A Study of AK130 in Patients With Advanced Malignant Tumors

Study Overview
=================
Brief Summary
-----------------
A Phase I open label, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of AK130 (TIGIT/TGF-β bifunctional fusion protein) in patients with advanced malignant tumors.

Official Title
-----------------
A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AK130 (TIGIT/TGF-β Bifunctional Fusion Protein) in Patients With Advanced Malignant Tumors

Conditions
-----------------
Advanced Malignant Tumors

Intervention / Treatment
-----------------
* Drug: AK130


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written and signed informed consent and any locally required authorization obtained from the subject/legal representative. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1. Life expectancy ≥3 months. Histologically or cytologically documented unresectable advanced or metastatic malignant tumor that has failed or intolerant of standard therapy, or for which no effective standard therapy is available. Subject must have at least one measurable lesion according to RECIST Version1.1. Adequate organ function. Exclusion Criteria: Any malignancy other than the disease under study within the past 3 years except for radically cured local cancers, such as basal cell skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of breast. Receipt of any anti-TIGIT, anti-TGF-β treatment. Experienced a toxicity that led to permanent discontinuation of prior immunotherapy. All AEs while receiving prior immunotherapy have not completely resolved or resolved to Grade 1 prior to screening, required the use of additional immunosuppression other than corticosteroids. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5.0 Grade 0 or 1，or to levels dictated in the inclusion/exclusion criteria, except toxicities not considered a safety risk (e.g., alopecia, neuropathy, or asymptomatic laboratory abnormalities). Major surgical procedure within 4 weeks prior to the first dose of AK130 or still recovering from prior surgery. History of organ transplant. Known allergy or reaction to any component of the AK130 formulation. History of severe hypersensitivity reactions to other mAbs.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK130<br>Each subject will receive a single dose of AK130 every 3-week cycle (Q3W) or every 2-week cycle (Q2W). Participants may continue on study drug until unacceptable toxicity, or other withdrawal criteria is met. | Drug: AK130<br>* IV infusion, specified dose on specified days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of participants with adverse events (AEs) |  | From time ICF is signed until 90 days after last dose of AK130 | 
| Number of participants with DLTs |  | During the first four weeks of treatment with AK130 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) |  | Up to approximately 2 years | 
| Disease control rate (DCR) |  | Up to approximately 2 years | 
| Progression-free survival (PFS) |  | Up to approximately 2 years | 
| Overall survival (OS) |  | Up to approximately 2 years | 
| Duration of Response (DOR) |  | Up to approximately 2 years | 
| Time to response (TTR) |  | Up to approximately 2 years | 
| Maximum observed concentration (Cmax) of AK130 | The endpoints for assessment of PK include serum concentrations of AK130 at different timepoints after AK130 administration. | From first dose of study drug through end of treatment (up to approximately 2 years) | 
| Minimum observed concentration(Cmin) of AK130 | The endpoints for assessment of PK include serum concentrations of AK130 at different timepoints after AK130 administration. | From first dose of study drug through end of treatment (up to approximately 2 years) | 
| Area under the curve (AUC) of AK130 for assessment of pharmacokinetics | The endpoints for assessment of PK include serum concentrations of AK130 at different timepoints after AK130 administration. | From first dose of study drug through end of treatment (up to approximately 2 years) | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) |  | From first dose of study drug through 30 days after last dose of study drug |