
AUC0-∞, time to peak concentration (Tmax), apparent volume of distribution (Vd), 
elimination rate constant (Ke), half-life (t1/2), apparent clearance (CL), mean residence 
time (MRT), Vd/bioavailability (F), CL/F, accumulation ratio, etc. 


 
Efficacy 
Evaluation of anti-tumor efficacy of the injected lesions based on the revised 
Response Evaluation Criteria in Solid Tumors version 1.1 (revised RECIST v1.1) (see 
Appendix 2), including objective response rate (ORR) and disease control rate (DCR); 
Evaluation of overall anti-tumor efficacy based on the Response Evaluation Criteria 
in Solid Tumors version 1.1 (RECIST v1.1) (see Appendix 3). 
Note: The primary efficacy endpoints are ORR and DCR of the injected lesions based 
on the revised RECIST v1.1. 
 
Exploratory Endpoints 
Exploration of the levels of hydrogen peroxide (H2O2), peroxidase (POD), 
malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPX4), 
hydroxyl radical (·OH), etc. in tumor tissue samples after administration (optional); 
Exploration of the intratumoral PK study in the injected lesions, if available (not 
mandatory); 
Exploration of the dose-response relationship between tumor size and administered 
dose/concentration using three-dimensional reconstruction technology (3D-CTA) to 
guide rational dosing in future clinical trials (not mandatory). 
 
Total number of subjects: up to 30 cases, the final sample size will depend on the 
number of dose groups evaluated and the tolerability in each dose group.  


Number of study centers: expected to be 3-6 centers. 
 
Subject Selection Criteria 
Inclusion Criteria： 
Patients must meet all of the following criteria to be eligible for enrollment: 
Understand and voluntarily sign the written informed consent form (ICF), have the 
willingness and ability to comply with all trial requirements; 
Signed the ICF and are male or female aged 18-80 years (inclusive) at the time of 
signing the ICF; 
Patients with histologically or cytologically confirmed advanced solid tumors, for 
whom standard treatment is ineffective (disease progression after treatment or unable 
to tolerate treatment) or there is no effective standard treatment available, such as 
colorectal cancer, pancreatic cancer, breast cancer, gastric cancer, cervical cancer, 
lung cancer, head and neck cancer, cholangiocarcinoma, renal cell carcinoma, prostate 
cancer, vulvar cancer, etc. 
Note: Patients with advanced solid tumors who are unable to receive standard 
treatment due to any reason leading to disease progression, or patients with tumor 
types insensitive to current standard treatments (such as pancreatic cancer, 
undifferentiated thyroid cancer, and sarcoma) who have disease progression after 
receiving the first course of standard treatment, can be included. 
According to RECIST v1.1, have at least one measurable lesion, and this lesion has 
not received prior radiation therapy (unless there is clear progression of the lesion 


after radiation therapy), nor has it undergone a tissue biopsy within 7 days prior to the 
first dose; 
Have an injectable lesion (e.g. can be directly injected or assisted by medical imaging 
instruments); 
ECOG performance status of 0-1 within 7 days prior to the first dose; 
Expected survival time ≥12 weeks; 
Drug-related adverse reactions (ADRs) from prior treatments have recovered to 
≤Grade 1 per NCI CTCAE v5.0 (except for alopecia) prior to screening; 
Left ventricular ejection fraction (LVEF) ≥50%; 
Within 7 days prior to the first dose, have adequate hematologic and end-organ 
function, with laboratory tests meeting the following criteria: 
a) Hematology 
No use of granulocyte colony-stimulating factor (G-CSF) within 14 days prior to 
hematology laboratory tests, and absolute neutrophil count (ANC) ≥1.5×109/L; 
No platelet transfusion within 14 days prior to hematology laboratory tests, and 
platelet count (PLT) ≥90×109/L; 
No blood transfusion or use of erythropoietin within 14 days prior to hematology 
laboratory tests, and hemoglobin (Hb) ≥90 g/L; 
b) Renal function 
Serum creatinine (Cr) ≤1.5×upper limit of normal (ULN) or calculated creatinine 
clearance (Ccr) ≥50 mL/min using the Cockcroft-Gault formula (only calculated if 
baseline Cr >1.5×ULN); 


c) Hepatic function 
Total bilirubin (TBIL) ≤1.5×ULN (≤3.0×ULN for patients with Gilbert's syndrome or 
liver metastases); 
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline 
phosphatase (ALP) ≤3×ULN, patients with confirmed liver or bone metastases must 
meet the following criteria: 
Patients with confirmed liver metastases: AST and ALT ≤5×ULN; 
Patients with confirmed bone metastases: ALP ≤5×ULN; 
Serum albumin ≥2.8 g/dL; 
d) Coagulation function 
International normalized ratio (INR) or prothrombin time (PT) and activated partial 
thromboplastin time (aPTT) ≤1.5×ULN; 
Note: For patients with injectable lesions in the skin and/or subcutaneous tissue who 
are receiving anticoagulant therapy, prolonged INR, PT and aPTT are allowed, as 
bleeding can be controlled by direct pressure application, as determined by the 
investigator. 
For female patients of childbearing potential (WOCBP), a negative pregnancy test 
result must be obtained within 7 days prior to the first dose of the study drug, and they 
must agree to use highly effective contraception or abstinence during the study drug 
treatment and for 6 months after the end of study drug treatment. In addition, female 
patients must be non-lactating and agree not to donate eggs during this period; 
Note: WOCBP is defined as a female who has experienced menarche but has not 


undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not 
post-menopausal. Post-menopausal is defined as a female over the age of 45 years 
who has not had menses for 12 consecutive months in the absence of other biological 
or physiological causes. Additionally, females 55 years of age or younger must have a 
serum follicle-stimulating hormone (FSH) level >40 mIU/mL to be considered 
post-menopausal. 
Hormone replacement therapy (HRT) may artificially suppress a woman's FSH levels 
and may require a washout period before the physiological FSH level can be restored. 
The duration of the washout period depends on the type of HRT. The following 
washout period durations are suggested as guidance, and the investigator should use 
their judgment based on the FSH level test results: 
At least 1 week for vaginal hormonal products (rings, creams, gels); 
At least 4 weeks for transdermal products; 
At least 8 weeks for oral products; 
Up to 6 months for other non-oral, non-transdermal products. 
If during the washout period the serum FSH level is >40 mIU/mL, the patient may be 
considered post-menopausal. 
Male patients must agree to use highly effective contraception or abstinence during 
the study drug treatment and for 6 months after the end of study drug treatment. In 
addition, male patients must agree not to donate sperm during this period. 
 
Exclusion Criteria: 


Patients who meet any of the following criteria will not be eligible to participate in 
this clinical study: 
History or current presence of iron metabolism disorders (except for iron deficiency 
anemia), such as thalassemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency 
(favism), etc.; 
History or current evidence of hollow organ perforation at the injection site; 
History or current skin breakdown, redness, swelling, necrosis, or bleeding at the 
injection site that may affect the administration of the investigational drug; 
Received radiotherapy or any anti-cancer therapy within 4 weeks prior to the first 
administration of the investigational drug, or the time since the last anti-cancer 
treatment [including but not limited to chemotherapy, targeted therapy, 
immunotherapy, National Medical Products Administration (NMPA)-approved 
anti-cancer Chinese patent medicines, and Chinese medicines with anti-tumor effects] 
is less than 5 half-lives, whichever is shorter; 
Underwent major surgery, significant trauma, or have persistent unhealed wounds and 
ulcers within 4 weeks prior to the first administration of the investigational drug; 
Presence of life-threatening clinical manifestations of brain and central nervous 
system metastases at the time of enrollment; 
Uncontrolled hypertension (systolic blood pressure ≥150 mmHg or diastolic blood 
pressure ≥100 mmHg); 
Uncontrolled cancer-related pain; 
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated 


drainage (once/month or more frequently); 
Concurrent malignancy within 5 years prior to the first administration of the study 
treatment, except for curatively treated non-melanoma skin cancer, localized prostate 
cancer, ductal carcinoma in situ or stage I uterine cancer, cervical carcinoma in situ, or 
breast carcinoma in situ; 
Received live virus vaccines within 4 weeks prior to the first administration of the 
investigational drug; 
Note: Seasonal influenza vaccines are usually inactivated influenza vaccines and are 
allowed; however, intranasal influenza vaccines (e.g., FluMist®) are attenuated live 
vaccines and are not allowed. 
History of immunodeficiency, including positive for human immunodeficiency virus 
(HIV) or other acquired or congenital immunodeficiency diseases, or history of organ 
transplantation; 
Active hepatitis B virus (HBV) infection [positive for hepatitis B surface antigen 
(HBsAg) or hepatitis B core antibody (HBcAb) and HBV DNA >500 IU/mL], 
hepatitis C virus (HCV) infection [positive for HCV antibody and HCV RNA by 
polymerase chain reaction (PCR) above the upper limit of normal], or positive for 
anti-human immunodeficiency virus antibody (Anti-HIV); 
Serious chronic or active infections (including tuberculosis infection) requiring 
systemic antibacterial, antifungal, or antiviral treatment within 4 weeks prior to the 
start of the study treatment; 
Note: Patients with viral hepatitis are allowed to receive antiviral treatment. 


Severe cardiovascular diseases, including but not limited to: 
History of acute coronary syndrome or coronary artery angioplasty/stent 
placement/bypass surgery within the past 6 months; 
New York Heart Association (NYHA) (see Appendix 4) class II-IV congestive heart 
failure (CHF), or history of NYHA class III or IV CHF. 
Active psychiatric disorders (schizophrenia, severe depressive disorder, bipolar 
disorder, etc.); 
Known allergy or intolerance to the active ingredient, excipients, or other iron 
supplementation products of the investigational drug; 
Participated in other interventional clinical studies within 4 weeks prior to the start of 
the study treatment (calculated from the first day after the last dose of the previous 
study, except for those who did not use any investigational drugs or medical devices); 
Any other condition that the investigator deems unsuitable for the patient to 
participate in this study. 
 
Criteria for Suspension of Clinical Trials:  
The trial will be suspended until the cause is confirmed and the safety review 
committee (SRC) composed of the sponsor and investigators, etc. discusses and 
determines that the trial can be restarted, under the following circumstances: 
Any death of a subject not due to disease progression within 21 days (inclusive) after 
injection of CNSI-Fe; 
Multiple subjects discontinue study drug treatment for reasons other than disease 


progression; 
The incidence and severity of adverse drug reactions indicate that the risks of the 
study drug regimen outweigh the benefits; 
The quality of data recording is too poor, inaccurate and/or incomplete. 
 
Withdrawal Criteria: 
Withdrawal Decided by Investigators: Withdrawal decided by investigators refers 
to the situation where a selected participant is deemed unsuitable to continue the study 
during the research process, and the investigator decides to withdraw the participant 
from the study. This includes, but is not limited to, the following situations: 
The participant has seriously deviated from or violated the protocol, and this has 
affected the evaluation of the drug's efficacy or safety, so the participant must be 
withdrawn from the study; 
The investigator believes that the participant should be withdrawn from the study for 
other reasons. 
Withdrawal Decided by Participants: According to the Good Clinical Practice 
(GCP) for Pharmaceutical Trials and the International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline E6, all 
participants have the right to withdraw from the study at any time during the trial, or 
if the participant no longer accepts medication and testing but does not explicitly 
request withdrawal, this is also considered "withdrawal" (or "dropout"). The reasons 
for withdrawal should be understood as much as possible and recorded, such as: 


unable to tolerate certain adverse events; unable to continue the clinical study due to 
other reasons; or lost to follow-up without explanation, etc. 
Handling of Withdrawn Cases 
Investigators must record the reason for participant withdrawal in the electronic case 
report form (eCRF), and try to contact the participant as much as possible to complete 
the assessments that can be done. Regardless of the reason, the eCRF of the 
withdrawn case should be retained. For withdrawn cases where adverse events exist at 
the time of study termination, the follow-up requirements for the adverse events are 
described in Section 8.6. 
 
