A Study of AK112 Monotherapy in Advanced/Metastatic Renal Cell Carcinoma

A Study of AK112 Monotherapy in Advanced/Metastatic Renal Cell Carcinoma

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.

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.