A Study of Liposomal Irinotecan in Combination With Temozolomide and Bevacizumab in Patients With Relapsed or Refractory Soft Tissue Sarcoma
Phase: PHASE2
Conditions: Soft Tissue Sarcoma (Excluding GIST)
Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Version 1.1, April 25,2025
Clinical Study of Irinotecan Liposome Comb-
ined With Temozolomide and Bevacizumab in
the Treatment of Relapsed Refractory Soft
Tissue Sarcoma
Scheme
Version: 1.1
Date of version: 25 April 2025
Professor Ying Dong, Principal Investigator of the Clinical
Study
Lead Clinical Trial Institution: The Second Affiliated Hospital of
Zhejiang University School of Medicine
Sponsoring Institution: The Second Affiliated Hospital of Zhejiang
University School of Medicine

Version 1.1, April 25,2025
Page 1
Scenario Summary
Research topic
Clinical study of irinotecan liposome combined with temozolomide
and bevacizumab in the treatment of relapsed refractory soft tissue
sarcoma
Version nu-
mber
V1.1
Version date
April 25,2025
Principal Inv-
estigator
Dong Ying
Nature of the
study
Prospective, single-arm, phase II study
Purpose of
research
Primary research objectives:

To evaluate the efficacy and safety of liposomal irinotecan
combined with temozolomide and bevacizumab in the treatment of
relapsed or refractory soft tissue sarcoma by assessing progression-
free survival (PFS) and safety.
Secondary research objectives:

To evaluate the objective response rate (ORR), 12-
week progression-free survival (PFS), overall survival (OS),
disease control rate (DCR), and duration of response (DoR) of
liposomal irinotecan combined with temozolomide and bevaci-
zumab in the treatment of relapsed/refractory soft tissue sarcoma.

To explore the molecular predictive markers associated
with the efficacy of irinotecan combined with temozolomide and
bevacizumab in the treatment of relapsed/refractory soft tissue
sarcoma.
Study end po-
int
Primary research end point:

progression @-@ free survival (PFS)

Safety end points: Adverse events (AE)/serious adverse
events (SAE) (judged according to NCI-CTCAE 5.0).
Secondary end points

objective response rate (ORR)

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Page 2

12-week PFS rate;

overall survival (OS);

Disease Control Rate (DCR);

Duration of relief (DoR);

Exploratory end points: efficacy-related molecular predictive markers, etc.
Subject
investiga-
ted
Patients with metastatic or unresectable recurrent refractory soft tissue
sarcoma confirmed by histological evidence
Research
design
This study is a prospective, single-arm, phase II design aimed at
evaluating the efficacy and safety of liposomal irinotecan combined with
temozolomide and bevacizumab in the treatment of relapsed or refractory
soft tissue sarcoma.
The study investigates patients with metastatic or unresectable
recurrent refractory soft tissue sarcoma confirmed by histological
evidence. After signing informed consent and passing screening, subjects
receive treatment. The primary endpoints are progression-free survival
(PFS) and safety.
Irinotecan liposome (II) + temozolomide + bevacizumab, with a 21-
day cycle, until disease progression or intolerable toxicity.
Safety visits: After enrollment, subjects will undergo safety visits on
Day 1 of each treatment cycle and at the end of treatment. Subjects will
receive survival follow-up every 3 months after treatment completion.
Imaging assessment: All lesions were recorded and evaluated
according to RECIST v1.1. Unless otherwise specified, the allowable
window for imaging examinations was ±7 days. During the study period,
unplanned imaging examinations could be performed when tumor
recurrence or metastasis was suspected.
Screening period: Imaging examinations of the chest, abdomen, and
pelvis are required. Enhanced MRI/CT scans (with a slice thickness ≤5
mm) are needed for the abdomen and pelvis, while chest CT scans (with
a slice thickness ≤5 mm) are required for the chest. For suspected brain
metastases, enhanced MRI/CT of the cranium is also required to exclude
brain metastases. Bone scans are necessary to confirm or clinically
suspect bone metastases. Baseline tumor assessment should be completed
within 2 weeks before randomization. If the investigator determines that

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the imaging findings represent the subject's baseline status, baseline
imaging examinations...