The basis for dose selection: According to the "Guidance Principles for Estimating 
the Maximum Recommended Starting Dose for First-in-Human Clinical Trials of 
Healthy Adult Volunteers" issued by the NMPA, and with reference to the Maximum 
Recommended Starting Dose (MRSD) for anticancer drugs in ICH S9 "Nonclinical 
Evaluation for Anticancer Pharmaceuticals", the design of the dosage regimen 
depends on the data from the long-term toxicity studies of CNSI-Fe in animals. In the 
toxicity study with 2 intramuscular injections on Day 1 and Day 4, followed by a 
4-week recovery period in rats, the Highest Non-Severely Toxic Dose (HNSTD) was 
20 mg/kg (calculated as Fe2+), corresponding to a Human Equivalent Dose (HED) of 
3.6 mg/kg; in the toxicity study with Beagle dogs, the HNSTD was 15 mg/kg, 
corresponding to an HED of 8.7 mg/kg. Assuming an adult body weight of 60 kg and 
a safety factor of 6, the MRSD for humans is estimated to be approximately 0.6 


mg/kg and 1.45 mg/kg, respectively. 
 
Considering the effective doses in preclinical studies, in multiple solid tumor 
xenograft models (human colon cancer COLO 205, human breast cancer 
MDA-MB-231, human breast cancer HCC1954, and human colon cancer HT-29 cells), 
CNSI-Fe (calculated as Fe2+, 0.1875 mg, 0.375 mg, 0.50 mg, 0.75 mg, administered 
twice on Day 1 and Day 4) significantly inhibited tumor growth. The effective dose 
and the maximum effective dose were 0.1875 mg and 0.75 mg, respectively. 
Assuming a mouse body weight of 20 g and an adult human body weight of 60 kg, the 
corresponding human equivalent doses are 0.84 mg/kg and 3.36 mg/kg, respectively. 
 
Considering the above factors and the safety of the first-in-human trial, this study 
selected 0.5 mg/kg as the starting dose, with escalating doses of 0.5 mg/kg, 1.0 mg/kg, 
and 1.5 mg/kg. Calculated based on an average human body weight of 60 kg, the 
escalating doses are 30 mg, 60 mg, and 90 mg (calculated as Fe2+). If ≥2 subjects 
experience DLT at the 90 mg dose, the dose will be reduced to 75 mg for safety and 
tolerability observation; if the dose escalation to 90 mg does not reach the MTD, the 
SRC will discuss whether to further escalate the dose to 120 mg, 150 mg, or even 
higher, based on the available safety, PK/PD, and preliminary efficacy data (if 120 mg 
still does not reach the MTD, the SRC will discuss whether to stop the dose escalation 
or directly proceed to 150 mg or even higher doses). 
 


 
Study Design: This is an open-label, dose-escalation Phase I clinical study conducted 
in patients with advanced solid tumors, aiming to evaluate the safety, tolerability, 
PK/PD characteristics, and preliminary efficacy of CNSI-Fe intratumoral injection in 
patients with advanced solid tumors. 
 
Study Period: The study includes a screening period, a treatment period (including 
DLT evaluation period), and a follow-up period. 
 
Screening Period: -28 to -1 days, to confirm that the subjects meet the inclusion 
criteria and do not meet the exclusion criteria. 
Treatment Period (including DLT Evaluation Period): The DLT evaluation period 
is the first treatment cycle (duration: 21 days). During the DLT evaluation period, all 
subjects will receive CNSI-Fe intratumoral injection according to the protocol plan 
(preferentially selecting 1 suitable lesion for injection, tentatively with 1 injection on 
Day 1; if the corresponding dose of the investigational drug cannot be completed in 1 
lesion, other lesions can be injected simultaneously; the dosing regimen may be 
adjusted by the sponsor and investigator based on the PK characteristics of this study). 
Safety assessments will be performed on Day 7, Day 14, and Day 21 after the first 
dose to evaluate DLT. 
After the DLT evaluation is completed, subjects who do not experience unacceptable 
toxicity, if the investigator judges that the benefit of continued treatment outweighs 


the risk, will enter the maintenance treatment period. In the maintenance treatment 
period, subjects will continue to receive one more dose of the investigational drug 
according to the DLT evaluation period dosing regimen (injection into the same lesion 
as the DLT evaluation period, tentatively with 1 injection on Day 1, the dosing 
regimen may be adjusted by the sponsor and investigator based on the PK 
characteristics of this study), and safety assessments will be performed on Day 7, Day 
14, and Day 21 after dosing. Samples will be collected at the predetermined 
timepoints according to the study flow chart. 
Follow-up Period: Safety follow-up until 28 days after the last dose. 
 
Dose Escalation 
This study will enroll patients with advanced solid tumors and use the traditional "3+3 
method" for dose escalation. The dose escalation principle is: in any dose cohort, 3 
subjects will be enrolled first. If none of the first 3 subjects experience DLT during the 
DLT evaluation period, the next dose cohort can be entered. If ≥2 of the first 3 
subjects experience DLT during the DLT evaluation period, dose escalation will be 
stopped (for the 30 mg cohort, if 2 DLTs occur, the sponsor and investigator will 
jointly decide whether to reduce the dose and continue exploration). If 1 of the first 3 
subjects experiences DLT during the DLT evaluation period, an additional 3 subjects 
will be enrolled in that dose cohort, and if ≤1 of the 6 subjects in that dose cohort 
experience DLT during the DLT evaluation period, the next dose cohort can be 
entered; if ≥2 of the 6 subjects in that dose cohort experience DLT during the DLT 


evaluation period, dose escalation will be stopped. The dose prior to the dose at which 
≥2/3 or ≥2/6 subjects experience DLT during the DLT evaluation period will be 
determined as the MTD (if only 3 subjects are enrolled in a cohort, an additional 3 
subjects will need to be enrolled). 
The “3+3” dose escalation principle 
The number of subjects who 
experienced a dose-limiting 
toxicity (DLT) within a particular 
dose cohort 
dose escalation principle 
0/3 
no DLT is observed in the 3 newly enrolled subjects 
0/3 
no DLT is observed in the 3 newly enrolled subjects 
≥2/3 
Dose escalation should be stopped, and that dose will be 
considered the Maximum Administered Dose (MAD). If the 
previous lower dose was only administered to 3 subjects, 
then 3 more subjects need to be enrolled 
1/3 
If the 3 newly enrolled subjects in the dose group do not 
erience a DLT (Dose-Limiting Toxicity), then the study will 
ceed to the next dose group. 
  
 If ≥1 of the 3 newly enrolled subjects in the dose group 
experience a DLT, then dose escalation will be 
stopped, and that dose level will be considered the 
MAD (Maximum Administered Dose). The previous 
dose level will be considered the MTD (Maximum 
Tolerated Dose) (if the dose group only had 3 
subjects, then an additional 3 subjects will need to 
be enrolled). 
 
The DLT (Dose-Limiting Toxicity) evaluation period is in the first cycle, i.e., within 
21 days after the first dose. This stage is tentatively set with 3 dose groups (calculated 
as Fe2+, 30 mg, 60 mg, 90 mg). If ≥2 subjects in the 90 mg group observe DLT, the 
dose will be reduced to 75 mg for safety and tolerability observation; if the dose is 
increased to 90 mg and MTD (Maximum Tolerated Dose) is still not reached, the SRC 


(Safety Review Committee) will discuss continuing to escalate the dose to 120 mg, 
150 mg, or even higher (if MTD is still not reached at 120 mg, the SRC will discuss 
whether to stop dose escalation or directly proceed to 150 mg or even higher doses). 
 
After 3-6 subjects in each dose group have completed the DLT evaluation, the SRC 
will evaluate the overall safety of each dose group based on the data obtained and 
determine whether to continue escalating to the next dose group or to determine the 
recommended dose for subsequent clinical development. 
 
Enrollment Interval: To fully protect the safety of the subjects, during the dose 
escalation process, the first subject in each dose group must be dosed at least 3 days 
after the first dose, and the remaining subjects in that dose group can then start the 
first dose. The interval for subsequent subjects in the same dose group can be 
controlled at the discretion of the investigator. The last subject in each dose group 
must complete the DLT evaluation, and the safety and tolerability must be reviewed 
by the SRC before the first subject in the next dose group can receive the first dose. 
 
Subject Replacement: During the DLT evaluation period, if a subject is unable to be 
evaluated for DLT (e.g., the subject's dose of the study drug did not reach at least 80% 
of the protocol-specified dose, or the subject discontinued study treatment before 
completing the DLT evaluation period for reasons other than DLT), additional 
subjects will need to be enrolled to make up the corresponding number in that dose 


group. 
 
DLT Definition: This study will grade toxicities according to NCI CTCAE v5.0. DLT 
refers to the following toxicity reactions that are considered by the investigator and/or 
the sponsor to be definitely or possibly related to the study drug CNSI-Fe, occurring 
within the first cycle (i.e., within 21 days after the first dose): 
 
Hematological toxicity: 
(1) Any grade 4 hematological toxicity; 
(2) Any grade 3 hematological toxicity that persists for >7 days after best supportive 
care, or grade 3 thrombocytopenia with bleeding tendency or requiring platelet 
transfusion; 
(3) Grade 3 neutropenia with fever, defined as: ANC<1×10^9/L and a single 
temperature >38.3°C or sustained temperature ≥38°C for >1 hour. 
 
Non-hematological toxicity: 
(1) Grade 3 cardiac toxicity that persists for >3 days after best supportive care, or 
grade 4 cardiac toxicity; 
(2) Grade 3 hepatic toxicity (for subjects with liver or bone metastases, and baseline 
grade 2 liver transaminases, ALT, AST or ALP >10×ULN) that persists for >3 days 
after best supportive care, or grade 4 hepatic toxicity; 
(3) Any grade 3 non-hematological toxicity (excluding laboratory tests) that persists 


for >7 days after best supportive care, except for grade 3 nausea, vomiting or diarrhea; 
(4) Any grade 4 non-hematological toxicity (excluding laboratory tests); 
(5) Any grade 3 or 4 non-hematological laboratory abnormality, if: 
 
It requires medical intervention; 
Or leads to hospitalization; 
Or persists at grade 3 or above for ≥7 days after drug discontinuation. 
Others: 
(1) Any grade 5 toxicity; 
(2) Other grade toxicities that the investigator and sponsor agree require early 
termination of CNSI-Fe treatment. 
This study will not only observe the safety and tolerability of CNSI-Fe, but also 
preliminarily evaluate the efficacy of CNSI-Fe in patients with advanced solid tumors. 
 
The investigators will evaluate the efficacy of CNSI-Fe based on the results of 
imaging examinations [computed tomography (CT), positron emission tomography 
(PET)/CT, or magnetic resonance imaging (MRI)], referring to the revised RECIST 
v1.1 and RECIST v1.1. 
 
