Trial Title:
To Evaluate the Safety and Tolerability of JSKN003 in Chinese Subjects With Advanced Solid Tumors
NCT ID:
NCT05744427
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
JSKN003
Description:
JSKN003 should be given on the first day of administration every 3 weeks by intravenous
drip.
Arm group label:
Dose escalation and expansion period
Arm group label:
cohort 1 in phase II
Arm group label:
cohort 2 in phase II
Arm group label:
cohort 3 in phase II
Arm group label:
cohort 4 in phase II
Arm group label:
cohort 5 in phase II
Summary:
This is an open, multicenter study of stage I/II in Chinese subjects with unresectable
locally advanced/metastatic solid tumors. It is divided into dose escalation period and
cohort expansion period. A total of 9 dose groups (Q3W on the first day of intravenous
administration every three weeks) were designed in the dose escalation period. The
initial dose was 1.0mg/kg, Q3W, and the observation period of DLT was 21 days. In the
dose expansion phase, 5 cohorts were set up.
Detailed description:
A total of nine (Q3W, the first day of intravenous administration every three weeks) dose
groups were designed in the dose escalation period. The dose groups were 1.0, 2.1, 4.2,
5.3, 6.3, 7.3, 8.4, 9.4 and 10.5 mg/kg, respectively. The BOIN design with accelerated
titration was used, and the DLT observation period was 21 days.
The specific steps for conducting a clinical trial using the BOIN design are as follows:
1. Perform the accelerated titration as follows: Assign the first patient to dose level
1. If this patient does not develop dose-limiting toxicity (DLT), the second patient
will be treated at the next higher dose level. Treat one patient at a time and
continue the dose-climbing process until the first DLT is observed, or a second
grade 2 toxicity occurs, or the highest dose is reached. Two more patients were then
treated on the current dose. After that, follow steps 2 and 3 and take the number of
cases in each group as 3 to treat the follow-up patients.
2. Assign the dose to the next group of subjects according to the dose rise and fall
rule shown in the Bayesian Optimal interval (BOIN) decision table.
3. Repeat Step 2 until the set maximum sample size of 45 or the number of evaluable
subjects treated at the current dose reaches 12 and the current decision is to
maintain the current dose according to the rise and fall rule of the dose rise and
fall decision table.
After the dose escalation period was completed, order preserving regression was used to
determine MTD. Once MTDS have been identified and the maximum sample size of 45 patients
has not been reached, sponsors may enroll up to 12 additional patients in the selected
MTDS to obtain more information on the safety and efficacy of the selected dose. In the
additional extension process, the cull boundary in the decision table is used for
toxicity monitoring.
The Safety Monitoring Committee (SMC) will conduct an ongoing safety assessment during
the dose escalation period. The safety data of each dose group should be reviewed and
decided by the SMC before starting the administration of the next dose group. If
additional safety, efficacy, and PK data are required for a dose group by SMC resolution,
subjects will be allowed to continue to be enrolled in this dose group after completing
the BOIN dose increment; If the SMC has decided that a dose group can proceed to the
cohort extension phase, it is permitted to proceed directly to the cohort extension phase
in that dose group (i.e. to Phase Ib). The composition and responsibilities of the SMC
will be further detailed in the SMC Constitution.
The recommended dose for cohort expansion (RDE) will be determined by the SMC based on
safety/tolerability, PK data, and preliminary antitumor activity, as well as other
available data. RDE can be at the same dose level as MTD or at a lower dose level than
MTD; Rdes may also be different for different indications.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Subject is at least 18 years old, male or female, and willing to follow the study
procedure on the date of signing the informed consent;
2. ECOG score 0 or 1, expected survival ≥12 weeks;
3. Unresectable locally advanced or metastatic solid tumors with pathologic documented
confirmation.
4. Measurable lesions at baseline according to RECIST 1.1 criteria; If the subject has
only one measurable lesion at baseline, the lesion area must not have received prior
radiotherapy or there is evidence of significant progression after the end of
radiotherapy.
5. Agrees to provide adequate paraffin sections or fresh tissue specimens of the tumor
for testing;
6. Laboratory tests within 7 days or cardiac ultrasound within 28 days prior to the
first dose meet the protocol criteria.
7. Adequate washout from prior therapy prior to the first dose.
8. A fertile female subject or a fertile male subject with a+B72 fertile partner agrees
to use highly effective contraception (annual failure rate less than 1%) from the
time of initial dosing to 180 days after the end of dosing. Pregnancy test results
must be negative for fertile female subjects within 7 days prior to initial
administration (fertile women are defined as premenopausal women with no recorded
tubal ligation or hysterectomy, or women who have been menopausal for less than 1
year);
Exclusion Criteria:
1. Subjects with untreated active brain metastases or meningeal metastases;
2. Previous history of other primary malignant tumors;
3. Previously received topoisomerase I inhibitor antibody conjugate drug;
4. Has uncontrolled comorbidities as specified by the protocol;
5. Past or current history of interstitial pneumonia/lung disease requiring systemic
hormonal therapy, or suspected interstitial pneumonia/lung disease that cannot be
ruled out by imaging during screening;
6. Subjects with uncontrolled large serous cavity effusion or moderate to large serous
cavity effusion requiring repeated drainage (recurrent within 2 weeks after
intervention) such as pleural effusion, pericardial effusion, ascites, bad fluid,
etc.;
7. Toxicity of previous antitumor therapy did not return to class 1 as defined by
NCI-CTCAE v5.0.