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It can be extended to the first 4 weeks before randomization;
Tumor recurrence follow-up: Imaging examinations were performed every 12 weeks
after treatment initiation, including contrast-enhanced MRI/CT scans. Additional
imaging of the suspected metastatic site was required if metastasis was suspected. The
imaging evaluation continued until imaging progression or recurrence, initiation of
alternative antitumor therapy, withdrawal of informed consent, loss to follow-up, or
death.
Research on
drug
2
Iritinib Liposome (II) 56.5 mg/m D 1
2
Temozolomide 100 mg/m /day × 5 days
Bevacizumab 7.5 mg/kg iv D1
Administrat-
ion method

2
Iliotinib liposome: 56.5 mg/m
, intravenous infusion for 90
minutes (+30 minutes), with 1 study cycle defined as days 1 and
3.

2
temozolomide: 100 mg/m /day for 5 days, with 3 weeks as one
study cycle;

bevacizumab: 7.5 mg / kg, intravenous infusion, D 1,3 week as
one study period.
Enrollment
Criteria
Participants must meet all the following inclusion criteria to be
eligible for this study.
1.
Age ≥14 years, gender not restricted;
2.
For metastatic or unresectable recurrent refractory soft tissue
sarcoma confirmed by histological evidence, the combination
therapy regimen may be considered based on the investigator's
assessment.
3.
Disease progression or intolerable toxicity after at least one line
of systemic therapy (with or without targeted therapy).
4.
at least one measurable lesion (RECIST v1.1);
5.
ECOG：0～2；
6.
expected survival ≥3 months;
7.
The primary organ functions are adequate, meaning the following
criteria are met (no blood components or cell growth factors were
administered within 14 days prior to randomization):
（1）
9
9
Neutrophils ≥1.5×10 /L; platelets ≥80×10 /L; hemoglobin
≥9g/dl; serum albumin ≥3g/dl;
（2）Total bilirubin ≤1.5 times the upper limit of normal

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(biliary obstruction allows biliary drainage); ALT and AST ≤3
times the upper limit of normal (for patients with liver metastases,
the limit may be relaxed to ≤5 times the upper limit of normal).

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（3）Serum creatinine ≤1.5 times the upper limit of normal, and creatinine clearance ≥
60 ml/min;
（4）INR ≤1.5 times the upper limit of normal and APTT ≤1.5 times the upper limit
of normal (eligible for screening if stable-dose anticoagulation therapy such as low
molecular weight heparin or warfarin is being used and the INR is within the expected
therapeutic range of the anticoagulant);
（5）ECG: QTcF ≤450ms (male), ≤470ms (female);
（6）Cardiac ultrasound: LVEF (left ventricular ejection fraction) ≥
50%;
8.
Women of childbearing age must have a negative blood pregnancy test within 3
days prior to randomization and be willing to use appropriate contraceptive methods
during the trial and for 6 months after treatment. For men, consent must be obtained to
use appropriate contraceptive methods during the study and for 3 months after
treatment.
9.
All participants voluntarily enrolled in this study and signed the informed consent
form.
Exclusion Criteria Subjects who meet any of the following criteria will not be
eligible for this study:
1.
patients with known central nervous system metastases;
2.
severe gastrointestinal dysfunction (with bleeding, obstruction; inflammation
greater than grade 2; diarrhea greater than grade 1);
3.
patients with a prior history of treatment with irinotecan, temozolomide,
bevacizumab, or similar agents;
4.
Presence of third space effusion (e.g., massive pleural effusion) that cannot
achieve a stable state (no intervention required after drainage tube removal) within the
first two weeks prior to randomization, excluding ascites.
5.
Patients with clinical symptoms of ascites requiring puncture and drainage, or
those who have undergone ascites drainage within the past 3 months (excluding cases
where imaging only shows minimal ascites that is controllable but without clinical
symptoms);
6.
Currently diagnosed with interstitial pneumonia or interstitial lung disease, or with
a history of interstitial pneumonia or interstitial lung disease requiring corticosteroid
therapy, or other conditions that may interfere with the assessment and management of
immune-related pulmonary toxicity, such as pulmonary fibrosis, organizing pneumonia
(e.g., obstructive bronchiolitis), pneumoconiosis, drug-induced pneumonia, idiopathic
pneumonia, or subjects with active pneumonia or severe impaired lung function on
chest CT during the screening period; active tuberculosis;

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7.
active autoimmune disease or a history of autoimmune disease with potential for
recurrence