Contrast-enhanced CT or contrast-enhanced MRI is the preferred imaging method for 
evaluating tumor response. If the subject is known to be allergic to the contrast agent, 
if possible, obtain a contrast agent evaluation using local preventive standards, or use 


alternative methods. In cases where contrast agents are strictly contraindicated, 
non-contrast scans should be performed. If the subject is contraindicated for 
contrast-enhanced CT scans, a non-contrast chest CT scan and contrast-enhanced 
abdominal and pelvic MRI scan can be performed. 
 
The baseline imaging evaluation will be performed within 28 days prior to the first 
study treatment (if the subject has undergone imaging examinations at the study site 
during the routine clinical care process prior to signing the ICF, and the examination 
site and method meet the protocol requirements, and the examination time is within 
28 days prior to the first study treatment, the corresponding examination results may 
be used for this trial's screening after the investigator's consent). 
 
All subjects will undergo tumor assessment once every 3-4 weeks during the study 
treatment period, and once every 7-8 weeks for those who enter the maintenance 
treatment period (the investigator may decide whether to perform additional imaging 
examinations for special changes in the disease condition, and the first tumor 
assessment must be performed at 3-4 weeks). 
 
Subjects who achieve a complete response (CR) or partial response (PR) in the first 
assessment will require confirmation at least 4 weeks later. 
 
The baseline tumor evaluation must include the chest, abdomen, pelvis, and head (to 


exclude brain metastases), as well as other suspected tumor sites. Subsequent 
evaluations should re-evaluate all measurable and evaluable lesions found at baseline, 
including the chest, abdomen, pelvis, and other suspected tumor sites. 
 
The imaging examination methods used for efficacy evaluation of subjects during the 
study period must be consistent with the baseline imaging evaluation methods. 
 
Investigational medicinal products 
The CNSI-Fe involved in this study is composed of a ferrous iron adsorbed carbon 
nanoparticle, which are prepared and used on-site. The drug information is as follows: 
Drug Name 
Dosage 
Form 
Specification 
Storage Conditions 
Shelf Life 
CNSI-Fe(II) 
Injection  
2 mL：100 mg 
Store at 2-8°C  
24 months 
Ferrous Sulfate 
for Injection 
Lyophilized  
Powder for 
Injection 
30 mg/vial (as 
ferrous) 
Store at 2-8°C, protected 
from light 
24 months 
 
The carbon nanoparticle suspension injection and the ferrous sulfate injection are both 
provided by the applicant. 
 
Packaging and labeling: The nano carbon suspension injection and the ferrous sulfate 
injection are labeled by the applicant according to the "Good Manufacturing Practice 
for Drugs (Revised in 2010)" (NMPA, 2011) and the "Good Clinical Practice for 
Drugs" (NMPA, 2020), and are marked as for clinical trial use only. 
 


 
dosage regimen 
Dose Escalation Phase (DLT Phase) 
 
Dosing 
Three dose groups are tentatively set (calculated as Fe2+, 30 mg, 60 mg, 90 mg). If ≥2 
subjects in the 90 mg group observe DLT, the dose will be reduced to 75 mg for safety 
and tolerability observation; if the dose is escalated to 90 mg and MTD is still not 
reached, the SRC will comprehensively discuss the available safety, tolerability, 
PK/PD, and preliminary efficacy data, and consider further dose escalation to 120 mg, 
150 mg, or even higher (if 120 mg still does not reach MTD, the SRC will discuss 
whether to stop dose escalation or directly proceed to 150 mg or even higher doses). 
Dosing Volume 
Regardless of tumor size, number, and location, a single tumor lesion suitable for 
intratumoral injection will be selected, and the corresponding dose of the 
investigational drug will be administered by intratumoral injection. The dosing 
volume will be determined based on the size of the injected lesion. If the 
corresponding dose of the investigational drug cannot be fully administered in one 
lesion, other lesions can be injected simultaneously. When multiple lesions are 
injected, the amount allocated to each lesion should be proportional to the lesion size, 
or the investigator can evaluate an appropriate allocation. 
During the study, the investigator may adjust the dosing regimen or add unplanned 


doses based on the safety, efficacy, and PK/PD data of CNSI-Fe. 
CNSI-Fe Preparation 
Take a vial of ferrous sulfate injection, keep the aluminum cap and rubber stopper 
sealed, and only remove the plastic outer cap of the aluminum-plastic combination 
cap. Use a suitable syringe to slowly draw an appropriate amount of the nano-carbon 
suspension injection, and inject it into the vial containing ferrous sulfate. Mix the 
solution evenly. The CNSI-Fe preparation requires aseptic operation, shielding from 
air, and must be used within 6 hours after preparation at room temperature. See 
Appendix 5 in Chapter 15 for details. 
Maintenance Treatment Period 
After the DLT assessment is completed, subjects who do not experience unacceptable 
toxicity, if the investigator judges that the benefit of continued treatment outweighs 
the risk, will enter the maintenance treatment period. During the maintenance 
treatment period, subjects will continue to receive the investigational drug according 
to the DLT assessment regimen (tentatively, one intratumoral injection on Day 1, the 
dosing regimen may be adjusted based on the PK characteristics of this study, as 
discussed by the sponsor and investigator). 
 
Dose Groups: Three dose groups are tentatively set, namely 30 mg, 60 mg, and 90 
mg (calculated as Fe2+). Subsequently, based on the safety, tolerability, PK/PD, and 
preliminary efficacy data of CNSI-Fe, additional doses may be added for further 
investigation. 


 
 
Research Steps: Please refer to the experimental process flow chart 
 
Sample collection: PK and PD studies will be conducted by a designated third-party 
laboratory. The sampling time points for each sample may be adjusted based on the 
results of the previous clinical studies (decided by the SRC discussion). The methods 
for sample collection, processing, preservation, transportation, and testing will be 
described in a separate laboratory operations manual. 
 
PK samples 
First cycle: Within 1 hour before CNSI-Fe dosing, 5 min ± 1 min, 10 min ± 2 min, 15 
min ± 2 min, 30 min ± 5 min, 1 h ± 10 min, 2 h ± 10 min, 4 h ± 15 min, 8 h ± 15 min, 
12 h ± 30 min, 24 h ± 30 min, 48 h ± 1 h, 72 h ± 2 h after CNSI-Fe dosing. 
Second cycle (if any): The sampling time points may be adjusted appropriately based 
on the PK results from the first cycle (adjusting sampling time, increasing/decreasing 
sampling frequency, etc.). 
Collect 3 mL of blood sample at each sampling point. 
 
PD samples (exploratory tumor tissue samples) 
Before the first CNSI-Fe dose, 24 h to 17 days after the first CNSI-Fe dose (specific 
time points to be determined based on clinical practice), and at disease progression. 


Subject to the subject's willingness, try to collect tumor tissue samples from the 
injected lesion before and after the first CNSI-Fe dose; the pre-dose tumor tissue 
sample can be the most recent archived sample or the sample collected during the 
screening period; post-dose tumor tissue samples will be collected according to 
clinical practice. 
 
Tumor PK samples (exploratory tumor tissue samples) 
Before the first CNSI-Fe dose, within 21 days after the first CNSI-Fe dose (specific 
time points to be determined based on clinical practice). 
Subject to the subject's willingness, try to collect tumor tissue samples from the 
injected lesion before and after the first CNSI-Fe dose; the pre-dose tumor tissue 
sample can be the most recent archived sample or the sample collected during the 
screening period; post-dose tumor tissue samples will be collected according to 
clinical practice as much as possible to complete the tumor PK study (not a mandatory 
requirement). 
 
Statistical Analysis: Analysis of the Data Set 
Full Analysis Set (FAS) 
The FAS includes all enrolled subjects who received at least one dose of the study 
drug and had a measurable lesion at baseline. 
 
Dose-Limiting Toxicity (DLT) Analysis Set (DLTS) 


The DLTS includes subjects who completed the DLT evaluation period as per the 
protocol (defined as receiving at least one dose of the study drug at ≥80% of the 
protocol-specified dose and did not prematurely discontinue or experience a DLT 
during the DLT evaluation period). 
 
Safety Analysis Set (SS) 
The SS includes all subjects who received at least one dose of the study drug and had 
at least one post-dose safety assessment. 
 
Pharmacokinetic (PK) Analysis Set (PKS) 
The PKS includes all subjects who received at least one dose of the study drug and 
had at least one valid PK measurement. 
 
Pharmacodynamic (PD) Analysis Set (PDS) 
The PDS includes all subjects who received at least one dose of the study drug and 
had at least one valid PD endpoint measurement. 
 
Statistical Analysis Methods 
The Statistical Analysis Plan (SAP) will provide detailed specifications and 
descriptions of all planned statistical analyses in accordance with the protocol, and 
will be finalized prior to database lock. 
 


The statistical analyses will include demographic and baseline characteristics, safety 
and tolerability, PK, PD, and efficacy. 
 
The analyses will be primarily descriptive, without formal statistical hypothesis 
testing. 
 
The statistical analyses will be performed using SAS® version 9.4 or higher. 
 
The following descriptive statistical analyses will be conducted based on the nature of 
the variables: 
 
Continuous variables: number of non-missing observations, mean and standard 
deviation (SD), median, minimum, and maximum. 
Categorical variables: frequency and percentage. 
Safety Analysis: For the primary estimand, the number of subjects, incidence, and 
number of events of each type of adverse event will be summarized by dose group. 
Numerical laboratory data at each visit will be described using mean, SD, median, 
extremes, and changes from baseline, and categorized as normal, clinically 
insignificant abnormal, or clinically significant abnormal, with the incidence of 
clinically significant abnormalities tabulated. The same approach will be used for 
ECG. Vital signs will be described using mean ± SD. 
For the secondary estimand, the incidence of DLTs will be summarized by dose 


group. 
 
PK Analysis: The primary PK endpoints for CNSI-Fe intratumoral injection will 
include the iron ion concentration in serum. PK analyses will provide descriptive 
statistics of the relevant measurements and concentration-time profiles. For the first 
dose of CNSI-Fe, AUC, Cmax, Tmax, and other parameters may be calculated. 
Descriptive statistics will be provided for these parameters, and informal testing of 
AUC may be performed to explore the relationship with dose. 
 
Efficacy Analysis: Based on best lesion response, ORR, DCR, and their two-sided 
95% confidence intervals (Clopper-Pearson method) will be statistically described. 
 
PD Analysis: Descriptive statistics will be provided for the PD endpoint levels before 
and after dosing, as well as the changes (absolute or percent) from baseline. 
Corresponding time course profiles will be generated. Comparisons of the PD 
endpoint levels and changes from baseline at each timepoint will be performed, with 
normality testing and using paired t-tests or Wilcoxon signed-rank tests as 
appropriate. 
 
 
Research on time： 
After this study has been reviewed and approved by the Ethics Committee (EC), it 


will continue until the expected sample size is reached, based on the actual situation. 
 
The study is expected to end 28 days after the last participant receives a maximum of 
two doses. For participants who still achieve CR (complete response) or PR (partial 
response) at the end of the study, if the investigator determines that they can still 
benefit from continued treatment, they can receive the study drug free of charge until 
disease progression, development of intolerable toxicity, the investigator determines it 
is no longer appropriate for the participant to continue receiving the study drug, or the 
sponsor terminates the study.


