A Study of HB0025 Injection in Patients With Advanced Renal Cancer

Inclusion Criteria:

• Male or female. Age ≥ 18 years.
• The subject is able to understand and willing to sign the informed consent form (ICF) ; willing and able to comply with all study procedures.
• Patients with histologically and/or cytologically confirmed advanced clear cell renalcell carcinoma (defined as more than 50% clear cell component) that is not suitablefor radical treatment or recurrence / metastasis, with or without sarcomatoidfeatures; may benefit from investigational drug therapy as judged by the investigator;and who have disease progression after receiving at least one previous systemictreatment regimen (tyrosine kinase drugs such as sunitinib, axitinib, pazopanib,sorafenib, etc., other drugs such as everolimus, excluding treatment with immunecheckpoint inhibitors) or who cannot tolerate the current standard treatment as judgedby the investigator.
• At least one measurable tumor lesion was present according to RECIST 1.1. At the samescan level of CT or MRI scan, the longest diameter of non-lymph node lesions is atleast 10 mm, and the short diameter of lymph node lesions is ≥ 15 mm. A baselineimaging assessment could be performed up to 28 days before the first dose.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
• Life expectancy ≥3 mouths
• liver function requirements:

1. Total bilirubin (TBIL) ≤ 1.5×ULN
2. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5×ULN;AST or ALT ≤5×ULN if liver metastases are present.

• Creatinine (Scr) < 1.5×ULN and Calculated creatinine clearance (CrCL) > 40 mL/ min (Cockcroft-Gault Equation).
• Hematology：

1. absolute neutrophil count (ANC) ≥ 1,500/µL. (No use of recombinant humangranulocyte colony-stimulating factor to support treatment within 14 days beforethe first administration of HB0025).
2. hemoglobin (HGB) ≥ 9 g/dL. (No transfusion or hemoglobin support within 14 daysof HB0025 first administration).
3. platelets (PLT) ≥ 75,000/µL. (No transfusion or recombinant human thrombopoietinsupport within 14 days of HB0025 first administration).

Exclusion Criteria:

• Have clinically active central nervous system (CNS) metastases. Patients withasymptomatic brain metastases who have been in a stable condition of imaging andneurological evaluation for more than 4 weeks after receiving relevant treatment willbe allowed. Patients who have undergone hormone therapy can be enrolled only if thehormone therapy dose is less than 10 mg/day prednisone or the equivalent dose of otherhormones for at least 2 weeks.
• Active autoimmune disease or history of autoimmune disease requiring systemic therapy < 2 years prior to screening except hypothyroidism, vitiligo, Grave's disease,Hashimoto's disease, or Type I diabetes. Patients with childhood asthma or atopy thathas not been active in the 2 years prior to study screening are eligible.
• History of Grade 3-4 immune-related adverse events (irAEs) or irAEs requiringdiscontinuation of prior therapies, (except for grade 3 endocrinopathy that is managedwith hormone replacement therapy).
• Use of systemic corticosteroids in a dose equivalent to >10 mg/day of prednisone orother immunosuppressive agent < 2 weeks prior to screening; the use of topical,intraocular, intraarticular, intranasal, or inhaled corticosteroids and systemicsteroids to prevent (e.g., allergy to contrast agents) or treat non-autoimmunecondition (e.g., delayed hypersensitivity caused by exposure to allergens) will beallowed.
• Cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, or New York Heart Association (NYHA) class III or IV heartfailure < 6 months of study entry; uncontrolled arrhythmia < 3 months of study entry;mean ECG QT-interval corrected according to Fridericia's formula (QTcF) > 470milliseconds (ms) (male) or QTcF > 480 ms (female) obtained from three ECGs.
• Uncontrolled diabetes, glycosylated hemoglobin HbA1c >8%；
• Those who have previously received PD-1 pathway inhibitors or cytotoxic T lymphocyteassociated antigen-4 (CTLA-4) antibodies or macromolecular vascular endothelial growthfactor (VEGF) inhibitors (such as bevacizumab, ramucirumab, etc.).
• Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) priorto study entry; palliative radiotherapy to a single area < 2 weeks prior to studyscreening is permitted. Measurable lesions cannot be previously irradiated unless theyhave demonstrated growth after radiation therapy (According to RECIST v1.1).
• Patients who have previously received allogeneic stem cell, Bone marrow or solid organtransplantation.
• Concurrent malignancy < 5 years prior to entry other than adequately treated cervicalcarcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma,localized prostate cancer, ductal carcinoma in situ of the breast, or < T1 urothelialcarcinoma.
• Any of the following infections:

1. Active infection unresolved less than 2 weeks prior to first dose of study drug.
2. Active Pulmonary tuberculosis.
3. Positive results for HIV test.
4. Active hepatitis B or C. Patients with asymptomatic hepatitis B virus carriers (HBV DNA titer < 1000 cps/mL or 200 IU/mL) or cured hepatitis C (negativehepatitis C virus RNA test) can be enrolled.

• Major surgery < 4 weeks prior to the first dose; Minor surgery < 2 weeks prior to thefirst dose.
• History of severe allergic reactions, grade 3-4 allergic reactions to treatment withanother monoclonal antibody or known to be allergic to protein drugs or recombinantproteins or excipients in HB0025 drug formulation.
• Have received or will receive a live vaccine within 30 days prior to the screening.
• Pregnant or breastfeeding women.
• Patients who have participated in any clinical trial of a drug or medical devicewithin 30 days prior to the first dose or participate in other drug clinical trials,the elution period of the test drug has not reached 5 half-lives.
• Any other serious underlying medical condition (e.g., active gastric ulcer,uncontrolled seizures, cerebrovascular incidents, gastrointestinal bleeding, severesigns and symptoms of coagulation and clotting disorders, cardiac conditions), orpsychiatric, psychological, familial condition or geographical location that, in thejudgment of the Investigator, may interfere with the planned staging, treatment andfollow-up, affect patient compliance or place the patient at high risk from treatment.
• Fertile subjects who do not want to use effective contraception during HB0025treatment and within 90 days after the last dose.
• Positive COVID-19 quantitative real time (qRT) polymerase chain reaction (PCR) orrapid screening test during screening, except for patients who turned negative 1 weekbefore administration without comorbidities and required more than 2 negative tests atintervals of not less than 72 hours.
• Patients with a history of arterial or deep vein thrombosis within 6 months beforeenrollment; evidence or history of a bleeding tendency within 2 months beforeenrollment.
• Severe dyspnea, pulmonary insufficiency or the need for continuous supportive oxygentherapy.
• Unhealed wound or ulcer; fractures from any cause within 3 months before screening
• Conditions that may cause bleeding or perforation of the digestive tract (such asduodenal ulcer, intestinal obstruction, Crohn's disease, Ulcerative colitis, largegastrectomy and small bowel resection, etc.); Patients with a history of intestinalperforation and fistula, who were not cured after surgical treatment; Esophageal andgastric varices.
• Immunomodulators, including but not limited to cyclosporine and tacrolimus, wereadministered within 2 weeks before enrollment.
• Other conditions which would make it inappropriate for the patient to participate asjudged by the investigator.
• Arterial hypertension (systolic blood pressure > 140 mmHg or diastolic blood pressure ≥ 100 mmHg) that could not be controlled even with standard treatment.
• Patients with urine protein ≥ 2 + using test strips should have 24-hour urinecollection, and patients with 24-hour urine protein content ≥ 2g.