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Inclusion criteria include but are not limited to autoimmune
hepatitis, interstitial pneumonia, uveitis, enteritis, pituitaryitis,
vasculitis, nephritis, hyperthyroidism, and hypothyroidism (par-
ticipants whose conditions can be controlled solely through
hormone replacement therapy may be enrolled); those with non-
systemic dermatoses such as vitiligo, psoriasis, or alopecia, well-
controlled type 1 diabetes mellitus treated with insulin, or
childhood asthma that has been completely remitted without
subsequent intervention in adulthood may also be enrolled.
8.
known peripheral neuropathy (CTCAE grade ≥3);
9.
known dihydropyrimidine dehydrogenase (low activity) or
deficiency;
10. Serious infection (CTCAE> grade 2) occurring within the first 4
weeks of randomization, such as severe pneumonia, bacteremia,
or infection-related complications requiring hospitalization;
presence of symptoms and signs of infection within the first 2
weeks of randomization necessitating intravenous antibiotic
therapy (excluding prophylactic antibiotic use).
11. received any of the following treatments:

Concomitant medications within the first 2 weeks of
randomization contained strong inhibitors/strong inducers
of CYP3A4 or CYP2C8, or strong inhibitors of UGT1A1.

Administration of immunosuppressants or systemic cortic-
osteroids for immunosuppression during the first 2 weeks
(dose>10
mg/day
of
prednisone
or
other
equivalent
therapeutic corticosteroids);

received
radiotherapy
within
the
first
2
weeks
of
randomization;

Surgery (e.g. thoracotomy, laparotomy) in the first 4 weeks
of randomization;

Received any other investigational drug in the previous 4
weeks, except for observational (non-interventional) clini-
cal studies or follow-up in intervention studies.
12. Impaired coagulation function, bleeding tendency, or ongoing
thrombolytic or anticoagulant therapy. Prophylactic use of low-

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dose aspirin (≤100 mg/day) and low-molecular-weight heparin
(enoxaparin 40 mg/day or other low-molecular-weight heparins
at equivalent doses) is permitted;
13. Patients with poorly controlled cardiac clinical symptoms or
diseases, such as: (1) NYHA class 2 or higher heart failure; (2)
unstable angina; (3) myocardial infarction (MI) within the past 6
months; (4) clinically significant supraventricular or ventricular
arrhythmias requiring treatment or intervention.

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14. Malignant tumors other than recurrent or refractory soft tissue sarcoma occurring
within the preceding 3 years, excluding well-treated carcinoma in situ, basal cell
carcinoma of the skin, or squamous cell carcinoma, etc.
15. Known hypersensitivity to irinotecan liposomes, other liposomal products,
temozolomide, bevacizumab, or any component of the aforementioned products;
16. known to have acquired immunodeficiency syndrome (AIDS) or HIV testing
positive, active syphilis infection;
17. A clear history of neurological or psychiatric disorders, including epilepsy or
dementia;
18. According to the investigator's assessment, the subject may have other factors that
could lead to forced discontinuation of the study, such as non-compliance with the
protocol, having other serious illnesses (including psychiatric disorders) requiring
concomitant treatment, clinically significant laboratory test values with severe
abnormalities, or family/social factors that may affect the subject's safety or the
collection of trial data.
Criteria for
discontinuat-
ion of study
therapy
Discontinuation of study therapy does not mean withdrawal from the
study.
1.
The subject requested to discontinue the trial drug therapy;
2.
pregnancy occurred during the study;
3.
The occurrence of any clinical adverse event, abnormal laborat-
ory findings, or other medical conditions that may render
continued medication unbeneficial to the subject;
4.
The overall deterioration of health status makes it impossible to
continue participating in the trial.
5.
loss to follow-up;
6.
Subject death;
7.
Other reasons for discontinuation of treatment were considered
by the investigators.
Exit study cri-
teria
Reasons for subject withdrawal from the study may include:
1.
The subject withdrew informed consent and declined further
follow-up;
2.
loss to follow-up;
3.
Subject death;
4.
the sponsor discontinued the study.

