Study of AK112 in the Treatment of Advanced Gynecological Tumors

Study Overview
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Brief Summary
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A phase II study to evaluate the efficacy and safety of AK112 in subjects with advanced gynecological tumors.

Official Title
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Phase II Study of AK112 (Anti-PD-1 and VEGF Bi-specific Antibody) in the Treatment of Advanced Gynecological Carcinoma

Conditions
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Gynecologic Cancer, Cancer Metastatic, Ovarian Neoplasms, Cervical Neoplasm, Endometrial Neoplasms

Intervention / Treatment
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* Drug: AK112


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be able and willing to provide written informed consent 18 to 75 years old of age during enrollment Has ECOG performance status of 0 or 1 Has a life expectancy of at least 3 months Confirmed diagnosis of advanced gynaecological neoplasm Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by investigator Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue obtained from either a core or excisional tumor biopsy Has adequate organ functions (e.g hematology, renal, hepatic and coagulation) All female subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment Be able and willing to comply with all requirements of study participation (including all study procedures) Exclusion Criteria: Known history of other malignancy (in the last 5 years) except localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder carcinoma, cervical carcinoma in situ, breast carcinoma in situ that has undergone curative therapy and breast carcinoma that has not recurred for > 3 years after radical surgery Is currently participating in a study of an investigational agent or using an investigational device 4 weeks prior to first administration of study drug For patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, prior abdominal and pelvic radiation therapy was performed For recurrent/metastatic endometrial carcinoma, subjects had carcinosarcomas (malignant mixed Mullerian tumors), endometrial leiomyosarcomas or other high-grade sarcomas, or endometrial stromal sarcomas Ovarian carcinoma of non-epithelial origin, fallopian tube cancer, primary peritoneal carcinoma (e.g., germ cell tumor); Ovarian neoplasms with low malignancy potential (e.g. borderline neoplasms) Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment Previous history of immunodeficiency; HIV antibody positive; Current long-term use of systemic corticosteroids or other immunosuppressants Severe infection, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia, occurs within 4 weeks prior to the first administration of the study drug; Active infection with systemic anti-infective therapy (excluding antiviral therapy for hepatitis B or C) within two weeks prior to first administration of study drug Untreated active hepatitis B subjects; subjects with hepatitis B are required to receive anti-HBV therapy during the study period; active hepatitis C subjects Has undergone major surgery within 30 days prior to the first dose of study treatment Has known active central nervous system (CNS) metastases Previous history of myocarditis, cardiomyopathy, and malignant arrhythmia. Unstable angina, myocardial infarction, congestive heart failure, or vascular disease requiring hospitalization (such as aortic aneurysm at risk of rupture), or other cardiac impairment (such as poorly controlled arrhythmias, myocardial ischemia) that may affect study drug safety evaluation within 12 months prior to first administration of study drug Previous history of abdominal fistula or gastrointestinal perforation associated with anti-VEGF therapy; the imaging results revealed the invasion of intestinal wall by neoplasm during screening During screening, imaging or clinical findings of gastrointestinal obstruction, including incomplete obstruction Previous history of severe bleeding or coagulation disorders; during screening, imaging showed that the neoplasm surrounded major blood vessels or had obvious necrosis and cavitation, and the investigators believed that participation in the study might increase risk of bleeding Has received a live virus vaccine within 30 days prior to first administration of study drug or plan to be administered during the study period Has known psychiatric or substance abuse disorders Is pregnant, breastfeeding women Any prior or current disease, treatment, or laboratory test abnormality that may confound the study endpoints, interfere with subjects' full participation in the study, or may not be in their best interest to participate in this study

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

Sexes Eligible for Study
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Female

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advanced gynecological neoplasms<br> | Drug: AK112<br>* AK112 infusion biweekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rates (ORR) according to RECIST v1.1 in the FAS population |  | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy endpoint: disease control rate (DCR) assessed according to RECIST v1.1 |  | Up to approximately 2 years | 
| Efficacy endpoint: duration of response (DOR) assessed according to RECIST v1.1 |  | Up to approximately 2 years | 
| Efficacy endpoint: time to response (TTR) assessed according to RECIST v1.1 |  | Up to approximately 2 years | 
| Efficacy endpoint: progression-free survival (PFS) assessed according to RECIST v1.1 |  | Up to approximately 2 years | 
| Efficacy endpoint: overall survival (OS) assessed according to RECIST v1.1 |  | Up to approximately 2 years | 
| Serum PK concentrations of AK112 in individual subjects at different time points after AK112 administration |  | Up to approximately 2 years | 
| Number of subjects with detectable anti-drug antibodies (ADA) |  | Up to approximately 2 years | 
| Percentage of subjects with detectable anti-drug antibodies (ADA) |  | Up to approximately 2 years | 
| Correlation between the expression of PD-L1 and the antitumor activity of AK112 in tumor tissues |  | Up to approximately 2 years | 
| Correlation between microsatellite instability (MSI) and mismatch repair defect (DMMR) in tumor tissue samples from patients with endometrial cancer and the antitumor activity of AK112 |  | Up to approximately 2 years | 
| The association between BRCA1/2 mutation and AK112 antitumor activity in peripheral blood samples and tumor tissues from patients with epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer |  | Up to approximately 2 years |