A Phase II Study of AK104 for Recurrent or Metastatic Vulvar Cancer

Study Overview
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Brief Summary
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This is a multicenter, open-label, phase II clinical study, aiming to the evaluate the efficacy and safety of AK104, an anti- PD-1 and CTLA-4 bispecific antibody, in subjects with recurrent or metastatic vulvar cancer not amenable to curative surgery or radiotherapy.

Official Title
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A Multicenter, Open-label, Phase II Study of AK104 in the Treatment of Recurrent or Metastatic Vulvar Cancer

Conditions
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Vulvar Cancer

Intervention / Treatment
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* Drug: AK104


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged ≥ 18. ECOG of 0 or 1. Life expectancy ≥ 3 months. Histologically confirmed vulvar cancer (squamous cell carcinoma or adenocarcinoma), not amenable to curative surgery or radical radiotherapy. Subjects who have experienced failure on at least one previous systemic therapy, or intolerance to standard therapy. At least one measurable tumor lesion per RECIST v1.1. Adequate organ function as assessed in the laboratory tests. Female subjects of childbearing potential must have a negative serum pregnancy test prior to the the first administration and agree to use effective methods of contraception Exclusion Criteria: Subjects with other histopathological types of vulvar cancer, such as melanoma, sarcoma, etc. Systemic or curative (surgery or radiotherapy) anti-tumor therapy within 4 weeks prior to the first administration. Previous treatment with immune checkpoint inhibitors (e.g., anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.). Subjects received systemic treatment with either proprietary Chinese drugs with anti-tumor indications or herbal medicines with anti-tumor effects, or immunomodulatory drugs (thymopeptide, interferon, interleukin) within 2 weeks prior to the first administration. Presence of nervous system (CNS) metastases or carcinomatous meningitis; Subjects with uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage. Clinically significant hydronephrosis that cannot be relieved by nephrostomy or ureteral stenting as judged by the Investigator. Patients with other active malignancies within 3 years prior to the first administration. Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up period of an interventional study. Major surgical treatment, open biopsy or significant trauma within 4 weeks prior to the first administration; or elective major surgical treatment required during the study. Active or potentially recurrent autoimmune disease. Subjects who require systemic treatment with glucocorticoid (> 10 mg/day of prednisone or equivalent glucocorticoid) or other immunosuppressive agents within 14 days prior to fist dose; Live or attenuated vaccination within 30 days prior to the first administration. Known primary or secondary immunodeficiencies, including testing positive for human immunodeficiency virus (HIV) antibodies. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. Known history of interstitial lung disease. Serious infections requiring hospitalization within 4 weeks prior to the first administration. Presence of active infection requiring systemic therapy. Subjects with active hepatitis B or active viral hepatitis C. Active or documented inflammatory bowel diseases or active diverticulitis. Presence of Intestinal obstruction. Any of the following cardiovascular events: -myocardial infarction, unstable angina pectoris, pulmonary embolism, aortic dissection, deep vein thrombosis or any arterial thromboembolisation events occured within 6 months prior to the first administration; -Heart function grade (New York Heart Association) ≥II; -Severe arrhythmias requiring long-term drug intervention; -Cerebrovascular event (CVA) occured within 6 months prior to the first administration; Left ventricular ejection fraction (LEVF) < 50%; -Previous history of myocarditis or cardiomyopathy; -Hypertension uncontrolled or history of hypertensive crisis. Subjects with known history of severe hypersensitivity reactions to other monoclonal antibodies. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 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: AK104<br>AK104 15mg/kg intravenously(IV) every 3 weeks (Q3W), until progressive disease, unacceptable toxicity, completion of 2 years treatment or withdrawal of consent. | Drug: AK104<br>* 15mg/kg, Q3W, IV infusion,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) assessed by investigator. | The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR per RECIST v1.1 | Up to approximately 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) Assessed by investigator | The time from the first administration to the first documented progressive disease (PD) or death due to any cause, whichever occurs first | Up to approximately 2 years | 
| Duration of Response (DOR) Assessed by investigator | Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria | Up to approximately 2 years | 
| Disease control rate (DCR) Assessed by investigator | The proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥6 weeks) based on RECIST | Up to approximately 1 years | 
| Time to Response (TTR) Assessed by investigator | The time from the first administration to the date of documented CR or PR | Up to approximately 1 years | 
| Overall survival (OS) | The time from the first administration to death due to any cause | Up to approximately 2 years | 
| Adverse Events (AEs) | Characterization of incidence, severity and abnormal clinically significant manifestation or laboratory findings. | Up to approximately 2 years | 
| serum concentrations of AK104 | assessment of PK include serum concentrations of AK104 at different timepoints after study drug administration | Up to approximately 2 years | 
| Antidrug antibodies (ADA) of AK104 | Proportion of subjects who develop detectable anti-drug antibodies (ADAs) | Up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-1/CTLA-4, vulvar cancer