Safety, Tolerability, PK, PD, Immunogenicity and Efficacy of TWP-102 in Patients With Advanced Malignancies.

Study Overview
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Brief Summary
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This is a multi-center, phase I, open clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and efficacy of TWP-102 injection in patients with advanced malignancies. This study consists of two parts, including a dose escalation study and a dose expansion study. The criteria for dose escalation will be based on the Bayesian optimal interval (BOIN) design with sequentially enrolled cohorts.

Official Title
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A Multi-center, Phase I, Open Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Efficacy of TWP-102 in Patients With Advanced Malignancies.

Conditions
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Advanced Malignancies

Intervention / Treatment
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* Drug: TWP-102 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed advanced malignancies that failed, or not suitable for standard treatments; At least 1 measurable lesion. ECOG score 0 or 1; Life expectancy of ≥ 3 months; Exclusion Criteria: Known hypersensitivity to any ingredient of TWP-102; Receiving any anti-cancer drugs within 4 weeks; History of serious systemic diseases; History of serious autoimmune diseases; Persistent toxicity of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade > 1 severity that is related to prior anti-cancer therapy. (except alopecia) 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: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort<br>Four dose levels of TWP-102 injection will be tested by BOIN study design. | Drug: TWP-102 injection<br>* IV infusion<br>|
| Experimental: Dose Expansion Cohort<br>Once the effective doses have been determined, two expansion cohorts will be opened to evaluate the efficacy and safety in one or two tumors. | Drug: TWP-102 injection<br>* IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events/serious adverse event related with TWP-102 injection |  | From enrollment until 90 days after the last dose | 
| Dose-limiting toxicity (DLT) |  | From the first dose of study drug up to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured plasma concentration (Cmax) of TWP-102 injection. |  | From first dose until 90 days after the last dose | 
| Time to maximum plasma concentration (Tmax) of TWP-102 injection. |  | From first dose until 90 days after the last dose | 
| Half-life (T1/2) of TWP-102 injection. |  | From first dose until 90 days after the last dose | 
| Immunogenicity profile of TWP-102 injection. | Blood samples will be collected from subjects post treatment for assessment to detect the presence of anti-drug antibodies and neutralizing antibodies. | From first dose until 90 days after the last dose | 
| Objective Response Rate (ORR) |  | 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 or end of study, 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 |