A Study of AK104, a PD-1/CTLA-4 Bispecific Antibody in Subjects With Recurrent/Metastatic Cervical Cancer

Inclusion criteria

• Able to provide written and signed informed consent and any locally required authorization obtained from the subject/legal representative.
• Women aged ≥18 years at the time of study entry.
• Subjects must have histologically or cytologically confirmed recurrent or metastatic squamous carcinoma or adenosquamous carcinoma of the cervix, and meet the following criteria: disease progression confirmed by radiologic imaging during or following prior platinum based doublet chemotherapy, with or without bevacizumab for recurrent or metastatic cervical cancer; No more than 2 prior systemic therapies in the recurrent or metastatic setting.
• Subjects must have measurable lesions according to RECIST v1.1. The presence of measurable lesions must be confirmed by the IRRC. A previously irradiated lesion is not considered measurable and cannot be selected as a target lesion.
• Available archived tumor tissue sample - block or a minimum of 10 unstained slides of formalin fixed paraffin embedded [FFPE] tissues - preferably from the most recent biopsy of a tumor lesion collected either at the time of or after the diagnosis of locally advanced, recurrent, and/or metastatic disease has been made.
• Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
• Life expectancy ≥12 weeks.
• Adequate organ function.

Exclusion criteria

• Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up period of an interventional study.
• Histological types of cervical cancer other than squamous carcinoma and adeno-squamous carcinoma (eg, adenocarcinoma, small cell carcinoma, clear cell carcinoma, sarcoma, etc).
• Prior malignancy active within the previous 2 years except for the tumor for which a subject is enrolled in the study, and locally curable cancers that have been apparently cured, such as basal cell skin cancer, or carcinoma in situ of the breast.
• Brain/central nervous system (CNS) metastases.
• Clinically significant hydronephrosis, as determined by the investigator, not alleviated by nephrostomy or ureteral stent
• Active infections (including tuberculosis) requiring systemic antibacterial, antifungal, or antiviral therapy within 4 weeks prior to the first dose of investigational product.
• Known history of testing positive for human immunodeficiency virus (HIV) or known active acquired immunodeficiency syndrome.
• Known active hepatitis B or C infections (known positive hepatitis B surface antigen [HBsAg] result or positive hepatitis C virus [HCV] antibody with detectable HCV ribonucleic acid [RNA] results).
• Active or prior documented autoimmune disease that may relapse.
• History of interstitial lung disease or noninfectious pneumonitis, except for those induced by radiation therapies.
• Patients with clinically significant cardio-cerebrovascular disease.
• Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5.0 Grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of toxicities not considered a safety risk.
• History of severe hypersensitivity reactions to other mAbs.
• Prior allogeneic stem cell transplantation or organ transplantation.
• Known allergy or reaction to any component of the AK104 formulation.
• Receipt of the following treatments or procedures: anticancer small molecule targeted agent within 2 weeks, radiation therapy within 2 weeks, other anticancer therapy within 4 weeks, any major surgery within 4 weeks, any other investigational product or procedure within 4 weeks, or agents with immunomodulatory effect within 2 weeks prior to the first dose of investigational product.
• Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily doses of prednisone or equivalent) or other immunosuppressive medications within 14 days prior to the first dose of investigational product.
• Receipt of live attenuated vaccines within 30 days prior to the first dose of investigational product.
• Prior exposure to any experimental antitumor vaccines, or any agent targeting T-cell costimulation or immune checkpoint pathways (eg, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137 or anti-OX40 antibody, etc).
• Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.