a study of ak112 monotherapy in advanced/metastatic renal cell carcinoma

Conditions: Renal Cell Carcinoma

Summary: this is an open-label, single arm , ib/ii phase trial to evaluate the efficacy and safety of ak112（ivonescimab）monotherapy as first-line treatment for favourable risk advanced/metastatic renal cell carcinoma (a/m rcc). subjects will receive ak112 until disease progression, unacceptable toxic effects, death，a decision by the physician or patient to withdraw from the trial，or ak112 exposure over 2 years. the study set dose exploration stage and dose expansion stage respectively. firstly, include a few subjects for observation in dose exploration stage, and select appropriate dose to enter expansion, then continue to include more subjects to further assessment.


Eligibility criteria:
inclusion criteria: * provide written informed consent/assent for the trial. * be ≥18 and ≤ 75 years of age on day of signing informed consent, no matter male or female. * imdc favourable risk（imdc score 0）. * ecog ps 0-1. * have estimated life expectancy of at least 3 months. * have histologically or cytologically confirmed diagnosis of rcc with mainly clear cell carcinoma component. * have received no prior systemic therapy for advanced rcc，including but not limited to immunotherapy, target therapy, chemotherapy, biological therapy, etc. note: prior neoadjuvant/adjuvant therapies are acceptable if disease progression occurred \> 6 months after last dosage of neoadjuvant/adjuvant treatment. * have measurable disease per recist v1.1 . * adequate organ function. * contraception from entering the trial，until 120 days after the last administration of the investigational drug. * willing to comply with the scheduled visits, treatment plans, and other requirements of the trial. exclusion criteria: * non-clear cell renal cell carcinoma，nccrcc（e.g. chromophobe, papillary) * has active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. subjects with diabetes type i, vitiligo, psoriasis, hypo-or hyperthyroid disease not requiring immunosuppressive treatment are eligible. * has a known additional malignancy that has progressed or has required active treatment in the last 5 years. note: subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or carcinoma in situ are not excluded. * eligible for surgery. * history of severe bleeding or coagulation disorders. * history of abdominal fistula or gastrointestinal perforation related to anti vegf therapy. * has previously received systemic therapy. * has newly diagnosed brain metastases or known symptomatic brain metastases requiring steroids. * had major surgery 4 weeks prior to receiving first dose of trial treatment. * has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to receiving first dose of trial treatment. * has an active tuberculosis and syphilitic infection. * has a known history of human immunodeficiency virus (hiv) infection (hiv antibodies). * has known active hepatitis b (e.g., hepatitis b surface antigen \[hbsag\] reactive and hbv-dna\>2000 iu/ml) or hepatitis c virus (e.g., hcv rna \[qualitative\] is detected). * has been pregnant or breastfeeding. * assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Keywords: rcc，immunotherapy，ak112，first-line treatment