Table 1-1. Clinical Trial Flow Diagram 
Study Procedure 
Screening 
Period1 
Therapeutic Period（DLT Evaluation 
Period）2 
Maintenance Therapy Phase（Secondary 
Cycle）3 
Early 
Termination/E
arly 
Completion of 
Treatment 
Visits 4 
Safety 
Follow-up 5 
 
 
DLT Evaluation Period 
Secondary Cycle（if tolerated, 21 
days/cycle） 
 
 
follow-up visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
 
V10 
date（D） 
D-28~D-1 
D1 
D7 
D14 
D21 
D1 
D7 
D14 
D21 
confirm 
end/termination 
of treatment 
28 days 
after the 
last 
administrat
ion 
period（d） 
 
 
±1d 
±1d 
±1d 
+7d 
±1d 
±1d 
±1d 
+7 d 
±3 d 
Research 
management process 
 
 
 
 
 
 
 
 
 
 
 
informed consent 
× 
 
 
 
 
 
 
 
 
 
 
evaluation 
of 
inclusion 
and 
exclusion criteria 
× 
 
 
 
 
 
 
 
 
 
 
demographic data 
× 
 
 
 
 
 
 
 
 
 
 
medical 
history 
and 
treatment history 6 
× 
 
 
 
 
 
 
 
 
 
 
Clinical 
procedures/evaluatio
ns 
 
 
 
 
 
 
 
 
 
 
 


vital signs 7 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
physical examination 8 
× 
× 
Based on clinical indications, 
determined by the researcher 
× 
Determined by the researcher 
based on clinical indications 
× 
× 
weight9 
× 
× 
 
 
 
× 
 
 
 
× 
× 
height 
× 
 
 
 
 
 
 
 
 
 
 
ECOG 
×10 
× 
 
 
× 
× 
 
 
× 
× 
× 
12-lead ECG 11 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
echocardiogram 12 
× 
Determine and conduct based on clinical indications as judged by the investigator throughout 
the study period 
 
 
combination therapy 
13 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Adverse envents14 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Laboratory 
procedures/evaluatio
ns 
 
 
 
 
 
 
 
 
 
 
 
complete blood count 
15 
×10 
 
× 
× 
× 
 
× 
× 
× 
× 
× 
urinalysis 16 
×10 
 
× 
× 
× 
 
× 
× 
× 
× 
× 
blood biochemistry 17 
×10 
 
× 
× 
× 
 
× 
× 
× 
× 
× 
coagulation function 
18 
×10 
 
× 
 
× 
 
× 
 
× 
× 
× 
pregnancy test 19 
×10 
 
 
 
 
 
 
 
 
× 
× 
FSH20 
× 
 
 
 
 
 
 
 
 
 
 
glucose-6-phosphate 
dehydrogenase 
(G6PD) test 
× 
 
 
 
 
 
 
 
 
 
 
viral serology 21 
× 
 
 
 
 
 
 
 
 
 
 
blood iron test 22 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 


tumor markers 23 
×10 
 
 
 
× 
 
 
 
× 
× 
× 
cardiac 
enzyme 
profile 24 
× 
During the entire study period, decisions were made by the researchers based on clinical 
indications 
 
 
Investigational drug 
 
 
 
 
 
 
 
 
 
 
 
CNSI-Fe 
 
× 
 
 
 
× 
 
 
 
 
 
PK/PD 
 
 
 
 
 
 
 
 
 
 
 
PK sampling 25 
 
× 
 
 
 
× 
 
 
 
 
 
collection of tumor 
tissue 
samples 
(PD/intra-tumoral PK 
sampling)26 
× 
× 
 
 
Efficacy evaluation 
 
 
 
 
 
 
 
 
 
 
 
tumor assessment 27 
× 
× 
× 
 


Note: Unless otherwise specified, all assessments, examinations, and sample 
collections should be performed on the same day before drug administration. 
 
Screening Period: Routine examinations or examination results obtained at a tertiary 
hospital (or this hospital) within 28 days prior to the first dose (unless otherwise 
specified) and before signing the informed consent form (ICF) can be used for 
screening, and do not need to be repeated. 
 
Treatment Period (DLT Evaluation Period): For the first intratumoral injection of 
CNSI-Fe, safety assessments will be performed on Day 7 (±1 day), Day 14 (±1 day), 
and Day 21 (±1 day) after the first dose to evaluate DLT. 
 
Maintenance Treatment Period: After the DLT evaluation is completed, subjects 
without unacceptable toxicity will continue to the maintenance treatment period if the 
investigator determines that the benefit of continued treatment outweighs the risk. 
During the maintenance treatment period, subjects will receive one more dose of the 
investigational drug (intratumoral injection to the lesion, tentatively scheduled for 
Day 1, the dosing regimen may be adjusted based on the PK characteristics of this 
study by the sponsor and investigator). 
 
Early Termination/End of Treatment (EOT) Visit: This will be scheduled within 7 
days after the decision to discontinue treatment. If the assessments required for the 


EOT visit were performed within 7 days prior to the EOT visit, they do not need to be 
repeated. 
 
Safety Follow-up: Subjects who have received at least one dose of the study drug will 
undergo a safety visit 28 days (±3 days) after the last dose. If the assessments required 
for the safety visit were performed within 3 days prior to the safety visit, they do not 
need to be repeated. 
 
Medical History and Treatment History: Collected during the screening period, 
including past medical history, medication history (concomitant treatments within 4 
weeks prior to screening and currently ongoing), history of all previous tumors 
(including tumor stage, diagnosis date, genetic test results), history of all previous 
anti-tumor treatments, family history, surgical history, immunization history, allergy 
history, smoking history, alcohol history, history of drug abuse/dependence, etc. 
 
Vital Signs: Including respiratory rate, pulse/heart rate, blood pressure, and body 
temperature. Measured during screening, within 2 hours before CNSI-Fe 
administration, 1.5 hours (±30 minutes) after administration, on Days 7, 14, and 21 of 
each cycle, at the End of Treatment (EOT) visit, and during the safety follow-up visit 
(excluding telephone visits). 
 
Physical Examination: Including general condition, skin and mucosa, lymph nodes, 


head, neck, chest, abdomen, spine, limbs, and nervous system. A complete physical 
examination will be performed during screening, before CNSI-Fe administration, at 
the EOT visit, and during the safety follow-up visit (excluding telephone visits). 
Symptom-directed physical examinations will be performed during the treatment 
period as clinically indicated. 
 
Body Weight: Measured during screening and before CNSI-Fe administration. 
 
ECOG performance status, complete blood count, urinalysis, blood chemistry, 
coagulation function, pregnancy test (for women of childbearing potential), and tumor 
marker tests should be completed within 7 days prior to the first dose of the 
investigational drug. 
 
12-lead ECG: Performed during screening, within 2 hours before CNSI-Fe 
administration, 0.5 hours (±5 minutes), 4 hours (±30 minutes), 8 hours (±30 minutes), 
24 hours (±30 minutes), 48 hours (±30 minutes), and 72 hours (±30 minutes) after 
administration, on Days 7, 14, and 21 of each cycle, at the EOT visit, and during the 
safety follow-up visit (excluding telephone visits). Continuous cardiac monitoring 
will also be performed for 8 hours after CNSI-Fe administration. Additional 12-lead 
ECG assessments may be added during the study to ensure subject safety, at the 
discretion of the investigator. 
 


Echocardiography: Left ventricular ejection fraction (LVEF). Performed during 
screening, and as needed during the study period if there are clinically significant 
ECG abnormalities. 
 
Concomitant Medications: All concomitant medications and treatments from the 
time of ICF signing until 28 days after the last dose or the start of a new anti-cancer 
therapy (whichever occurs first) should be recorded in the patient's medical records 
and reported in the electronic case report form (eCRF), including the name, reason for 
use, dose, route of administration, frequency, start date, and stop date. 
 
Adverse Events (AEs): Only serious adverse events (SAEs) related to the 
protocol-specified procedures should be reported before the start of study drug 
treatment. After the start of study treatment, all AEs should be reported, regardless of 
their relationship to the study drug, until 28 days after the last dose. The investigator 
should follow up on all AEs until the event resolves to baseline or better, is considered 
stable by the investigator, the subject is lost to follow-up, or the subject withdraws 
consent. For all SAEs related to the investigational product or study procedures, every 
effort should be made to follow up until a final outcome can be reported. 
 
Blood routine: Red blood cell count (RBC), hemoglobin (Hb), hematocrit, white 
blood cell count (WBC) and differential count (neutrophils, eosinophils, lymphocytes, 
monocytes, basophils and others) and platelet count (PLT). To be performed within 7 


days prior to first dose of study drug in the screening period, on Day 7, Day 14, Day 
21 of each cycle, at the End of Treatment (EOT) visit, and at the safety follow-up visit 
(excluding telephone visits). Additional blood routine tests can be performed as 
needed based on the investigator's clinical judgment. 
 
Urinalysis: Urine specific gravity, urine pH, urine glucose, urine protein, urine ketone, 
urine red blood cells and urine white blood cells. To be performed within 7 days prior 
to first dose of study drug in the screening period, on Day 7, Day 14, Day 21 of each 
cycle, at the EOT visit, and at the safety follow-up visit (excluding telephone visits). 
 
Biochemistry: Glucose, blood urea nitrogen (BUN) or urea, creatinine (Cr), sodium, 
potassium, magnesium, chloride, calcium, phosphorus, total bilirubin (TBIL), alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase 
(ALP), lactate dehydrogenase (LDH), total protein, albumin, triglycerides, total 
cholesterol, amylase, lipase. To be performed within 7 days prior to first dose of study 
drug in the screening period, on Day 7, Day 14, Day 21 of each cycle, at the EOT visit, 
and at the safety follow-up visit (excluding telephone visits). Additional biochemistry 
tests can be performed as needed based on the investigator's clinical judgment. 
 
Coagulation function: International normalized ratio (INR), prothrombin time (PT), 
activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen (FIB). 
To be performed within 7 days prior to first dose of study drug in the screening period, 


on Day 7, Day 21 of each cycle, at the EOT visit, and at the safety follow-up visit 
(excluding telephone visits). 
 
Pregnancy test: For female subjects of childbearing potential only; to be performed 
within 7 days prior to first dose of study drug in the screening period, at the EOT visit, 
and at the safety follow-up visit (excluding telephone visits). Pregnancy tests other 
than screening can be either serum or urine pregnancy tests, as per the investigator's 
judgment. If a urine pregnancy test is positive, it must be confirmed by a serum 
pregnancy test. 
 
FSH test: For post-menopausal female subjects over 45 years of age but less than 55 
years of age (see Section 4.1), a serum FSH test will be performed during the 
screening period to confirm post-menopausal status. If the subject is confirmed to be 
post-menopausal, no further pregnancy testing will be required; otherwise, she will 
undergo pregnancy testing like female subjects of childbearing potential. 
 
Viral serology: Including hepatitis B virus (HBV) - [hepatitis B surface antigen 
(HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), 
hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb)], hepatitis C virus 
(HCV) - [HCV-Ab] and human immunodeficiency virus (HIV) - [Anti-HIV] testing. 
HBV quantitative requirement: During screening, test the 5 HBV markers, if HBsAg 
is positive, HBV DNA testing is required; if HBsAg is negative but HBcAb is positive, 


HBV DNA testing is also required. HCV quantitative requirement: During screening, 
test for HCV-Ab to determine if the subject has HCV infection, if HCV-Ab is positive, 
HCV RNA quantitative testing is required. 
 
Iron tests: Serum iron (Fe), total iron binding capacity (TIBC), serum ferritin (SF), 
transferrin saturation (TSAT). To be performed during screening, within 24 h prior to 
CNSI-Fe dosing, at 5 min ± 1 min, 15 min ± 2 min, 30 min ± 5 min, 2 h ± 30 min, 6 h 
± 30 min and 10 h ± 30 min post-dosing, on Day 7, Day 14, Day 21 of each cycle, at 
the EOT visit, and at the safety follow-up visit (excluding telephone visits). 
Additional iron tests may be performed as needed for subject safety during the study. 
 
