A Study of AK117/AK112 in Metastatic Triple-Negative Breast Cancer

Study Overview
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Brief Summary
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This trial is a Phase II study. The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of AK117/AK112 administered with chemotherapy in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic breast cancer (mBC).

Official Title
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A Phase II Study of AK117/AK112 in Combination With Chemotherapy for Patients With Previously Untreated Metastatic Triple-Negative Breast Cancer

Conditions
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Metastatic Triple-negative Breast Cancer, Locally Advanced Triple-negative Breast Cancer

Intervention / Treatment
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* Drug: AK117
* Drug: AK112
* Drug: Nab paclitaxel
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC Eligible for taxane monotherapy A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks, or at least 5 unstained slides with an associated pathology report documenting ER, PR, and HER2 negativity. Eastern Cooperative Oncology Group performance status of 0 or 1 Measurable disease as defined by RECIST v1.1 Adequate hematologic and end-organ function Exclusion Criteria: Known central nervous system (CNS) disease, except for asymptomatic CNS metastases Leptomeningeal disease Pregnancy or lactation History of autoimmune disease Prior allogeneic stem cell or solid organ transplantation Positive test for human immunodeficiency virus Active hepatitis B or hepatitis C Receipt of a live, attenuated vaccine within 30 days prior to randomization, during treatment

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cohort1(AK117 +AK112 +Nab-Paclitaxel/ Paclitaxel)<br>Subjects receive AK117 and AK112 Plus Nab-Paclitaxel/ Paclitaxel until disease progression or unacceptable toxicity. | Drug: AK117<br>* AK117 at a dose of 45mg/kg via intravenous (IV) infusion on Days 1,8 ,15 and 22of each 28-day cycle until disease progression or unacceptable toxicity<br>Drug: AK112<br>* AK112 at a dose of 20mg/kg via intravenous (IV) infusion on Days 1and 15 of each 28-day cycle until disease progression or unacceptable toxicity.<br>Drug: Nab paclitaxel<br>* Nab-Paclitaxel at a starting dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.<br>Drug: paclitaxel<br>* Paclitaxel at a starting dose of 90 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.<br>|
| Experimental: cohort2(AK117 +Nab-Paclitaxel/ Paclitaxel)<br>Subjects receive AK117 Plus Nab-Paclitaxel/ Paclitaxel until disease progression or unacceptable toxicity. | Drug: AK117<br>* AK117 at a dose of 45mg/kg via intravenous (IV) infusion on Days 1,8 ,15 and 22of each 28-day cycle until disease progression or unacceptable toxicity<br>Drug: Nab paclitaxel<br>* Nab-Paclitaxel at a starting dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.<br>Drug: paclitaxel<br>* Paclitaxel at a starting dose of 90 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.<br>|
| Experimental: cohort3(AK112 +Nab-Paclitaxel/ Paclitaxel)<br>Subjects receive AK112 Plus Nab-Paclitaxel/ Paclitaxel until disease progression or unacceptable toxicity. | Drug: AK112<br>* AK112 at a dose of 20mg/kg via intravenous (IV) infusion on Days 1and 15 of each 28-day cycle until disease progression or unacceptable toxicity.<br>Drug: Nab paclitaxel<br>* Nab-Paclitaxel at a starting dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.<br>Drug: paclitaxel<br>* Paclitaxel at a starting dose of 90 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rates (ORR) | ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1 | Up to approximately 2 years | 
| Number of participants with adverse events (AEs) | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) | Disease control rate (DCR) is defined as the proportion of subjects with CR, PR, or stable disease(SD) based on RECIST V1.1 | Up to approximately 2 years | 
| Duration of response (DOR) | DOR is defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response (CR or PR) to the date of disease progression per RECIST v1.1 or death from any cause, whichever occurred first | Up to approximately 2 years | 
| Time to response (TTR) | TTR is defined for participants who had an objective response as the time from the start of treatment to the first occurrence of a documented unconfirmed response (CR or PR) . | Up to approximately 2 years | 
| Progression-free survival (PFS) | PFS is defined as the time from the start of treatment till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first). | Up to approximately 2 years | 
| Overall survival (OS) | Overall survival is defined as the time from the start of treatment until death due to any cause. | Up to approximately 2 years |