8. Systemic corticosteroids (≥10 mg/ day of prednisone, or equivalent of other
corticosteroids) or immunosuppressant therapy were required within 14 days prior to
initial administration in this study; 9. Has a history of life-threatening
anaphylaxis or known hypersensitivity to any component or excipient in the JSKN003
drug formulation.
10. Previous history of trastuzumab-induced anaphylaxis (grade ≥3), angioedema, or
severe hypotension.
11. Subjects with gastrointestinal tumors who are known to have lost 10% or more of
their body weight within three months prior to signing the informed consent form.
12. Other conditions that the investigator considers unsuitable to participate in this
clinical trial, including but not limited to psychiatric disorders, alcoholism or
drug abuse, etc.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Cancer Hospital
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Lin Shen
Facility:
Name:
Beijing Friendship Hospital
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Banwei Cao
Facility:
Name:
Beijing Luhe Hospital
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Dong Yan
Facility:
Name:
Hunan Cancer Hospital
Address:
City:
Changsha
Country:
China
Status:
Recruiting
Contact:
Last name:
Dihong Tang
Facility:
Name:
Fujian Cancer Hospital
Address:
City:
Fuzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
An Lin
Facility:
Name:
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Jieqiong Liu
Facility:
Name:
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Qunxian Rao
Facility:
Name:
Sun Yat-sen University Cancer Prevention Center
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Chunyan Lan
Facility:
Name:
Affiliated Cancer Hospital of Harbin Medical University
Address:
City:
Ha'erbin
Country:
China
Status:
Recruiting
Contact:
Last name:
Qingyuan Zhang
Facility:
Name:
Run Run Shaw Hospital, Zhejiang University School of Medicine
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Xian Wang
Facility:
Name:
The First Affiliated Hospital of Zhejiang University School of Medicine
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Jian Ruan
Contact backup:
Last name:
Xiaochen Zhang
Facility:
Name:
The Second Affiliated Hospital of Zhejiang University School of Medicine
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Jian Huang
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Yaqing Chen
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Jieer Ying
Facility:
Name:
Anhui Provincal Hospital
Address:
City:
Hefei
Country:
China
Status:
Recruiting
Contact:
Last name:
Yueying Pan
Facility:
Name:
Shandong Cancer Hospital
Address:
City:
Jinan
Country:
China
Status:
Recruiting
Contact:
Last name:
Bo Liu
Facility:
Name:
Linyi City Cancer Hospital
Address:
City:
Linyi
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhen Li
Facility:
Name:
Linyi City People's Hospital
Address:
City:
Linyi
Country:
China
Status:
Recruiting
Contact:
Last name:
Guixiang Weng
Contact backup:
Last name:
Zhongmin Zhang
Facility:
Name:
The First Affiliated Hospital of Henan University of Science and Technology
Address:
City:
Luoyang
Country:
China
Status:
Recruiting
Contact:
Last name:
Xinshuai Wang
Facility:
Name:
The Second Affiliated Hospital of Nanchang University
Address:
City:
Nanchang
Country:
China
Status:
Recruiting
Contact:
Last name:
Anwen Liu
Facility:
Name:
Gulou Hospital Affiliated to Nanjing University School of Medicine
Address:
City:
Nanjing
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jia Wei
Facility:
Name:
Jiangsu Cancer Hospital
Address:
City:
Nanjing
Country:
China
Status:
Recruiting
Contact:
Last name:
Bo Shen
Facility:
Name:
Jiangsu Provincial People's Hospital
Address:
City:
Nanjing
Country:
China
Status:
Recruiting
Contact:
Last name:
Yongqian Su
Facility:
Name:
The First Affiliated Hospital of Nanjing Medical University/Jiangsu Provincial People's Hospital
Address:
City:
Nanjing
Country:
China
Status:
Recruiting
Contact:
Last name:
Yongmei Yin
Facility:
Name:
Affiliated Cancer Hospital of Guangxi Medical University
Address:
City:
Nanning
Country:
China
Status:
Recruiting
Contact:
Last name:
Li Li
Facility:
Name:
Nantong Cancer Hospital
Address:
City:
Nantong
Country:
China
Status:
Recruiting
Contact:
Last name:
Lei Yang
Facility:
Name:
Affiliated Hospital of Qingdao University
Address:
City:
Qingdao
Country:
China
Status:
Recruiting
Contact:
Last name:
Wenfeng Li
Facility:
Name:
Affiliated Cancer Hospital of Fudan University
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Xiaohua Wu
Facility:
Name:
Changhai Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Gang Jin
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
jian zhang, professor
Phone:
+8618017312991
Email:
syner2000@163.com
Facility:
Name:
Shanghai East Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Qun Li
Facility:
Name:
The Second Affiliated Hospital of Soochow University
Address:
City:
Suzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhixiang Zhuang
Facility:
Name:
Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Country:
China
Status:
Recruiting
Contact:
Last name:
Yanxia Zhao
Facility:
Name:
Zhongnan Hospital of Wuhan University
Address:
City:
Wuhan
Country:
China
Status:
Recruiting
Contact:
Last name:
Jing Dai
Facility:
Name:
Xuzhou Central Hospital
Address:
City:
Xuzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Xiang Wang
Facility:
Name:
The First Affiliated Hospital of Zhengzhou University
Address:
City:
Zhengzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Hong Zhong
Start date:
March 15, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Jiangsu Alphamab Biopharmaceuticals Co., Ltd
Agency class:
Industry
Source:
Jiangsu Alphamab Biopharmaceuticals Co., Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05744427