Tumor marker detection: carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), 
cancer antigen 125 (CA125), cancer antigen 15-3 (CA15-3), cancer antigen 19-9 
(CA19-9), etc. Researchers will select appropriate tumor markers based on the 
situation. These will be tested within 7 days before the first dose of the study drug, on 
Day 21 of each cycle, at the End of Treatment (EOT) visit, and during the safety 
follow-up (excluding telephone visits). 
 
Cardiac enzymes: lactate dehydrogenase (LDH), creatine kinase (CK), creatine 
kinase-MB 
(CK-MB), 
aspartate 
aminotransferase 
(AST), 
hydroxybutyrate 
dehydrogenase (HBDH). These will be tested during the screening period, and 
supplementary testing will be performed during the study period if the subject 


experiences chest pain, palpitations, or ECG abnormalities. 
PK blood sample collection: In Cycle 1: within 1 hour before CNSI-Fe dosing, and at 
5 min ± 1 min, 10 min ± 2 min, 15 min ± 2 min, 30 min ± 5 min, 1 h ± 10 min, 2 h ± 
10 min, 4 h ± 15 min, 8 h ± 15 min, 12 h ± 30 min, 24 h ± 30 min, 48 h ± 1 h, and 72 
h ± 2 h after dosing. In Cycle 2 (if applicable), the sampling schedule may be adjusted 
based on the PK results from Cycle 1. 
 
Collection of tumor tissue samples (PD/intratumoral PK sampling): For subjects 
who consent to provide archived or fresh tumor tissue samples from the target lesion, 
the samples will be obtained during the screening period. For PD samples, they should 
be collected within 24 hours to 17 days after the first dose (specific timepoint to be 
determined based on clinical practice), and at disease progression as clinically 
indicated. For intratumoral PK samples, they should be collected within 21 days after 
the first dose (specific timepoint to be determined based on clinical practice). Tumor 
tissue samples will only be transported for subjects who are eligible for enrollment. 
Tumor assessment: Baseline imaging assessments will be performed within 28 days 
prior to the first study treatment (if the patient underwent imaging as part of routine 
clinical care prior to signing the ICF, and the imaging modality and location meet the 
protocol requirements, the results may be used for screening upon investigator 
approval). Baseline tumor evaluation should include the chest, abdomen, pelvis, head 
(to exclude brain metastases), and any other suspected tumor sites. Subsequent 
evaluations should re-assess all measurable and evaluable lesions identified at 


baseline, including the chest, abdomen, pelvis, and any other suspected tumor sites. 
The imaging modality used for tumor assessment during the study must be consistent 
with the baseline assessment. Subjects will undergo tumor assessment every 3-4 
weeks during the treatment period, and every 7-8 weeks during the maintenance 
period (the investigator may decide to perform additional imaging assessments based 
on changes in the subject's condition; the first tumor assessment must be performed at 
weeks 3-4). Subjects with a confirmed complete response (CR) or partial response 
(PR) at the first assessment will require confirmation at least 4 weeks later. Tumor 
imaging may be omitted at the early termination/withdrawal visit if it was performed 
within th 

ICF_001.pdf: 
A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic 
(PK) Characteristics, and Preliminary Efficacy of Intratumoral Injection of 
Ferrous Ion Adsorbed Carbon Nanoparticle Suspension Injection (CNSI-Fe) in 
Patients with Advanced Solid Tumors 
 
Informed Consent Form 
NCT06048367 
 
Version/Date: V3.2/March 28, 2024 
 
 
Protocol Number: YR-2021-01-CNSI-Fe 
 
Screening Number: 
 
Investigator: Yongsheng Wang 
 
Clinical Trial Institution: West China Hospital, Sichuan University 
 
Trial Site Address: No. 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province 
 
Sponsor: Sichuan Enray Pharmaceutical Technology Company 


Informed Consent Form · Information Page 
Please read the following content carefully and ensure that you fully understand 
this consent form before signing on the last page! 
 
[Introduction to the Informed Consent Form] 
We invite you to participate in a Phase I clinical study of Ferrous Ion Adsorbed 
Carbon Nanoparticle Suspension Injection (CNSI-Fe) in patients with advanced solid 
tumors, initiated by Sichuan Enray Pharmaceutical Technology Company. Based on 
your current condition, you may be eligible to participate in this clinical research. We 
will provide you with some important information for your reference. 
This study will be conducted at West China Hospital, Sichuan University. Before 
you decide whether to participate in this study, please read the following content 
carefully to help you understand the purpose of this study, the aspects it involves, as 
well as the potential benefits, risks, and discomforts you may experience if you decide 
to participate. You also have the right to voluntarily participate in or withdraw from 
the trial at any time. If you have any questions or need more information during the 
reading process, please feel free to contact the investigator, who will answer any 
questions you may have. 
Your participation in this clinical study is entirely voluntary. The investigator 
will provide you with detailed information about the content of this trial and interpret 
this Informed Consent Form together with you. If, after careful consideration, you 
agree to participate in the trial, please sign the informed consent form, and you will 


receive a copy of the form with the investigator's signature. 
 
[Study Overview] 
Ferrous Ion Adsorbed Carbon Nanoparticle Suspension Injection (CNSI-Fe) is an 
innovative anticancer drug developed by Sichuan Enray Pharmaceutical Technology 
Company, which is a nanosuspension formulation with iron ions as the active 
pharmaceutical ingredient. After the iron ions in CNSI-Fe enter cancer cells, a series 
of chemical reactions occur, affecting the membrane function of tumor cells, leading 
to cancer cell death, thereby achieving the therapeutic effect on malignant tumors. 
This study, titled "Phase I clinical study to evaluate the safety, tolerability, 
pharmacokinetic (PK) characteristics, and preliminary efficacy of intratumoral 
injection of Ferrous Ion Adsorbed Carbon Nanoparticle Suspension Injection 
(CNSI-Fe) in patients with advanced solid tumors," is led by West China Hospital, 
Sichuan University, with Professor Yongsheng Wang as the principal investigator. It is 
the first study of CNSI-Fe in the Chinese population with solid tumors and aims to 
provide new and important clinical treatment options for patients with advanced solid 
tumors. 
This study has been approved by the National Medical Products Administration 
and will be conducted at 3 to 6 research centers nationwide, with approximately 15 to 
30 patients enrolled. 
This study has been approved by the Clinical Trial Ethics Committee of West 
China Hospital, Sichuan University, and will be conducted at West China Hospital. 


 
[Study Objectives] 
The main objective of this study is to evaluate the safety and tolerability of 
intratumoral injection of Ferrous Ion Adsorbed Carbon Nanoparticle Suspension 
Injection (CNSI-Fe) at different doses in patients with advanced solid tumors. It aims 
to observe dose-limiting toxicity (DLT) of CNSI-Fe and determine the maximum 
tolerated dose (MTD) or the highest injectable dose in humans as a basis for dose 
selection in subsequent clinical studies. The secondary objectives are to evaluate the 
pharmacokinetic (PK) characteristics of CNSI-Fe at different doses and to 
preliminarily assess the efficacy of CNSI-Fe in patients with advanced solid tumors. 
The exploratory objectives are to evaluate the intratumoral pharmacodynamics (PD) 
characteristics of CNSI-Fe at different doses (not mandatory), to evaluate the 
intratumoral PK characteristics of CNSI-Fe in patients with advanced solid tumors 
(not mandatory), and to explore the dose-response relationship between tumor size 
and CNSI-Fe injection dose/concentration (not mandatory). 
 
[Inclusion Criteria] You need to meet all the following criteria to be eligible for 
this trial: 
1. Understand and voluntarily sign the written informed consent form (ICF) and be 
willing and able to comply with all trial requirements. 
2. Be a male or female aged 18 to 80 years (inclusive) at the time of signing the ICF. 
3. Have a histologically or cytologically confirmed advanced solid tumor, and the 


current standard treatment is ineffective (disease progression after treatment or 
inability to tolerate treatment) or there is no effective standard treatment available, 
such as colorectal cancer, pancreatic cancer, breast cancer, stomach cancer, cervical 
cancer, lung cancer, head and neck cancer, bile duct cancer, kidney cancer, prostate 
cancer, vulvar cancer, etc. 
Note: Late-stage solid tumor patients who cannot receive standard treatment for any 
reason, or patients with tumor types that are insensitive to existing standard treatments 
(such as pancreatic cancer, undifferentiated thyroid cancer, and sarcoma), and who 
experience disease progression after receiving standard treatment for the first time are 
allowed to participate. 
4. According to RECIST v1.1, there must be at least one measurable lesion that has 
not been previously undergone radiation therapy (unless the lesion has clearly 
progressed after radiation therapy) and has not undergone tissue biopsy within 7 days 
prior to the first dose. 
5. The presence of injectable lesions (able to be directly injected or assisted by 
medical imaging instruments). 
6. ECOG performance status of 0-1 within 7 days prior to the first dose. 
7. Expected survival of ≥12 weeks. 
8. Adverse drug reactions (ADR) caused by previous treatments have recovered to 
grade 1 or below according to the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) v5.0 standards, excluding 
alopecia. 


9. Left ventricular ejection fraction (LVEF) ≥50%. 
10. Adequate hematological and organ function within 7 days prior to the first dose, 
with laboratory test results meeting the following criteria: 
a) Hematology: 
Absolute neutrophil count (ANC) ≥1.5×10^9/L without the use of granulocyte 
colony-stimulating factor (G-CSF) within 14 days prior to the hematological 
laboratory test. 
Platelet count (PLT) ≥90×10^9/L without platelet transfusion within 14 days prior 
to the hematological laboratory test. 
Hemoglobin (Hb) ≥90 g/L without blood transfusion or use of erythropoietin within 
14 days prior to the hematological laboratory test. 
b) Renal function: 
Serum creatinine (Cr) ≤1.5 times the upper limit of normal (ULN) or calculated 
creatinine clearance (Ccr) ≥50 mL/min using the Cockcroft-Gault formula 
(calculated only when baseline Cr >1.5 times ULN). 
c) Liver function: 
Total bilirubin (TBIL) ≤1.5 times ULN (≤3.0 times ULN for patients with Gilbert's 
syndrome or liver metastasis). 
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline 
phosphatase (ALP) ≤3 times ULN. Patients with confirmed liver metastasis or bone 
metastasis must meet the following conditions: 
Patients with confirmed liver metastasis: AST and ALT ≤5 times ULN. 


