Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06592417
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-04-28
Brief Title:
To Evaluate the Phase I Clinical Study of JSKN016 in Chinese Patients With Advanced Malignant Solid Tumors
Sponsor:
None
Organization:
None
Study Overview
Official Title:
To Evaluate the Phase I Clinical Study of JSKN016 in Chinese Patients With Advanced Malignant Solid Tumors
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase I open multi-center first-in-human study evaluating JSKN016 in subjects with advanced metastatic solid tumors divided into dose escalation and dose extension
Detailed Description:
A total of seven Q3W the first day of intravenous administration every 3 weeks dose groups were designed during the dose escalation period The dose groups were 05 10 20 40 60 70 and 80 mgkg respectively The DLT observation period was 21 days with accelerated titration BOIN design
The specific steps for conducting a clinical trial using the BOIN design are as follows
1 The accelerated titration is performed as follows the first patient is assigned 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 Only one patient at a time is treated and the dose-climbing process continues until the first DLT is observed or a second grade 2 toxicity is present or the highest dose is reached or a Safety Inspection Committee SMC discussion decides to end accelerated titration whichever occurs first At least two more patients are then treated on the current dose After that follow steps 2 and 3 below with at least 3 patients in each group to treat follow-up patients 3 patients in the non-accelerated titration dose group
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 Note the following
1 Elimination means the removal of current and higher doses from the trial The removed dose is a hypertoxic dose and will no longer be used to treat any newly enrolled patients
2 If the current dose is removed the dose is automatically lowered to the next lower level and administered to the subject for treatment If the lowest dose is eliminated the trial is terminated early to ensure subject safety In this case the MTD cannot be determined
3 If none of the decision conditions ie raise lower or remove the dose are met continue to treat the next group 3 subjects with the current dose
4 If the current dose is the minimum dose but the dose is still required to be reduced by the rules the new subject is still treated at the current minimum dose If the number of subjects with DLT reaches the exclusion threshold the trial is terminated early to ensure subject safety
5 If the current dose is the maximum dose but a higher dose is required by rule the new subject is treated at the current maximum dose
3 Repeat Step 2 until the set dose escalation phase has a maximum sample size of 20 or the number of evaluable subjects treated at the current dose reaches 9 and the current decision is to maintain the current dose according to the rise and fall rule of the dose escalation decision table
During dose escalation the SMC will conduct an ongoing safety assessment The safety data for each dose group is reviewed by the SMC before the next dose group is administered For the 6th dose group 7 mgkg SMC can decide whether to skip this dose group by comprehensively considering the previous safety PK and other data The composition and responsibilities of the SMC will be further detailed in the SMC Constitution
In each dose group the administration of the second subject was initiated at least 24 hours after the administration of the first subject to identify some acute toxicities such as infusion-related reactions
Allow patients to proceed with intragroup dose escalation to minimize the potential for undertreatment of patients Intrapatient dose escalation will be performed in the following manner 1 Intrapatient dose escalation will only be performed if grade 2 toxicity is observed during the previous treatment cycle 2 Does not increase to the next higher dose level until the full DLT observation period is evaluated for the next higher dose level and the SMC does not confirm safety concerns 3 Patients receiving the first dose escalation should be dosed for at least 4 cycles without disease progression For example if patients in the 1 mgkg group completed DLT observation and 4 cycles of dosing only if patients in the 2 mgkg cohort completed a complete DLT evaluation the SMC did not confirm safety concerns and no grade 2 toxicity was observed in patients in the 1 mgkg cohort during the previous treatment cycle Subsequent doses may be increased to 2 mgkg with the consent of the SMC
The recommended dose for cohort expansion RDE will be determined by the SMC based on safetytolerability 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
The specific steps for conducting a clinical trial using the BOIN design are as follows
1 The accelerated titration is performed as follows the first patient is assigned 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 Only one patient at a time is treated and the dose-climbing process continues until the first DLT is observed or a second grade 2 toxicity is present or the highest dose is reached or a Safety Inspection Committee SMC discussion decides to end accelerated titration whichever occurs first At least two more patients are then treated on the current dose After that follow steps 2 and 3 below with at least 3 patients in each group to treat follow-up patients 3 patients in the non-accelerated titration dose group
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 Note the following
1 Elimination means the removal of current and higher doses from the trial The removed dose is a hypertoxic dose and will no longer be used to treat any newly enrolled patients
2 If the current dose is removed the dose is automatically lowered to the next lower level and administered to the subject for treatment If the lowest dose is eliminated the trial is terminated early to ensure subject safety In this case the MTD cannot be determined
3 If none of the decision conditions ie raise lower or remove the dose are met continue to treat the next group 3 subjects with the current dose
4 If the current dose is the minimum dose but the dose is still required to be reduced by the rules the new subject is still treated at the current minimum dose If the number of subjects with DLT reaches the exclusion threshold the trial is terminated early to ensure subject safety
5 If the current dose is the maximum dose but a higher dose is required by rule the new subject is treated at the current maximum dose
3 Repeat Step 2 until the set dose escalation phase has a maximum sample size of 20 or the number of evaluable subjects treated at the current dose reaches 9 and the current decision is to maintain the current dose according to the rise and fall rule of the dose escalation decision table
During dose escalation the SMC will conduct an ongoing safety assessment The safety data for each dose group is reviewed by the SMC before the next dose group is administered For the 6th dose group 7 mgkg SMC can decide whether to skip this dose group by comprehensively considering the previous safety PK and other data The composition and responsibilities of the SMC will be further detailed in the SMC Constitution
In each dose group the administration of the second subject was initiated at least 24 hours after the administration of the first subject to identify some acute toxicities such as infusion-related reactions
Allow patients to proceed with intragroup dose escalation to minimize the potential for undertreatment of patients Intrapatient dose escalation will be performed in the following manner 1 Intrapatient dose escalation will only be performed if grade 2 toxicity is observed during the previous treatment cycle 2 Does not increase to the next higher dose level until the full DLT observation period is evaluated for the next higher dose level and the SMC does not confirm safety concerns 3 Patients receiving the first dose escalation should be dosed for at least 4 cycles without disease progression For example if patients in the 1 mgkg group completed DLT observation and 4 cycles of dosing only if patients in the 2 mgkg cohort completed a complete DLT evaluation the SMC did not confirm safety concerns and no grade 2 toxicity was observed in patients in the 1 mgkg cohort during the previous treatment cycle Subsequent doses may be increased to 2 mgkg with the consent of the SMC
The recommended dose for cohort expansion RDE will be determined by the SMC based on safetytolerability 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None