Safety, Tolerability and Pharmacokinetics of TWP-101 in Patients With Advanced Melanoma and Urothelial Carcinoma

Study Overview
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Brief Summary
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This study is a multi-center, phase Ia/Ib, open clinical study to evaluate the safety, tolerability and pharmacokinetics of TWP-101 in patients with advanced melanoma and urothelial carcinoma. This study consists of two parts (Part A and Part B). Part A was a dose escalation study, and Part B was a dose expansion study.

Official Title
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A Multi-center, Phase Ia/Ib, Open Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TWP-101 in Patients With Advanced Melanoma and Urothelial Carcinoma

Conditions
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Advanced Melanoma, Advanced Urothelial Carcinoma

Intervention / Treatment
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* Drug: TWP-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically or cytologically confirmed advanced melanoma or urothelial carcinoma that failed, couldn't tolerate or refused standard treatments ECOG score 0 or 1; Part B: At least 1 measurable lesion according to RECIST 1.1 Exclusion Criteria: Known hypersensitivity to any ingredient of TWP-101; Receiving any anti-cancer drugs; History of serious systemic diseases; History of serious autoimmune diseases; Pregnancy or lactating women.

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort<br>Six dose levels of TWP-101 will be tested according to an accelerated titration method followed by a conventional 3 + 3 study design. | Drug: TWP-101<br>* IV infusion Q2W for 4 weeks (28-day cycles)<br>* Other names: Sytalizumab Injection;|
| Experimental: Dose Expansion Cohort<br>Once the effective dose has been determined, an expansion cohort will be opened to evaluate the efficacy and safety of the selected dose. | Drug: TWP-101<br>* IV infusion Q2W for 4 weeks (28-day cycles)<br>* Other names: Sytalizumab Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity (DLT) |  | From the first dose of study drug up to 4 weeks | 
| Incidence of adverse events and serious adverse event (defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0)) and irAE. |  | From enrollment until 90 days after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by RECIST Version 1.1 |  | From first dose to disease progression or end of study, an average of 2 years | 
| Duration of Response (DOR) |  | From first dose to disease progression, an average of 2 years | 
| Disease control rate (DCR). |  | From first dose to disease progression or end of study, an average of 2 years | 
| Progression free survival (PFS). |  | From first dose to disease progression or end of study, an average of 2 years | 
| Maximum measured plasma concentration (Cmax) of TWP-101. |  | From first dose until 90 days after the last dose | 
| Time to maximum plasma concentration (Tmax) of TWP-101. |  | From first dose until 90 days after the last dose | 
| Half-life (T1/2) of TWP-101. |  | From first dose until 90 days after the last dose | 
| Immunogenicity profile of TWP-101. | Blood samples will be collected from subjects post treatment for assessment to detect the presence of anti-drug antibodies and neutralizing antibodies by meso scale discovery(MSD). | From first dose until 90 days after the last dose |