Patients with confirmed bone metastasis: ALP ≤5 times ULN. 
Serum albumin ≥2.8 g/dL. 
d) Coagulation function: 
International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial 
Thromboplastin Time (aPTT) ≤1.5×ULN; 
Note: If the injection site is in the skin and/or subcutaneous tissue and the patient is 
receiving anticoagulant therapy, it is allowed for INR, PT, and aPTT to be prolonged, 
as excessive bleeding can be controlled by applying direct pressure, as determined by 
the investigator. 
11. Women of childbearing potential (WOCBP) must have a negative pregnancy test 
result within 7 days prior to the first dose of the investigational drug and must commit 
to using effective contraception or abstinence during the study drug treatment period 
and for 6 months after the end of the study drug treatment. In addition, female patients 
must be non-lactating and agree not to donate eggs during this period; 
Note: WOCBP is defined as non-sterilized women who have experienced menarche 
but have not undergone sterilization procedures (hysterectomy or bilateral 
oophorectomy) and are not in the postmenopausal period. Postmenopausal is defined 
as continuous amenorrhea for ≥12 months in a woman over 45 years of age in the 
absence of other biological or physiological reasons. In addition, women under 55 
years of age must have serum follicle-stimulating hormone (FSH) levels >40 mIU/mL 
to confirm postmenopausal status. Hormone replacement therapy (HRT) may 
artificially suppress FSH levels in women and may require a washout period to return 


t o p h ysi ol o gical F S H le vels. T he d urati o n of t he was h o ut peri o d is o ne of t he fact ors 
i nfl ue nce d  b y  t he  t y pe  of  H R T.  T he  f oll o wi n g  was h o ut  peri o d  d urati o ns  are  
rec o m me n de d as g ui deli nes, a n d t he i n vesti gat or s h o ul d j u d ge t he res ults of ser u m 
F S H le vel testi n g:  
Va gi nal h or m o ne pre p arati o ns: at least 1 wee k (ri n g, crea m, gel); 
Tra ns der mal pre p arati o ns: at least 4 wee ks;  
Oral pre p arati o ns: at least 8 wee ks;  
Ot her gastr oi ntesti nal pre par ati o ns ma y re q uire a was h o ut peri o d of u p t o 6 m o nt hs. 
If t he ser u m F S H le vel is > 4 0 mI U/ m L d uri n g t he was h o ut peri o d, t he w o ma n ca n be 
c o nsi dere d p ost me n o pa usal. 
1 2. Male patie nts m ust c o m mit t o usi n g effecti ve c o ntrace pti o n or a bsti ne nce d uri n g 
t he st u d y dr u g treat me nt peri o d a n d f or 6 m o nt hs after t he e n d of t he st u d y dr u g 
treat me nt. I n a d diti o n, male patie nts m ust a gree n ot t o d o nate s per m. 
 
[E xcl usi o n Criteri a ] Yo u are n ot eli gi ble t o p artici p ate i n t his tri al if y o u meet 
a n y of t he f oll o wi n g c o n diti o ns: 
1. Hist or y or c urre nt prese nce of ir o n meta b olis m dis or ders (e xce pt f or patie nts wit h 
ir o n  deficie n c y  a n e mia),  s uc h  as  t halasse mia,  fa vis m  ( gl uc ose- 6- p h os p hate 
de h y dr o ge nas e deficie nc y), etc. 
2. Hist or y or c urr e nt pres e nce of si g ns of ca vit y or ga n perf orati o n at t he i nj ecti o n site. 
3. Hist or y or c urre nt pr es e nce of l ocal s ki n brea k d o w n, re d ness, n ecr osis, blee di n g, or 
a n y ot her c o n diti o n t hat ma y affect t he i njecti o n of t he i n vesti gati o nal dr u g at t he 


injection site. 
4. Target lesions have received radiotherapy or any other anti-tumor drug treatment 
within 4 weeks prior to the first administration of the investigational drug, or the time 
since the last anti-tumor treatment [including but not limited to chemotherapy, 
targeted therapy, immunotherapy, National Medical Products Administration (NMPA) 
approved anti-tumor traditional Chinese medicine, and Chinese herbal medicine with 
anti-tumor effects] has not reached 5 half-lives, whichever is shorter. 
5. Major surgery or significant trauma (excluding diagnostic procedures) or unhealed 
wounds and ulcers within the past 4 weeks prior to the first administration of the 
investigational drug. 
6. Presence of life-threatening clinical manifestations of brain and central nervous 
system metastasis at the time of enrollment. 
7. Poorly controlled hypertension (systolic blood pressure ≥150 mmHg or diastolic 
blood pressure ≥100 mmHg). 
8. Uncontrolled tumor-related pain. 
9. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated 
drainage (once/month or more frequently); 
10. Presence of other malignant tumors within 5 years prior to the initiation of the 
study treatment, except for non-melanoma skin cancer, localized prostate cancer, 
ductal carcinoma in situ, stage I uterine cancer, cervical carcinoma in situ, or breast 
carcinoma in situ that has already received curative treatment; 
11. Vaccination with live virus vaccines within 4 weeks prior to the initiation of the 


study treatment; 
Note: Injectable seasonal influenza vaccines are usually inactivated influenza 
vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are 
live attenuated vaccines and are not allowed. 
12. History of immunodeficiency, including human immunodeficiency virus (HIV) 
positive status or acquired/congenital immunodeficiency diseases, or history of organ 
transplantation; 
13. Active hepatitis B virus (HBV) infection [positive for hepatitis B surface antigen 
(HBsAg) or hepatitis B core antibody (HBcAb) and HBV deoxyribonucleic acid 
(DNA) quantification >500 IU/mL], hepatitis C virus (HCV) infection [positive for 
HCV antibody and hepatitis C ribonucleic acid (RNA) by polymerase chain reaction 
(PCR) exceeding the upper limit of normal (ULN)], positive for anti-human 
immunodeficiency virus antibody (Anti-HIV). Any of the above criteria apply; 
14. Severe chronic or active infection (including tuberculosis infection) requiring 
systemic antibacterial, antifungal, or antiviral therapy within 4 weeks prior to the 
initiation of the study treatment; 
Note: Antiviral therapy is allowed for patients with viral hepatitis. 
15. Severe cardiovascular disease, including but not limited to: 
Acute coronary syndrome or history of coronary artery intervention/stent 
implantation/coronary artery bypass grafting within the past 6 months; 
New York Heart Association (NYHA) class II-IV congestive heart failure (CHF), or 
history of NYHA class III or IV CHF. 


16. Active psychiatric disorders (schizophrenia, severe depressive disorder, bipolar 
disorder, etc.); 
17. Known allergy or intolerance to the active ingredients, excipients, or other iron 
supplements used in the investigational drug; 
18. Participation in other interventional clinical studies within 4 weeks prior to the 
initiation of the study treatment (calculated from the first day after the last 
administration of the previous study, except for interventions with non-interventional 
drugs or investigational medical devices); 
19. Other conditions in which the investigator deems the patient unsuitable for 
participation in this trial. 
 
[Study design and steps] 
This study is an open-label, multicenter, dose-escalation Phase I clinical trial. If 
you meet the inclusion criteria and agree to participate in this study, you will receive 
CNSI-Fe treatment. Based on preclinical animal study results, this study plans to start 
the dose-escalation phase with a dose of CNSI-Fe 30 mg, followed by escalating 
doses of 30 mg, 60 mg, 90 mg, and potentially adjusted to 75 mg, 120 mg, 150 mg, or 
even higher doses. Each dose group will consist of 3-6 patients who will receive 
intratumoral injection of the specified dose of CNSI-Fe on the first day. Each dose 
group will undergo dose-limiting toxicity assessment in at least 3 patients before 
proceeding to the next dose group. 
The entire study procedure includes a screening period, treatment period, and 


follow-up period. 
The screening period lasts for a maximum of 28 days. After completing 
screening examinations and assessments, eligible patients will be enrolled in the 
treatment period. During the treatment period, patients will receive up to two doses of 
CNSI-Fe (with a 21-28 day interval between doses). You will need to visit according 
to the dosing frequency and complete relevant examinations and assessments before 
and after each dose. The follow-up period is for safety follow-up and will occur 
approximately 28 days after the last dose. If you terminate or end the treatment early, 
you will need to undergo a study treatment termination visit according to the study 
protocol, which includes completing relevant examinations and assessments. Your 
study doctor will also discuss precautions and future potential treatments and 
medications with you. 
(1) Screening Period: 
Before entering the screening period, you need to read this Informed Consent 
Form (ICF). If you fully understand the content of the ICF and voluntarily agree to 
participate in this study, you need to sign the ICF. After signing the ICF, you will enter 
the screening period, during which you will undergo the following examinations and 
assessments at the hospital to help your study doctor determine if you are suitable for 
participation in this study. 
Within the first 28 days before the initial dose, the following items need to be 
completed: 
1. Sign the Informed Consent Form. 


2. Collect your basic information, including gender, age, and ethnicity/race. 
3. Measure your height and weight. 
4. The study doctor will ask and record your medical history and treatment history 
in detail, including your past medical history, medication history (within the 4 weeks 
before screening and ongoing concomitant treatment), past history of all tumors 
(including tumor staging, diagnosis date, genetic testing results), past history of all 
anti-tumor treatments, family history, surgical history, immunization history, allergy 
history, smoking history, history of drug abuse/dependence, etc. The study doctor may 
need you to provide relevant records from other hospitals, please cooperate in 
providing them. 
5. Measure your respiration, pulse/heart rate, blood pressure, and body temperature. 
6. Undergo a comprehensive physical examination. 
7. Perform a 12-lead electrocardiogram (ECG) examination. 
8. Perform a transthoracic echocardiogram examination. 
9. Collect your blood samples for glucose-6-phosphate dehydrogenase testing, iron 
examination, myocardial enzyme spectrum testing, follicle-stimulating hormone (FSH) 
testing (only for postmenopausal women over 45 years old but under 55 years old), 
viral serology testing. 
10. Collect tumor tissue samples (exploratory pharmacodynamics PD indicator 
testing, intratumoral pharmacokinetics PK study), not mandatory. 
11. Perform tumor evaluation for the brain, chest, abdomen, pelvis, and other 
suspected tumor lesions. 


12. You will be asked some questions about your physical condition. If you have any 
physical discomfort, please inform the study doctor. 
Within the first 7 days before the first dose of medication, the following tasks 
need to be completed: 
1. Assess your physical condition; 
2. Collect your blood samples for complete blood count, blood biochemistry tests, 
coagulation function tests, pregnancy tests (for women of childbearing age only), and 
tumor marker tests; 
3. Collect your urine sample for urinalysis; 
4. Ask you some questions about your physical condition. If you experience any 
discomfort, please inform the research doctor. 
After completing all these assessments and tests, if you are unable to meet all the 
inclusion criteria, you may not be able to participate in this study. You can choose 
alternative treatments, including other medications or symptomatic treatment. The 
research doctor will discuss the best treatment options with you. If you need more 
detailed information about the inclusion criteria or have any questions about the 
inclusion criteria, please feel free to ask your research doctor. 
(2) Treatment Period: 
During the treatment period, if you meet the criteria and agree to participate in 
this study, you will be assigned to a dose group (which may be 30 mg, 60 mg, 90 mg, 
75 mg, 120 mg, 150 mg, or even higher doses, depending on the progress of the study) 
in the order of enrollment. You will enter the first cycle (dose-limiting toxicity 


assessment period) and receive a specified dose of CNSI-Fe intratumoral injection on 
Day 1. Safety checks will be conducted on Day 7, Day 14, and Day 21 to evaluate 
dose-limiting toxicity. Additionally, imaging examinations will be performed in the 
third to fourth week to evaluate efficacy. If your study doctor determines that the 
benefits of continuing treatment outweigh the risks based on safety and efficacy 
assessments, you will enter the second cycle (maintenance treatment period) within 7 
days after the end of the first cycle. During the second cycle, you will receive a 
second CNSI-Fe intratumoral injection at the same dose as the initial dose, and 
clinical examinations will be conducted as in the first cycle. If your study doctor 
determines that the benefits of continuing treatment are less than the risks, you will 
not enter the second cycle and will proceed directly to the follow-up period. 
During each treatment cycle, your active cooperation in various examinations 
and treatments is required. Your study doctor will regularly conduct various clinical 
examinations according to the study protocol, including imaging examinations of the 
tumor, to evaluate the safety and efficacy of the study drug treatment. During your 
visits to the clinic, please inform the study doctor proactively about any physical 
discomfort you experience, including the duration and symptoms. The study doctor 
will also assess your physical condition through various examinations and interviews. 
The examinations you need to complete include: 
1. Measurement of body weight (performed on Day 1 of each cycle). 
2. Measurement of respiration, pulse/heart rate, blood pressure, and body 
temperature (performed on Day 1, Day 7, Day 14, and Day 21 of each cycle). 


