Study of AK119 Combined With AK112 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a Phase Ib/II study to assess the safety, tolerability and preliminary efficacy of AK119 combined with AK112 in patients with advanced solid tumors.

Official Title
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An Open-label, Multicenter, Phase Ib/II Study to Evaluate the Safety, Tolerability and Antitumor Activity of AK119 in Combination With AK112 in Patients With Advanced Solid Tumors

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Drug: AK119
* Drug: AK112


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily written informed consent and agree to comply with all protocol-specified procedures and follow-up evaluations Age ≥ 18 years and ≤ 75 years Histologically or cytologically-confirmed diagnosis of advanced/unresectable solid tumor that have been progressed or intolerant to at least one standard treatment regimen in the advanced or metastatic setting, if such a therapy exists Measurable lesion based on RECIST v1.1 ECOG status of 0 or 1 Life expectancy ≥ 3 months Adequate organ function Women of childbearing potential and men with female partners of childbearing potential must agree to use effective contraception during treatment and for at least 120 days following the last dose of study treatment Exclusion Criteria: Known other active malignancy within 3 years prior to the first dose of investigational product, with the exception of early stage cancers that have treated with curative intent Currently participating in another study unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study Received systemic antineoplastic therapy ( e.g. chemotherapy, radiotherapy, immunotherapy) within 4 weeks prior to the first dose of investigational product; received small-molecule anticancer agents within 2 weeks prior to the first dose of investigational product In addition to anti-PD-(L)1 monoclonal antibody, prior exposure to other immune checkpoint inhibitors or any other treatment directed to tumor immune mechanism Prior therapy targeting CD73 or CD39 or the adenosine signalling pathway Treatment with non-steroidal anti-inflammatory drugs, anti-platelet agents or anticoagulants within 7 days prior to the first dose of investigational product Current dependency on systemic therapy with glucocorticoids (>10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of investigational product Presence of spinal cord compression or active brain metastases Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage History or presence of a serious hemorrhage or known bleeding tendency within 3 months Active autoimmune disease that has required systemic treatment in past 2 years Clinically significant cardiovascular disease History of interstitial lung disease or noninfectious pneumonitis Received systemic anti-infective therapy (excluding antiviral therapy for hepatitis B or C) within 14 days prior to the first dose of investigational product Major surgical procedure or serious trauma within 28 days prior to the first dose of investigational product History of immunodeficiency, human immunodeficiency virus infection (HIV) Active tuberculosis or syphilis infection History of organ transplantation or allogeneic haematopoietic stem cell transplantation Toxicities of prior anticancer therapy have not resolved to ≤ Grade 1 (NCI-CTCAE version 5.0) Any other conditions that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results

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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK119 in combination with AK112<br>AK119 and AK112, IV, every 3 weeks | Drug: AK119<br>* AK119 is an anti-CD73 monoclonal antibody.<br>Drug: AK112<br>* AK112 is a bispecific monoclonal antibody against VEGF and PD-1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with dose limiting toxicities (DLTs) | DLTs will be assessed during the first three weeks of treatment. DLTs are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the DLT observation period. | During the first three weeks | 
| Number of subjects with adverse events (AEs) | AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment. | From the time of informed consent signed through 90 days after the last dose of study drug. | 
| Objective Response Rate (ORR) | ORR is defined as the proportion of subjects with CR or PR (based on RECIST Version 1.1). | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | PFS is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first (based on RECIST Version 1.1). | Up to 2 years | 
| Disease control rate (DCR) | DCR is defined as the proportion of subjects with CR, PR, or SD (based on RECIST Version 1.1). | Up to 2 years | 
| Duration of response (DoR) | Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first. | Up to 2 years | 
| Time to response (TTR) | Time to response (TTR) is defined as the time from the start of the treatment to the first objective tumor response observed for patients who achieved CR or PR (based on RECIST Version 1.1). | Up to 2 years | 
| Time to progression (TTP) | Time to progression (TTP) is defined as the time from the start of the treatment to the documentation of disease progression (based on RECIST Version 1.1). | Up to 2 years | 
| Overall survival (OS) | OS defined as the time from the first dose to death from any cause. | Up to 2 years |