A Study to Evaluate the Efficacy and Safety of AK127 in Patients With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This study is to characterize the safety, tolerability and anti-tumor activity of AK127 as a single agent in adult subjects with advanced solid tumor malignancies.

Detailed Description
-----------------
This study is to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK127 as a single agent in adult subjects with advanced solid tumor malignancies. The study, as a dose escalation phase is to determine the maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D) for AK127 as a single agent, and describe Dose Limiting Toxicity (DLT).

Official Title
-----------------
A Phase I Open-label Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of AK127 Monotherapy in Patients With Advanced Malignant Tumors

Conditions
-----------------
Advanced Solid Tumors

Intervention / Treatment
-----------------
* Drug: AK127


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. Life expectancy ≥3 months. Histologically or cytologically documented advanced or metastatic solid tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject is not suitable for standard therapy. Adequate organ function. Patients of childbearing potential must agree to use effective contraceptive measures. Exclusion Criteria: The patient has received prior immunotherapy against TIGIT target. Not currently enrolled in any other clinical study. Receipt of any anticancer therapy within 4 weeks or within 5 half-lives of the drug prior to the first dose of AK127. Symptomatic central nervous system metastases. Active malignancies within the past 1 years, with the exception of tumors in this study and cured local tumors. Active autoimmune disease requiring systemic treatment prior to the start of study treatment. There is a history of major diseases 1 year prior to the first dose. Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose. Received chest radiation therapy prior to the first dose. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis). Receipt of live or attenuated vaccination within 4 weeks prior to the first dose of AK127. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Known history of active tuberculosis. History of organ transplant or hematopoietic stem cell. History of primary immunodeficiency. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results. Other cases deemed inappropriate by the investigator.

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: AK127<br>Subjects will receive AK127 by intravenous administration | Drug: AK127<br>* Subjects will receive AK127 by intravenous administration（administered on Day 1 of each cycle, Q3W）<br>* Other names: Subjects will receive AK127 by intravenous administration;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment | From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first | 
| Number of participants with a Dose Limiting Toxicity (DLT) | DLTs will be assessed during the first 21 days of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected or definite relationship to study drug | During the first 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first assessed by investigator Per RECIST 1.1. | Up to 2 years | 
| ORR | Efficacy measures such as overall response rate (ORR), which is the proportion of subjects with CR or PR by IRRC based on RECIST v1.1 | Up to 2 years | 
| DCR | Disease control rate (DCR), which is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1 | Up to 2 years | 
| DOR | Duration of response (DoR), which is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first | Up to 2 years | 
| TTR | TTR is defined as the time to response base on RECIST v1.1 | Up to 2 years | 
| Area under the Concentration-Time Curve (AUC) of AK127 | The endpoints for assessment of PK of AK127 include serum concentrations of AK127 at different timepoints after AK127 administration | Cycle 1 and 4: Predose, Post-dose-5min,2 hours, 24 hours, Day 4,8 and 15; Cycle 2,3,5,6: Predose and Post-dose-5min; then Predose at Day 1, every 2 cycles (cycle length 21 days),Day30 after last dose; Up to 2 years and 1 months | 
| Maximum observed concentration (Cmax) of AK127 | The endpoints for assessment of PK of AK127 include serum concentrations of AK127 at different timepoints after AK127 administration | Cycle 1 and 4: Predose, Post-dose-5min,2 hours, 24 hours, Day 4,8 and 15; Cycle 2,3,5,6: Predose and Post-dose-5min; then Predose at Day 1, every 2 cycles (cycle length 21 days),Day30 after last dose; Up to 2 years and 1 months | 
| Minimum observed concentration (Cmin) of AK127 at steady state | The endpoints for assessment of PK of AK127 include serum concentrations of AK127 at different timepoints after AK127 administration | Cycle 1 and 4: Predose, Post-dose-5min,2 hours, 24 hours, Day 4,8 and 15; Cycle 2,3,5,6: Predose and Post-dose-5min; then Predose at Day 1, every 2 cycles (cycle length 21 days),Day30 after last dose; Up to 2 years and 1 months | 
| Number and Percentage of Subjects with Anti-Drug Antibodies(ADAs) to AK127 | The immunogenicity of AK127 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs) | Predose on Day 1 at Cycle 1-6, then Predose at Day 1, every 2 cycles,Day30 after last dose; Up to 2 years and 1 months |