A Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK114

Study Overview
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Brief Summary
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A Phase 1 study to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK114.

Detailed Description
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This is a first-in-human (FIH), Phase 1a, multicenter, open-label, single-arm dose-escalation study of AK114 to evaluate the safety, tolerability, PK, pharmacodynamics, antitumor activity and immunogenicity in adult subjects with advanced or metastatic solid tumors. The study is comprised of dose escalation phase. Approximately 30 subjects will be treated in this study.

Official Title
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A Phase 1a, Multicenter, Open-label, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK114 in Subjects With Advanced or Metastatic Solid Tumors

Conditions
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Advanced or Metastatic Solid Tumors, Malignancy, Metastasis

Intervention / Treatment
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* Drug: AK114


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written and signed informed consent Age ≥ 18 Subjects must have histologically or cytologically confirmed advanced or metastatic solid tumor Subject must have at least one measurable lesion according to RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1 At the time of Day 1 of the study, subjects with central nervous system (CNS) metastases must have been treated Available archived tumor tissue sample (block or a minimum of 10 unstained slides of formalin-fixed paraffin-embedded tissues) to allow for correlative biomarker studies Subjects may opt to provide two fresh biopsy samples (pretreatment and on treatment), where clinically appropriate Adequate organ function Use acceptable method of contraception from screening, and must agree to continue for 120 days after the final dose of investigational product Exclusion Criteria: History of severe hypersensitivity reactions to other monoclonal antibodies History or concurrent gastrointestinal perforation, surgery and wound healing complications, hemorrhage events Patients with clinically significant cardiovascular disease Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of investigational product administration Active or prior documented autoimmune disease within the past 2 years History of primary immunodeficiency History of organ transplant or hematopoietic stem cell that requires use of immunosuppressive medications Known allergy or reaction to any component of the investigational product formulation. History of interstitial lung disease or noninfectious pneumonitis except for those induced by radiation therapies. Prior treatment with canakinumab.

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Interventional Model Description: Non Randomised
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention/treatment<br>Experimental | Drug: AK114<br>* AK114 administered by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of 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 drug, whether or not considered related to the study drug. | From the time of informed consent signed through to 90 days after last dose of study drug | 
| Number of participants with a Dose Limiting Toxicity (DLTs) | DLTs will be assessed as having a suspected relationship to study drug according to pre-specific criteria in the protocol. | Within the first 28 days after receiving the first dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum pharmacokinetics (PK) | Serum concentrations of study drug in individual subjects at different time points after study drug administration | From first dose of treatment through to 90 days after end of treatment | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | The immunogenicity of study drug will be assessed by summarizing the number of subjects who develop detectable ADAs. | From first dose of study drgu through to 90 days after end of treatment | 
| Objective response rate (ORR) | The ORR is defined as the proportion of subjects with confirmed complete response (CR) or confirmed partial response (PR), based on RECIST Version 1.1. | Up to 2 years | 
| Disease control rate (DCR) | DCR is defined as the number (%) of subjects with best of response of confirmed CR or PR, or stable disease (SD) according to RECIST v1.1. | Up to 2 years |