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Study termin-
ation criteria
The study termination criteria include but are not limited to:
1.
identifying an unexpected, significant or unacceptable risk to the
patient;
2.
During the execution of the trial, significant errors were identified
in the protocol.
3.
The study drug/trial treatment is ineffective, or continuing the
trial is meaningless;
4.
The sponsor decided to terminate the study due to reasons such
as significant delays in patient enrollment or frequent protocol
deviations.
Sample capac-
ity
The progression-free survival (PFS, Recist v1.1) of irinotecan
liposome (II) combined with temozolomide and bevacizumab in the
treatment of relapsed/refractory soft tissue sarcoma was expected to
increase from the previous study result of 3.8 months to 7.5 months.
With an alpha=0.05 and power=0.80, a sample size of 21 cases was
required, considering a 10% loss to follow-up, with a planned
enrollment of 24 cases.
This study aims to preliminarily evaluate the progression-free
survival (PFS, Recist v1.1) of irinotecan liposome (II) combined
with temozolomide and bevacizumab in the treatment of relapsed/
refractory soft tissue sarcoma.
Statistical
method
General analysis
For continuous data, the statistical measures of frequency, mean,
standard deviation, median, minimum, and maximum were used for
summarization; for categorical data, the statistical measures of
frequency and percentage were employed for summarization; for
time-event data, the Kaplan-Meier method was utilized to estimate the
survival function and the median time to event, and survival curves
were plotted.
Efficiency analysis
The analysis of the primary end points will be based on the per @-@
protocol set.
For the primary endpoint of PFS, the median was estimated using the
Kaplan-Meier method, with the 95% confidence interval calculated by
the Brookmeyer-Crowley method, and survival curves were plotted.
The analysis of primary endpoint safety will be conducted in the SS

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(Safety Analysis Set) population. The safety endpoint analysis will be
performed in the overall population.
For TEAEs and SAEs, the percentage of occurrences (defined as the
proportion of patients who experienced at least one event) and the
incidence rate (number of risk events per 100 patient-years) will be
reported. The 95% confidence interval for the percentage of occurre-
nces will be calculated using the exact method of the binomial
distribution.

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Time.
For the secondary efficacy endpoints, including objective response rate (ORR), 12-
week progression-free survival (PFS), overall survival (OS), disease control rate
(DCR), and duration of response (DoR), the number and percentage of subjects with
events and censored data were collected, and summary statistics were provided for
event types and causes of censored data. The median values were estimated using the
Kaplan-Meier method, and the 95% confidence intervals for median ORR/PFS/OS/
DCR/DoR were estimated using the Brookmeyer-Crowley method, with survival
curves plotted.
Study timeline Estimated first participant enrollment time after ethics approval
The estimated time of enrollment for the last subject is 1 year after initiation.
Estimated 2 years after the study ends

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Clinical Trial Flowchart
All tests/inspections are recommended items, and specific tests/inspections are
subject to clinical practice 1.Screening steps
Project
Filter period
[1]
Baseline , -14 days
Explanatory note
Enrollment assessment
Sign the informed consent
form
√
[2]
Informed consent for enrollment in this study must be obtained during the screening phase. The
designated screening procedures for this study shall not commence until written informed consent is
secured. Special provisions apply to baseline tumor imaging examinations, with specific details to be
consulted in the "Tumor Imaging Assessment" section of this flowchart during the screening
period. Participants who fail pre-treatment screening are permitted one additional screening
opportunity . For this re-screening phase, participants must obtain renewed informed consent and
complete re-registration to receive a new participant number.
Verify admission criteria
√
Assessment during the screening period (including re-enrollment screening)
Demographic data
√
Medical history
√
Including medical history and tumor history (initial diagnosis, treatment course, etc.).
Safety evaluation
ECOG score
√
Administer within 14 days before the first dose
Check-up
√
Administer within 14 days before the first dose
Vital sign
√
Including blood pressure, pulse, body temperature, and respiratory rate. Screening visits are
performed during and within 72h before the first dose. If screening is completed within 72h before
the first dose, no further testing is required before the first dose.
Collect and consolidate
medication/treatment
√
Including information on combination therapy within 1 month prior to signing the informed
consent form
Collect adverse events
√
Including symptoms and signs

