A Study of HB0025 Injection in Patients With Advanced Renal Cancer

A Phase II, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of HB0025 in Patients With Advanced Renal Cancer

It is a phase II open label, multicenter study to assess the safety, tolerability, pharmacokinetics, and efficacy of HB0025 in patients with advanced clear cell renal cell carcinoma (ccRCC).

The phase II study will enroll subjects with advanced clear cell renal cell carcinoma (ccRCC) who have progressing tumor after standard therapy and have no better treatment option.This study will set up 2 dose groups.HB0025 injection is administered once every 2 weeks.

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 renal cell carcinoma (defined as more than 50% clear cell component) that is not suitable for radical treatment or recurrence / metastasis, with or without sarcomatoid features; may benefit from investigational drug therapy as judged by the investigator; and who have disease progression after receiving at least one previous systemic treatment regimen (tyrosine kinase drugs such as sunitinib, axitinib, pazopanib, sorafenib, etc., other drugs such as everolimus, excluding treatment with immune checkpoint inhibitors) or who cannot tolerate the current standard treatment as judged by the investigator.

• At least one measurable tumor lesion was present according to RECIST 1.1. At the same scan level of CT or MRI scan, the longest diameter of non-lymph node lesions is at least 10 mm, and the short diameter of lymph node lesions is ≥ 15 mm. A baseline imaging 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 human granulocyte colony-stimulating factor to support treatment within 14 days before the first administration of HB0025).
  2. hemoglobin (HGB) ≥ 9 g/dL. (No transfusion or hemoglobin support within 14 days of HB0025 first administration).
  3. platelets (PLT) ≥ 75,000/µL. (No transfusion or recombinant human thrombopoietin support within 14 days of HB0025 first administration).

Exclusion Criteria:

• Have clinically active central nervous system (CNS) metastases. Patients with asymptomatic brain metastases who have been in a stable condition of imaging and neurological evaluation for more than 4 weeks after receiving relevant treatment will be allowed. Patients who have undergone hormone therapy can be enrolled only if the hormone therapy dose is less than 10 mg/day prednisone or the equivalent dose of other hormones 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 that has 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 requiring discontinuation of prior therapies, (except for grade 3 endocrinopathy that is managed with hormone replacement therapy).

• Use of systemic corticosteroids in a dose equivalent to >10 mg/day of prednisone or other immunosuppressive agent < 2 weeks prior to screening; the use of topical, intraocular, intraarticular, intranasal, or inhaled corticosteroids and systemic steroids to prevent (e.g., allergy to contrast agents) or treat non-autoimmune condition (e.g., delayed hypersensitivity caused by exposure to allergens) will be allowed.

• Cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, or New York Heart Association (NYHA) class III or IV heart failure < 6 months of study entry; uncontrolled arrhythmia < 3 months of study entry; mean ECG QT-interval corrected according to Fridericia's formula (QTcF) > 470 milliseconds (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 lymphocyte associated antigen-4 (CTLA-4) antibodies or macromolecular vascular endothelial growth factor (VEGF) inhibitors (such as bevacizumab, ramucirumab, etc.).

• Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) prior to study entry; palliative radiotherapy to a single area < 2 weeks prior to study screening is permitted. Measurable lesions cannot be previously irradiated unless they have demonstrated growth after radiation therapy (According to RECIST v1.1).

• Patients who have previously received allogeneic stem cell, Bone marrow or solid organ transplantation.

• Concurrent malignancy < 5 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, localized prostate cancer, ductal carcinoma in situ of the breast, or < T1 urothelial carcinoma.

• 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 (negative hepatitis C virus RNA test) can be enrolled.

• Major surgery < 4 weeks prior to the first dose; Minor surgery < 2 weeks prior to the first dose.

• History of severe allergic reactions, grade 3-4 allergic reactions to treatment with another monoclonal antibody or known to be allergic to protein drugs or recombinant proteins 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 device within 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, severe signs and symptoms of coagulation and clotting disorders, cardiac conditions), or psychiatric, psychological, familial condition or geographical location that, in the judgment of the Investigator, may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment.

• Fertile subjects who do not want to use effective contraception during HB0025 treatment and within 90 days after the last dose.

• Positive COVID-19 quantitative real time (qRT) polymerase chain reaction (PCR) or rapid screening test during screening, except for patients who turned negative 1 week before administration without comorbidities and required more than 2 negative tests at intervals of not less than 72 hours.

• Patients with a history of arterial or deep vein thrombosis within 6 months before enrollment; evidence or history of a bleeding tendency within 2 months before enrollment.

• Severe dyspnea, pulmonary insufficiency or the need for continuous supportive oxygen therapy.

• 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 as duodenal ulcer, intestinal obstruction, Crohn's disease, Ulcerative colitis, large gastrectomy and small bowel resection, etc.); Patients with a history of intestinal perforation and fistula, who were not cured after surgical treatment; Esophageal and gastric varices.

• Immunomodulators, including but not limited to cyclosporine and tacrolimus, were administered within 2 weeks before enrollment.

• Other conditions which would make it inappropriate for the patient to participate as judged 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 urine collection, and patients with 24-hour urine protein content ≥ 2g.