NCT06592417

To Evaluate the Phase I Clinical Study of JSKN016 in Chinese Patients With Advanced Malignant Solid Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 140 (estimated)
• Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 0.5, 1.0, 2.0, 4.0, 6.0, 7.0 and 8.0 mg/kg, 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 (i.e., 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 mg/kg, 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 mg/kg group completed DLT observation and 4 cycles of dosing, only if patients in the 2 mg/kg 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 mg/kg cohort during the previous treatment cycle. Subsequent doses may be increased to 2 mg/kg with the consent of the SMC. 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.

Conditions

• Advanced Malignant Solid Tumor

Interventions

Type	Name	Description
DRUG	JSKN016 injection	JSKN016 is a bispecific antibody drug conjugate targeting HER3 and TROP2.

Timeline

• Start date: 2024-04-30
• Primary completion: 2026-05-17
• Completion: 2026-12-31
• First posted: 2024-09-19
• Last updated: 2024-09-19

Locations

2 sites across 1 country: China