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Page 10
Project
Filter period
[1]
Baseline , -14 days
Explanatory note
12 lead ECG
√
Administer within 14 days before the first dose
Echocardiogram
√
Including LVEF assessment, performed within 14 days prior to the first dose
Routine blood test
√
Include complete blood count and differential (white blood cells, red blood cells, lymphocytes,
neutrophils, hemoglobin, etc.), and platelet count. Test within 14 days before the first dose. If the
screening period is completed within 72h before the first dose, no additional testing is required
before the first dose.
Routine urine test
√
The tests include white blood cells, red blood cells, urine protein, urine occult blood, and urine
glucose. These tests should be performed within 14 days before the first medication. If urine protein
levels are ≥2+ during the screening phase, a 24-hour urine protein quantification test must be
added. If the screening phase is completed within 72 hours before the first medication, no additional
testing is required prior to the initial administration.
Fecal occult blood
√
Test within 14 days before first medication.
Blood biochemistry
√
Including liver function (ALT,AST, total bilirubin, conjugated bilirubin,AKP,γ GT), kidney
function (BUN or serum urea level, creatinine, uric acid), total protein, albumin, fasting blood
glucose, triglycerides, cholesterol, amylase (if abnormal and clinically significant, lipase must be
measured), blood glucose,LDH. Testing should be performed within 14 days before the first dose. If
screening tests are completed within 72 hours before the first dose, no additional testing is required
before the first dose.
Blood electrolytes
√
Including potassium, sodium, calcium, chloride, magnesium, and phosphorus ions. Test within 14
days before the first dose. If the screening period is completed within 72h before the first dose, no
further testing is required before the first dose.
Coagulation function
√
International Normalized Ratio (INR), if INR is not available, prothrombin time (PT) is used
instead. Test within 14 days before the first dose.
Myocardial enzyme profile
and troponin
√
The myocardial enzyme spectrum includes creatine kinase (CK), creatine kinase isoenzyme (CK-
MB), lactate dehydrogenase (LDH); and troponin (CTn1) detection.Test within 14 days before first
medication.
Tumor markers
√
Test within 14 days before first medication.
Thyroid function
√
Including TSH, FT3, and FT4.

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Page 10
Pituitary-adrenal axis fu-
nction
√
This includes the measurement of 8 point ACTH and cortisol, as well as the measurement of follicle-
stimulating hormone, which is performed during the screening period and only later if there are
any suspicious symptoms.

Version 1.1, April 25,2025
Page 11
Project
Filter period
[1]
Baseline , -14 days
Explanatory note
Virological testing
√
Including HIV-Ab,HBV, and HCV infection testing. For HBV testing: During the screening phase, test
HBsAg to determine if HBV infection is present. If positive, test HBsAg(quantitative),HBsAb(qualitati-
ve),HBcAb(qualitative),HBeAg(qualitative),HBeAb(qualitative), and HBV-DNA(qualitative; if positive,
also test quantitative). For HCV testing: During the screening phase, test HCV-Ab to determine if HCV
infection is present. If positive, test HCV-RNA(qualitative; if positive, also test quantitative).
Blood HCG test
√
For women of childbearing age only (WOCBP). Testing must be performed within 72h before the
first dose.
Effectiveness evaluation
Tumor Imaging Assessm-
ent
√
Baseline imaging assessment must be performed according to the RECIST1.1 criteria, including
enhanced CT scans of the chest, abdomen, pelvis, and affected areas. If there is an allergy to
enhanced CT contrast agents, a chest CT plain scan plus abdominal and pelvic MRI scans may be
performed. Bone scans are only performed when clinically indicated. If routine tumor imaging
assessment has been completed before the informed consent form is signed, as long as these CT or
MRI scans were completed within 28 days before the initiation of the study drug (bone scans may be
completed within 42 days before the first dose), there is no need to repeat CT or MRI during the
screening period. Brain MRI or enhanced CT scans are performed during the screening period.
Other
Biomarker collection
√
If applicable, including blood sample collection and tumor histopathology section collection.

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Page 12
2.
Treatment Phase Steps
Treatment period [3]
(21 days as a cycle)
Project
Treat
Maintenance
treatment
Explanatory
note
Safety evaluation
ECOG score
√
√
Perform within 72 hours before
each administration
Check-up
√
√
A physical examination of the target site should be performed within 72h before each dose, including at least the
heart, lungs, abdomen, and skin.
Vital sign
√
√
Including blood pressure, pulse, body temperature, and respiratory rate. Conducted within 72
hours before each medication administration.
Collect
and
consolidate
medication/treatment
√
√
Collect adverse ev-
ents
√
√
Including symptoms and
signs
12
[4
lead ECG
]
√
Starting from the 2 cycle, each cycle is D 1 detected.
Echocardiogram
During the study period, examinations were conducted according
to local standards when clinically indicated.
Including complete blood count and differential (leukocytes, red blood cells, lymphocytes, neutrophils,
hemoglobin, etc.) and platelet count. Testing should be performed within 72 hours before each medication
administration.
Routine
blood test
√
√
Including white blood cells, red blood cells, urinary protein, urinary occult blood, urine.
Sugar 2 hours before each
Test within 7 days of medication.
Urine protein ≥
If 2+
，Xu

