To Evaluate the Safety and Tolerability of JSKN003 in Chinese Subjects With Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

Phase I/II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of JSKN003 in Chinese Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05744427
• Other study ID #: JSKN003-102
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 15, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2023
• Source: Jiangsu Alphamab Biopharmaceuticals Co., Ltd
• Contact: Jiong Wu
• Phone: +86 13601637369
• Email: wujiong1122[@]vip.sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• JSKN003
JSKN003 should be given on the first day of administration every 3 weeks by intravenous drip.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Beijing Friendship Hospital	Beijing
China	Beijing Luhe Hospital	Beijing
China	Hunan Cancer Hospital	Changsha
China	Fujian Cancer Hospital	Fuzhou
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou
China	Sun Yat-sen University Cancer Prevention Center	Guangzhou
China	Affiliated Cancer Hospital of Harbin Medical University	Ha'erbin
China	Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	The First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Anhui Provincal Hospital	Hefei
China	Shandong Cancer Hospital	Jinan
China	Linyi City Cancer Hospital	Linyi
China	Linyi City People's Hospital	Linyi
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang
China	The Second Affiliated Hospital of Nanchang University	Nanchang
China	Gulou Hospital Affiliated to Nanjing University School of Medicine	Nanjing
China	Jiangsu Cancer Hospital	Nanjing
China	Jiangsu Provincial People's Hospital	Nanjing
China	The First Affiliated Hospital of Nanjing Medical University/Jiangsu Provincial People's Hospital	Nanjing
China	Affiliated Cancer Hospital of Guangxi Medical University	Nanning
China	Nantong Cancer Hospital	Nantong
China	Affiliated Hospital of Qingdao University	Qingdao
China	Affiliated Cancer Hospital of Fudan University	Shanghai
China	Changhai Hospital	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai
China	Shanghai East Hospital	Shanghai
China	The Second Affiliated Hospital of Soochow University	Suzhou
China	Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology	Wuhan
China	Zhongnan Hospital of Wuhan University	Wuhan
China	Xuzhou Central Hospital	Xuzhou
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Alphamab Biopharmaceuticals Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DLT (dose escalation period) in phase 1.	Incidence of dose-limiting toxicity (DLT) in dose esclation period	Up to 12 months
Primary	Maximum Tolerated Dose (MTD) in phase 1?	MTD (Maximum tolerated Dose) is the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate based on the BOIN Design	Up to 12 months
Primary	Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events in phase 1?	TEAE and SAE were gradede by CTCAE 5.0	Throughout the duration of the study, about 2 year
Primary	Objective Response Rate (ORR) in phase 2	Objective response rate (ORR) was defined as the proportion of participants who achieve either complete response [CR] or partial response [PR] per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)	Throughout the duration of the study, about 2 year
Secondary	Clinical benefit rates (CBR)	Clinical benefit rate (CR+PR+[stable disease (SD) = 6 months]) is defined as those participants with best response as CR or PR or else SD with a duration of at least 6 months. SD for 6 months duration was defined as the time from the first dose to the first documentation of PD or to the last adequate response assessment prior to data cut-off date, whichever is earlier.	Throughout the duration of the study, about 2 year
Secondary	Progression Free Survival (PFS)	PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause	Throughout the duration of the study, about 2 year
Secondary	Cmax of JSKN003	Maximum (Peak) Observed blood Concentration (Cmax) of JSKN003 Following First Dose	Throughout the duration of the study, about 2 year
Secondary	Tmax of JSKN003	Time of Maximum blood Concentration (Tmax) of JSKN003 Following First Dose	Throughout the duration of the study, about 2 year
Secondary	AUC of JSKN003	The blood PK parameters of JSKN003 and its analytes for area under the concentration-versus-time curve from time 0 to the last quantifiable concentration as calculated by the linear-up log-down trapezoidal method (AUClast) and AUC from time 0 to infinity (AUCinf) elimination rate constant associated with the terminal phase were estimated using standard non-compartmental methods.	Throughout the duration of the study, about 2 year
Secondary	Terminal Elimination Half-life (t1/2)	The blood PK parameters of Terminal elimination half-life for JSKN003	Throughout the duration of the study, about 2 year
Secondary	Anti-JSKN003 antibody	Status (positive or negative) and serum titers of anti-JSKN003 antibody	Throughout the duration of the study, about 2 year
Secondary	Duration Of Response (DOR)	Defined as the time from the first evaluation of objective response to the first evaluation of PD or death from any cause prior to PD	Throughout the duration of the study, about 2 year