A Phase I Study of JS108 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a phase I, open-label, first-in-human clinical study designed to evaluate the safety, tolerability, PK profile and efficacy of JS108 for patients with advanced solid tumors. This study is divided into 3 periods: dose escalation period, dose expansion period, and clinical expansion period.

Official Title
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A Phase I, Open-label, First-in-human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of Recombinant Humanized Anti-Trop2 mAb-Tub196 Conjugate in Patients With Advanced Solid Tumors.

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: JS108 (recombinant humanized anti-Trop2 mAb-Tub196 conjugate for injection)


Participation Criteria
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Eligibility Criteria
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Volunteer to sign an informed consent form. Age of 18-75 years (inclusive), male or female; Expected survival ≥3 months; Histological or cytologically confirmed locally advanced or metastatic solid tumors which progressed on standard of care or with no standard of care available; Toxicity of previous antitumor therapy has recovered to ≤ grade 1 as defined by the NCI-CTCAE v5.0, except alopecia; Subjects dose expansion period and clinical expansion period must have at least one measurable lesion in accordance with RECIST v 1.1; Eastern Cooperative Oncology Group (ECOG) Performance Status score: 0 or 1; Subjects must be able to provide fresh or archived tumor tissue obtained within 1 year prior to inclusion in the study； The organ function level must meet the protocol requirements； Serum pregnancy test confirmed as negative for women of childbearing potential within 7

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br> | Drug: JS108 (recombinant humanized anti-Trop2 mAb-Tub196 conjugate for injection)<br>* Dose escalation period: JS108 is administered intravenously every three weeks (Q3W) at the dose corresponding to the enrolled dose cohort. Dose expansion period: JS108 is administered intravenously Q3W at the corresponding dose. Clinical expansion period: JS108 is administered intravenously Q3W at the recommended dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD) | Number of participants that experienced dose limiting toxicities(DLTs) at given dose level. | A minimum of 21 days after first infusion of study drug | 
| Number of participants with adverse events (AEs) | The adverse events will be evaluated in accordance with CTCAE v5.0. The investigator shall assess the relationship between the events and investigational product. | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum or plasma concentration (Cmax) | One of the pharmacokinetics parameters for JS108 | Through study completion, an average of 1 year | 
| Maximum serum drug time（Tmax） | One of the pharmacokinetics parameters for JS108 | Through study completion, an average of 1 year | 
| Area under the serum or plasma concentration time curve from 0 to infinity (AUC0-inf) | One of the pharmacokinetics parameters for JS108 | Through study completion, an average of 1 year | 
| Volume of distribution at steady state (Vss) | One of the pharmacokinetics parameters for JS108 | Through study completion, an average of 1 year | 
| Terminal phase elimination half life (t½) | One of the pharmacokinetics parameters for JS108 | Through study completion, an average of 1 year | 
| Clearance (CL) | One of the pharmacokinetics parameters for JS108 | Through study completion, an average of 1 year | 
| Anti-drug antibodies (ADA) | To evaluate the immunogenicity of JS108 in patients with advanced solid tumors | Through study completion, an average of 1 year | 
| Objective Response Rate (ORR) | As determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, which will be complete response (CR) + partial response (PR) | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year | 
| Duration of response (DOR) | DOR is defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of PD or death due to any cause, whichever occurs first. | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year | 
| Progression Free Survival (PFS) | PFS is defined as the time from the date of randomization to the earlier of the dates of the first documentation of progressive disease or death due to any cause. | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year | 
| Overall Survival (OS) | OS is defined as the time from the date of randomization to the date of death due to any cause. | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year | 
| Levels of Trop2 (trophoblast antigen 2) expression in tumor tissue | To investigate any potential correlations of Trop2 levels with responses and toxicity | Through study completion, an average of 1 year |