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Page 13
Quantitative determination of 24h urine protein in Gacha.
Routine urine test
√
√
Fecal occult blood
√
√
Test within 14 days before first medication.
Including liver function (ALT,AST, total bilirubin, conjugated bilirubin,AKP,γ-GT), renal
function (BUN or serum urea level, creatinine, uric acid), total protein, albumin, fasting blood
glucose, triglycerides, cholesterol, amylase (if abnormal and clinically significant, lipase should
be measured additionally), blood glucose,LDH. Testing should be performed within 72 hours
before each medication administration.
Blood biochemistry
√
√
Blood electrolytes
√
√
Including potassium, sodium, calcium, chloride, magnesium, and phosphorus ions. Testing
should be performed within 72 hours before each medication administration.
Coagulation function[4]
√
International Normalized Ratio (INR), if INR is not available, prothrombin time (PT) is used
instead. From cycle 2, every cycle D 1 is tested.
√
[4
Myocardial enzyme spectrum
and troponin
]
√
√
Starting from the 2 cycle, each cycle is D 1 detected.
Effectiveness evaluation
Tumor imaging assessment must be performed according to the RECIST1.1 criteria.

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Page 13
Assessments should be performed every 2 cycles after the initiation of treatment, regardless of
whether the drug is

Version 1.1, April 25,2025
Page 14
√
No delay. For subjects who have started treatment, i.e., more than 12 months after the first
study dose, if continued tumor assessment is still required, it should be performed every 12
weeks (±7 days). If a new lesion is suspected, it should be examined as appropriate. The first
PR/CR must be confirmed after 4~6 weeks; the first PD must be confirmed after 4~6 weeks
(except for significant changes in symptoms or rapid tumor progression). Enhanced CT scans
should be performed for the chest, abdomen, pelvis, and sites of lesions. If there is an allergy to
enhanced CT contrast agents, chest CT plain scans plus abdominal and pelvic MRI scans may
be performed. Bone scans should only be performed when clinically indicated. If disease
progression (e.g., symptom worsening) is suspected, unplanned imaging studies may be
performed.
Tumor Imaging Assessment
√
Research and treatment
Iritinib Liposome (II)
√
√
Temozolomide
√
√
Bevacizumab
√
√

Version 1.1, April 25,2025
Page 15
3.
Treatment Completion and Follow-up Phase Steps
Project
[5
Treatment ended
]
Follow-up period
Explanatory note
[6
Safety
follow
@-@
up
]
[7
Survival
follow-up
]
Safety evaluation
ECOG score
√
√
Check-up
√
√
Vital sign
√
√
Including blood pressure, heart rate, body temperature, and respiratory
rate.
Collect and consolidate
medication/treatment
√
√
Collect adverse events
√
√
Including symptoms and signs
12 lead ECG
√
Echocardiography
√
During the study period, examinations were conducted according to
local standards when clinically indicated.
Routine blood test
√
√
The complete blood count (CBC) and platelet count were performed.
Routine urine test
√
√
If the proteinuria is ≥2+, the 24h urine protein quantification must be
added.
Blood biochemistry
√
√
Including liver function (ALT,AST, total bilirubin, conjugated bilirubin,
AKP,γ-GT), renal function (BUN or serum urea level, creatinine, uric
acid), total protein, albumin, fasting blood glucose, triglycerides,
cholesterol, amylase (if abnormal and clinically significant, lipase should
be measured), blood glucose,LDH.
Blood electrolytes
√
√
Including potassium, sodium, calcium, chloride, magnesium, and pho-
sphorus ions.