3. Comprehensive physical examination (performed on Day 1 of each cycle and 
when deemed necessary by the study doctor). 
4. Assessment of your physical fitness (performed on Day 1 and Day 21 of each 
cycle). 
5. 12-lead electrocardiogram (ECG) examination (performed within 2 hours before 
administration on Day 1, 0.5 hours ± 5 minutes after administration, 4 hours ± 30 
minutes after administration, 8 hours ± 30 minutes after administration, 24 hours ± 30 
minutes after administration, 48 hours ± 30 minutes after administration, 72 hours ± 
30 minutes after administration, on Day 7, Day 14, and Day 21, and continuous ECG 
monitoring within 8 hours after CNSI-Fe administration; the study doctor may 
consider increasing the frequency of 12-lead ECG examinations during the trial for 
your safety). 
6. Collection of blood samples for iron examination (collected within 24 hours 
before administration on Day 1, 5 minutes ± 1 minute after administration, 15 minutes 
± 2 minutes after administration, 30 minutes ± 5 minutes after administration, 2 hours 
± 30 minutes after administration, 6 hours ± 30 minutes after administration, 10 hours 
± 30 minutes after administration, on Day 7, Day 14, and Day 21; the study doctor 
may consider increasing the frequency of testing for your safety). 
7. Collection of blood samples for complete blood count and blood biochemistry 
examination (performed on Day 7, Day 14, and Day 21; the study doctor may 
consider increasing the frequency of examinations for your safety). 
8. Collection of blood samples for coagulation function examination (performed on 


Day 7 and Day 21 of each cycle). 
9. Collection of blood samples for tumor marker detection (performed on Day 21 of 
each cycle). 
10. Collection of urine samples for urinalysis (performed on Day 7, Day 14, and Day 
21 of each cycle). 
11. Echocardiography examination (performed if necessary). 
12. Collection of blood samples for myocardial enzyme spectrum detection 
(performed if necessary). 
13. Collection of blood samples for pharmacokinetic analysis (see the section on 
biological sample collection in the study for specific blood collection time points). 
14. Collection of tumor tissue samples (exploratory PD marker detection, 
intratumoral PK study), not mandatory to provide. 
15. Inquiring about any changes in your health during the study period and informing 
the study doctor of any health conditions related or unrelated to the treatment. 
16. Inquiring about all other medications and treatments you have used during the 
study period. 
17. Tumor evaluation for suspected tumor lesions in the brain, chest, abdomen, pelvis, 
and other areas. 
(3) Followed-up period 
During the follow-up period, which occurs 28 days (±3 days) after the last dose, 
you will need to visit the research center for a check-up and evaluation. The following 
examinations and assessments will be conducted, unless you have already undergone 


them within the 3 days prior to the visit: 
1. Measurement of respiration, pulse/heart rate, blood pressure, and body 
temperature. 
2. Comprehensive physical examination. 
3. Assessment of your physical condition. 
4. 12-lead electrocardiogram (ECG) examination. 
5. Collection of blood samples for complete blood count, blood biochemistry, 
coagulation function, pregnancy test (only for women of childbearing age), tumor 
marker detection, and iron examination. 
6. Collection of urine samples for urinalysis. 
7. Inquiry about any changes in your health condition during the study period. You 
need to inform the research doctor about any health-related changes, regardless of 
whether you think they are related to the treatment you received. 
8. Inquiry about all other medications and treatments you have used during the 
study period. 
Note: 
• 
If your initial tumor imaging evaluation shows complete remission or partial 
remission, you will need to return to the research center for a repeat evaluation to 
confirm the efficacy at least 4 weeks later. 
• 
Throughout the entire trial period, you will need to complete the scheduled visits 
and related examinations as required by the protocol. 
 


[Duration of the Study] 
If you decide to participate in this study, the maximum duration of the trial will 
be approximately 4 months. 
If, after the study, the evaluation of tumor efficacy shows complete remission or 
partial remission, and your research doctor determines that continued treatment with 
the study drug would still be beneficial, you may continue to receive the study drug 
until disease progression, intolerable toxicity occurs, or the sponsor decides to 
terminate the study. 
 
[Unscheduled Visits] 
During the trial, to ensure your medication safety, the research doctor may 
require additional tests beyond the scheduled visits based on your individual 
circumstances. The results of these additional visits will be used to evaluate the safety 
of your medication. 
 
[Collection of Biological Samples during the Study] 
This study will collect your biological samples, including tumor tissue sections 
and blood samples. The provision of tumor tissue samples is not mandatory. The 
tumor tissue samples you provide will be used for efficacy evaluation and 
intratumoral pharmacokinetic (PK) studies (not mandatory). The blood samples you 
provide will be used for PK analysis. Blood samples for PK analysis will be collected 
at the following time points: 


1. CNSI-Fe first dose: PK samples will be collected within 1 hour before CNSI-Fe 
administration, and at 5 minutes ± 1 minute, 10 minutes ± 2 minutes, 15 minutes ± 2 
minutes, 30 minutes ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours 
± 15 minutes, 8 hours ± 15 minutes, 12 hours ± 30 minutes, 24 hours ± 30 minutes, 48 
hours ± 1 hour, and 72 hours ± 2 hours after administration. 
2. CNSI-Fe Second Administration (if applicable): 
The researcher may make appropriate adjustments based on the PK results of the first 
administration, such as adjusting the sampling time or increasing/decreasing the 
sampling frequency. 
PK Sampling: 
• 
Each PK sampling point requires the collection of a 3 mL blood sample for 
testing. 
• 
The collection time of PK samples may be adjusted during the study period based 
on the latest clinical data of the drug. 
Important Notes: 
1. Storage Method: 
All samples will be labeled with a label that only contains the subject number 
(anonymous code) and does not include the name. 
The identity information of the subjects corresponding to the anonymous codes 
will be kept as original data at the research institution. 
2. Destruction Time: 
All samples will be used for research purposes as described in the approved 


protocol. 
After the study or after the analysis and testing are completed, the samples will 
be destroyed according to the biological sample destruction process. 
 
[Your Rights and Obligations] 
Your participation in this study is completely voluntary. You have the right to 
withdraw from the study at any time without facing punishment, discrimination, 
retaliation, or harm to your rights, regardless of whether you provide a reason for your 
withdrawal. If you decide to withdraw for any reason, please inform your research 
doctor promptly and complete the necessary termination visits, as this will help 
evaluate the study results. 
If during the study, the research doctor obtains important information regarding 
the safety and effectiveness of the experimental medication that may affect your 
participation in this study, you have the right to be informed, and the research doctor 
will promptly notify you or your guardian. 
If you choose to participate in this study, we hope that you will commit to and 
cooperate in completing the entire research process. 
 
[Matters You Need to Cooperate With] 
If you decide to participate in this study, please pay attention to the following 
matters and comply with the corresponding requirements during the trial period: 
• 
You must visit the hospital according to the follow-up schedule agreed upon by 


the research doctor and yourself. Your timely follow-up is crucial because the research 
doctor will assess whether the treatment you are receiving is truly effective. 
• 
The research doctor will inquire about your feelings and discuss possible adverse 
events. Please inform the research doctor of any discomfort you experience during the 
trial so that appropriate measures can be taken. 
• 
The research doctor will inquire about the medications and treatments you are 
currently using. If you are taking any medications, including "prescription drugs" 
prescribed by other doctors, "over-the-counter drugs" purchased by yourself from a 
pharmacy, herbal remedies, or natural therapies, please be sure to inform your 
research doctor. 
• 
If you need to seek medical attention during the study for any discomfort, and the 
doctor who will provide the diagnosis and treatment is not your research doctor, 
please inform the doctor that you are participating in this clinical trial. 
• 
During the study period and within 6 months after the end of the study 
medication, you should strictly use contraception. If you or your sexual partner 
becomes pregnant, you must immediately inform the research doctor. 
• 
In addition to yourself, it is recommended that at least one of your family 
members be aware of the clinical trial you are participating in and be able to care 
about your condition. They should also provide feedback on your health status during 
follow-up visits. Your family members should promptly notify your research doctor if 
you experience severe discomfort (including the need for hospitalization for 
treatment). 


• 
If your address, phone number, or other contact information changes, please 
inform your research doctor promptly. 
 
[Supply of Study Medication After Discontinuation] 
After you stop using the study medication, regardless of your medical condition, 
the supply of the study medication will not continue. If your condition progresses, the 
research doctor will advise you on other suitable treatment options. 
 
[Risks of participating in the study] 
Using any medication can potentially cause discomfort, and this study is no 
exception. 
(1) Risks of using CNSI-Fe 
The medication CNSI-Fe is currently in clinical development, and complete 
safety information is still being gathered. Based on preclinical animal studies and 
clinical research data from similar drugs, potential adverse events may include: 
nausea, vomiting, diarrhea, fatigue, loss of appetite, weight loss, fever, liver function 
damage, blood disorders, tachycardia, abnormal blood sugar levels, abnormal blood 
pressure, and adverse reactions related to intratumoral injection. 
Since CNSI-Fe is administered via intratumoral injection, potential adverse 
reactions during administration may include: bleeding, infection, tumor implantation 
or metastasis, skin damage, pain, and allergic reactions to anesthesia. 
As CNSI-Fe is composed of a carbon nanoparticle suspension injection and 


ferrous sulfate for injection, according to safety data from currently marketed iron 
supplements, hypersensitivity reactions may occur when supplementing with iron. 
Additionally, since this study is an escalating dose Phase I study of CNSI-Fe, the 
appropriate dosage is still being explored, and CNSI-Fe may potentially lead to iron 
poisoning or iron overload. 
CNSI-Fe does not necessarily alleviate your condition or prolong the remission 
period of your disease. Therefore, during your participation in this clinical trial, your 
condition may remain unchanged or progress. 
During the treatment and follow-up period with the investigational drug, it is 
necessary for you to record and promptly report any adverse events you experience.               
The study doctor will assess and provide appropriate treatment measures or 
recommendations, adjust the dosing regimen if necessary, and track the prognosis and 
outcomes of all adverse events. 
(2) Other potential adverse effects or risks of participating in the study 
As part of the informed consent process, you will have a clear understanding of 
all risks associated with the study procedures. Measures will be taken to minimize the 
impact and discomfort caused by these study procedures. 
• 
Blood sampling: Blood sampling may cause some discomfort, bleeding, or 
bruising at the puncture site. Small scabs or swelling may form at the site. In rare 
cases, fainting or local infection may occur. If you feel uncomfortable during blood 
sampling, please inform the study doctor or research staff promptly. 
• 
Electrocardiogram (ECG): The placement of ECG electrodes may require 


cleaning and sometimes shaving of the area. In rare cases, local skin rash or irritation 
may occur. Otherwise, this examination is generally risk-free. 
• 
CT scan: CT scan is a type of X-ray imaging that involves low-dose radiation 
during the scanning process. You may experience claustrophobia during the scan as 
you need to remain still in a confined space. The study doctor may use contrast agents, 
which may cause pain, swelling, or mild allergic reactions such as skin rash or itching. 
In rare cases, contrast agents can cause life-threatening severe allergic reactions, such 
as anaphylactic shock. There is a slight risk of mild infection or bleeding after needle 
insertion into the blood vessel. If you know that you are allergic to contrast agents, 
please inform your study doctor and radiologist. 
• 
MRI scan: MRI scans are generally risk-free for most people. However, if you 
have certain objects or devices implanted in your body, such as a pacemaker, insulin 
pump, ear implants, joint replacements, permanent dentures, piercings, or shrapnel, 
MRI scans can be very dangerous. If you are aware of any implants or objects 
embedded in your body, you must inform the study doctor or research staff. You may 
experience claustrophobia during the scan as you need to remain still in a confined 
space. 
• 
If you are pregnant or planning to become pregnant, you cannot participate in this 
study. The effects of the study drug on unborn fetuses and breastfeeding infants are 
not yet clear, and the impact on sperm or semen is unknown. You or your partner must 
use contraception for at least 6 months after the last dose of the study drug. If you or 
your partner becomes pregnant during the study or within 6 months after the last dose 


of the study drug, you should inform the study doctor. The study doctor will then 
follow up on the pregnancy. During the follow-up period, you will need to provide 
information about the pregnancy. 
During the use of CNSI-Fe or other study procedures, adverse reactions as 
mentioned above may occur, although they may vary from person to person. You may 
not experience any adverse reactions or may experience only some of them. 
In addition to the risks mentioned above, any medication and procedure may also 
involve unforeseen risks. If you experience any discomfort, new changes in your 
condition, or any unexpected situations, whether related to the study drug or not, you 
should promptly notify the study doctor. The study doctor will assess and provide 
medical treatment accordingly. 
You will need to attend regular follow-up visits at the hospital during the study, 
undergo the specified examinations and evaluations as outlined in the study protocol. 
This will take up your time and may cause inconvenience or trouble. 
 
