Carbon Nanoparticle-Loaded Iron [CNSI-Fe(II)] Dose Escalation Study for the Treatment of Advanced Solid Tumors: Phase 1 Clinical Trial
Phase: PHASE1
Conditions: Advanced Solid Tumor, Lung Cancer, Pancreas Cancer, Breast Cancer, Thyroid Cancer, Colorectal Cancer, Cervical Cancer, Ovarian Cancer, Vulva Cancer
Sponsor: Sichuan Enray Pharmaceutical Sciences Company

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