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Page 15
Coagulation function
√
International standardization ratio (INR), if INR is not available,
prothrombin time (PT) is used instead.
Myocardial enzyme profile
and troponin
√

Version 1.1, April 25,2025
Page 16
Project
[5
Treatment
ended
]
Follow-up period
Explanatory note
[6
Safety
follow @-@ up
]
[7
Survival
follow-up
]
Tumor markers
√
Thyroid function
√
Test TSH, FT4, FT3.
Virological test-
ing
√
HBV infected persons are tested for HBV-DNA; HCV infected persons are tested
for HCV-RNA.
Blood HCG test
√
For women of childbearing age only (WOCBP).
Effectiveness evaluation
Tumor Imaging
Assessment
√
√
√
For subjects who discontinued trial treatment for reasons other than imaging-
confirmed disease progression, imaging evaluation must be performed at the end
of treatment if no imaging was conducted within 4 weeks prior to trial
termination. Additionally, tumor response should be assessed every 3 months
post-trial until documented disease progression or initiation of new oncology
therapy. This includes contrast-enhanced CT scans of the chest, abdomen, pelvis,
and affected areas. For patients with contrast CT agent allergies, chest CT plain
scans combined with abdominal/pelvic MRI scans may be performed. Bone scans
should only be conducted when clinically indicated.
Other
Survival
inform-
ation
√
√
Subsequent
anti-
tumor therapy
√
√
pour ：
[1] All baseline assessments were based on the values closest to the time of study initiation.
[2] For subjects who failed the initial screening and subsequently underwent re-screening, the visit steps completed during the initial screening may not need to be repeated during
the re-screening phase if they meet the time limit requirements for that step prior to initiating study medication and comply with the enrollment criteria.
[3] There was a window period of ±3 days on day 1 of cycle 1.

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[4] Starting from cycle 2, testing should be performed D1±3 days or at least every 21 days per cycle 1, and more frequently if clinically indicated.
[5] Study completion/exit: If these tests/steps have been completed within 7 days of exit, they do not need to be repeated.

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[6] Safety Follow-up Period:90 days after the last dose. During this period, visits are conducted every 3 months (±7 days). The first (within 30 days after the last dose) and third
(within 90 days after the last dose) safety visits are recommended to be conducted at the research center, with one (within 60 days after the last dose) phone visit during this period,
which only requires collection of survival information, concomitant medications/treatments, and adverse events.
[7] Survival follow-up period: After the safety follow-up period, the survival follow-up period was entered. During this period, telephone follow-up was conducted every 30 days (±7
days) to collect survival information and follow-up treatment information.
[8] Irinotecan liposome (II) administration: Irinotecan liposome 56.5mg/m2,D 1, every 3 weeks (Q3W) was recommended in this study, and every 3 weeks was a 1 cycle.
[10] Temozolomide administration: Temozolomide 100 mg/m2/day for 5 days,3 weeks was recommended as 1 study cycle in this study.
[11 Bevacizumab administration: Bevacizumab 7.5 mg/kg, intravenous infusion,D 1,3 weeks was recommended in this study as 1 study cycle.

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Abbreviation
Abbreviation/Full English Name
Full Chinese name
ADR
Drug adverse reaction
AE
Adverse event
AKP
Alkaline phosphatase
ALT
Glutamate-alanine aminotransfer-
ase
ANC
Absolute neutrophil count
APTT
Activated
partial
thromboplastin
time
AST
Glutamate Aspartate Aminotrans-
ferase
BUN
Usea nitrogen
CHO
Chinese hamster ovary
CR
Complete remission
Cr
Creatinine
CRF
Case Report Form
CRP
C-reactive protein
CT
Computed Tomography
D
Sky
DCR
Disease control rate
D-Dimer，D-D
D-dimer
DLT
Dose-limiting toxicity
DoR
Duration of relief
DRQ
Question and Answer Sheet
ECOG
Eastern Tumor Cooperative Group
FIB
Fibrinogen
FT3
Free triiodothyronine
FT4
Free tetraiodothyronine
FullAnalysisSet，FAS
Complete analytic set
GCP
Good Clinical Practice (GCP)
GEM
Gemcitabine
GGT
Glutamyltranspetidase
G-CSF
Granulocyte Colony-Stimulating
Factor
HBcAb
Hepatitis B virus c antibody
HBeAb
Hepatitis B virus e antibody
HBeAg
Hepatitis B virus e antigen
HBsAb
Hepatitis B virus surface antibody
HBsAg
Hepatitis B virus surface antigen
HBV-DNA
Hepatitis B virus-DNA