[Pregnancy and Contraception] 
CNSI-Fe has not been extensively studied with controlled clinical trials in 
pregnant women. Therefore, it is important to have a thorough discussion with your 
study doctor about all family planning options and/or alternative plans before 
participating in this study. 
The use of CNSI-Fe during pregnancy may cause harm to the fetus. Therefore, it 
is recommended that both women and male participants with reproductive potential 


take effective contraceptive measures throughout the entire study period and for at 
least 6 months after the study ends. Women should not breastfeed during their 
participation in this study. 
If you are a woman of childbearing age, you must avoid becoming pregnant 
during the entire study to prevent adverse effects on fetal development and health. 
Before participating in the trial, you will undergo a pregnancy test to ensure that 
pregnant women cannot participate. If you suspect that you are pregnant during the 
study, please contact your doctor immediately for further guidance. 
If you are a male patient, you must agree to take adequate and effective 
contraceptive measures or practice abstinence, and have no plans to impregnate a 
female partner from the date of signing this informed consent form until 6 months 
after the last dose of the study drug, and avoid sperm donation. 
 
[Potential Benefits of Participation] 
By participating in this clinical study, there is a possibility that your condition 
may improve. However, it is also possible that the expected effects may not be 
achieved, or disease progression may occur. The collection of tumor tissue 
samples/blood and other tests may not directly benefit you, but your study doctor will 
closely monitor your disease status during the study. Your participation will also 
contribute to further research and understanding of such diseases, ultimately 
improving the diagnosis and treatment of these conditions. We appreciate your 
participation in scientific research and contribution to the advancement of medicine. 


 
[Other Treatment Options Available to You] 
Your doctor will inform you about other treatment options currently available to 
you. You can discuss these alternative treatments with your doctor to decide whether 
to participate in this study. 
If you decide not to participate in this study, your doctor will still advise you on 
other suitable treatment options. 
 
[Prohibited Concomitant Medications and Treatments] 
During the study treatment period, you need to avoid using the following 
medications or treatments: 
• 
Other anti-tumor treatments (including but not limited to chemotherapy, radiation 
therapy, immunotherapy, targeted therapy, approved anti-tumor Chinese medicine, 
surgery, etc.), including experimental treatments or approved anti-tumor treatments. 
• 
Other concomitant medications/treatments that may affect the evaluation of the 
primary endpoints, as determined by the study doctor. 
 
[Regarding Fees] 
The sponsor provides the investigational drug (CNSI-Fe) free of charge. The 
sponsor will cover all examination costs related to the trial during the study period. 
However, the costs for examinations and treatments related to other concurrent 
diseases and the best supportive care for your condition will not be reimbursed. 


As a participant, you will not receive any compensation for participating in this 
study. However, you will receive some reasonable allowances, as follows: 
• 
A transportation allowance of 200 yuan will be provided for each visit to the 
study center. 
• 
A nutrition allowance of 200 yuan will be provided for each PK blood sample 
collection, as PK analysis requires your blood samples. The PK study for the first 
administration of CNSI-Fe will involve 13 PK blood collections, totaling a nutrition 
allowance of 2600 yuan. The PK study for the second administration of CNSI-Fe (if 
applicable) will provide a corresponding nutrition allowance based on the actual 
number of blood collections (200 yuan per collection). 
• 
A work absence allowance of 1000 yuan will be provided for PK blood 
collections that need to be conducted at the hospital. 
• 
A subsidy of 500 yuan will be provided for each tissue sample collection for 
efficacy evaluation and intratumoral PK study. The study anticipates a maximum of 2 
tissue collections, thus providing a maximum subsidy of 1000 yuan (final subsidy will 
be based on the actual number of collections). 
All the above allowances will be settled based on the actual number of visits. 
 
[Handling of Damages] 
If you experience any adverse events related to the trial during the study period, 
please inform your investigator promptly. The investigator will provide you with 
timely and scientific free treatment (the medical expenses will be borne by Sichuan 


Enray Pharmaceutical Technology Company.). In the case of severe adverse events 
related to the trial, besides providing free treatment, Sichuan Enray Pharmaceutical 
Technology Company. will provide appropriate financial compensation. All expenses 
will be paid by Sichuan Enray Pharmaceutical Technology Company. The company 
has purchased clinical trial liability insurance for this study, and you will receive 
corresponding compensation from the insurance company according to the insurance 
contract. If there are any remaining expenses that are not covered by the insurance 
company, Sichuan Enray Pharmaceutical Technology Company. will be responsible 
for compensating them, and the sponsor will handle the claims. Medical accidents 
caused by improper operation by medical staff during the trial will be borne by the 
hospital. 
 
[Privacy and Confidentiality Principles] 
Your privacy is of utmost importance to us, and we will keep your personal and 
medical information confidential. 
The researchers at this hospital, the ethics review committee, drug regulatory 
authorities, other regulatory agencies, as well as the sponsor or its representatives, 
may review your data to ensure the accuracy of the information and compliance with 
legal requirements. Your research information will be identified with a specific 
research code, and the specific code information will be securely stored at the hospital. 
The information received and processed by the sponsor does not include your name or 
any personal information that could identify you. Any identifying information about 


you will not be disclosed when publishing the research information and data obtained 
from this study in scientific conferences or journals. 
 
[Conflict of Interest] 
The funding for this clinical trial is provided solely by Sichuan Enray 
Pharmaceutical Technology Company. The researchers participating in this trial have 
no financial or non-financial interests that conflict with their responsibilities to the 
sponsor. 
 
[Voluntary Participation in the Study] 
This clinical study will adhere to the "Good Clinical Practice for Drugs" and the 
"Helsinki Declaration," and has obtained approval from the Clinical Trial Ethics 
Committee of our institution to ensure that your rights are not violated during this 
trial. 
Whether or not to participate in the study is entirely up to you. You have the right 
to refuse to participate in this study or to stop using the medication or withdraw from 
the study at any time without affecting your relationship with your doctor or causing 
any loss of medical or other benefits. If you choose to withdraw from the clinical 
study, your research doctor will consider your safety and ask about your use of the 
investigational drug, and may recommend that you undergo certain medical 
examinations upon withdrawal. Additionally, if you fail to comply with the relevant 
trial requirements during the clinical study or if your research doctor deems you 


unsuitable to continue participating in the trial, in order to protect your interests, the 
research doctor has the right to terminate your participation in the study. 
 
[Other Information] 
During the study, if the research doctor becomes aware of any important 
information related to the research drug that is beyond the scope of this informed 
consent form and may affect your suitability to continue participating in the study, the 
researcher will promptly notify you. If necessary, you will also need to sign a written 
informed consent form regarding this matter. 
 
[Contact Information] 
If you would like to learn more about this study, please contact your researcher. 
If you experience any discomfort during the study, you should also inform the 
researcher. The principal investigator of this study is Professor Yongsheng Wang. This 
research protocol has been approved by the Clinical Trial Ethics Committee of West 
China Hospital, Sichuan University. If you have any questions related to your own 
rights and interests, please contact the National Drug Clinical Trial Institution/GCP 
Center of our institution at 028-85422707; Clinical Trial Ethics Committee at 
028-85423237. 
In the above content, we have introduced to you the purpose, methods, potential 
therapeutic benefits, and possible adverse reactions of this study. If you are willing to 
participate in this study and can comply with the requirements of the trial protocol and 


fully cooperate with the researchers, please sign this informed consent form. 
This informed consent form is in duplicate, with one copy for you and one 
for the researcher. Please keep this document properly. 
Acknowledgment: The development and progress of medical science are 
inseparable from clinical trials. Your participation will contribute to the advancement 
of medical science. We will always remember your dedication and express our sincere 
gratitude to you! 
 


Informed Consent Form Signature Page 
I have carefully read the information about this study and had the opportunity to 
discuss it with the doctor and ask questions. All my questions have been answered in a 
clear and understandable manner. After fully understanding the content of the 
informed consent form and considering the benefits and risks of participating in this 
study, I voluntarily agree to participate. I understand the following: 
1. As a participant, I will comply with the requirements of the informed consent form 
and voluntarily participate in this study. My decision is not influenced by any 
individual or organization, and I have the right to withdraw from the study at any time 
without discrimination or retaliation. My medical treatment and rights will not be 
affected by my decision. 
2. The results of this clinical study will only be used for research purposes. Personal 
information collected during the study will be kept confidential and protected 
according to legal regulations. The use of research results will be limited to authorized 
government purposes. 
3. If I decide to withdraw from the study, especially due to the use of study 
medication, I will inform the researcher about my health condition and complete the 
necessary exit visit examinations. This will be beneficial for both myself and the 
entire study. 
4. In the event of any adverse events related to the study medication, I will receive 
appropriate and free treatment from the researcher and the sponsor. The sponsor 
and/or insurance company will be responsible for any related expenses. 


5. I will receive a signed copy of the informed consent form. 
Participant's Name (Please print): 
Participant's Signature: 
Contact Phone Number: 
Date and Time of Signature: 
(If the participant lacks the ability to sign or understand, add or replace the 
following section) 
Guardian's Name (Please print): 
Guardian's Signature: 
Relationship to Participant: 
Contact Phone Number: 
Date and Time of Signature: 
 
Witness's Name* (Please print) (if applicable): 
Witness's Signature: 
Contact Phone Number: 
Date and Time of Signature: 
*The witness is an impartial individual who is not involved in the clinical trial and is 
not influenced by any clinical trial personnel. When the participant or their guardian 
lacks the ability to read, the witness reads the informed consent form and other 
written materials and witnesses the consent process. 
Researcher's Declaration: 


I confirm that I have explained the details of this trial to the participant, 
including their rights and the potential risks and benefits, and have provided 
satisfactory answers to any questions raised by the participant. The participant has 
expressed understanding and satisfaction. 
Researcher's Name (Please print): 
Researcher's Signature: 
Contact Phone Number: 
Date and Time of Signature: