Overview

A First-in-Human, Open Label, Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Antitumor Activity of BT02 in Patients with Advanced Solid Tumors

Eligibility

Inclusion Criteria:

1. Age ≥18 at the time of signing the informed consent form, male or female;
2. Patients must have histologically or cytologically confirmed diagnosis of advanced solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available, or standard treatment not applicable;
3. Adequate organ and hematologic function:
   1. Hematologic (without transfusion or hematopoietic stimulating factor treatment within 14 days before study treatment)
      1. Absolute neutrophil count (ANC) ≥1.5×109/L
      2. Lymphocyte count ≥ 0.5×109/L
      3. Platelet count (PLT) ≥100×109/L, PLT ≥ 80×109/L for patients with epatocellular carcinoma (HCC)
      4. Hemoglobin (Hb) ≥9.0 g/dLb) Hepatic
      5. Total bilirubin (TBIL) ≤1.5×ULN, ≤3×ULN for patients with liver metastases or skeptically gilbert's disease
      6. Alanine aminotransferase (ALT) / Aspartate; transaminase (AST) ≤ 2.5×ULN ； ≤5×ULN for patients with liver metastases;
      7. Renal
         1. Creatinine clearance rate (Ccr)>50 ml/min; (Calculated by Cockcroft-Gault formula).
         2. Coagulation
         3. International Normalized Ratio (INR) or Activated Partial Thromboplastin Time (APTT) ≤ 1.5×ULN 4. Patients must have at least measurable or evaluable lesion in phase I and measurable lesion in phase II according to RECIST 1.1(Tumor lesions that are situated in a previously irradiated area might not be considered measurable, unless there is sufficient evidence to show a clear imaging progression after radiotherapy); 5. ECOG performance status 0~1; 6. Life expectancy ≥ 3 months; 7. For Eligible patients of childbearing potential (male and female) must agree to use effective methods of birth control (hormonal or barrier method or abstinence) during the study and for at least 6 months after the last dose of study drug. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before enrollment; 8. Good compliance and be willing to follow-up visit.

Exclusion Criteria:

1. Receive treatment before study as below:
   1. Previous systematic anti-cancer therapy, including chemotherapy, radiotherapy, biological therapy, cytokine therapy, endocrine therapy, molecular targeted therapy or immunotherapy within 4 weeks prior to the first dose of study treatment, except for the following circumstances:
      1. 6 weeks for nitrosourea or mitomycin C
      2. 2 weeks or 5-halflife (whichever is longer) for oral fluoropyrimidines and small molecule targeting agents
      3. 2 weeks for traditional Chinese medicines with anti-tumor indications
      4. palliative bone directed radiotherapy
      5. erythropoietin
   2. Major elective surgery (excluding needle biopsy) was planned during the screening

      period.

   3. Patients receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the study treatment (with the exception of patients with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily). Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
   4. Patients receiving systemic immune stimulants within 4 weeks or 5-halflife (whichever is longer)
   5. Treatment with any other investigational agent within 4 weeks prior to study treatment initiation
2. Active or prior documented autoimmune disease within past 2 years (refer to Appendix

   5), which may relapse (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, Crohn's disease, etc.). Patients with vitiligo, Grave's disease, Hashimoto's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.

3. History of clinically significant cardiovascular disease:
   1. Severe heart rhythm or conduction abnormalities, such as ventricular arrhythmia that requires clinical intervention, Ⅱ-Ⅲ degree atrioventricular block, QTc interval >480 ms, etc.;
   2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other cardiovascular and cerebrovascular events of grade 3 or above occurred within the 6 months prior to the first dose of study drug
   3. New York Heart Association (NYHA) class II or greater cardiac disease or left ventricular ejection fraction (LVEF) <50%
   4. Clinically uncontrollable hypertension
4. Significant acute or chronic infections including, among others:
   1. Known history of testing positive test for human immunodeficiency virus (HIV)
   2. If the patients with active hepatitis B (Positive tests for HBsAg and HBV-DNA, or hepatitis C virus infection (Positive tests for anti-HCV or HCV-RNA) have been undergoing suitable treatment to control disease, and developing special enrollment and visit medical examination plans for them, receiving medication treatment if needed, these patients could be included.
   3. Interstitial lung disease, or obstructive pulmonary disease, or history of symptomatic bronchospasm, or Inadequate pulmonary function defined as oxygen saturation <93%, or any other active or history of significant lung disease may cause severe dyspnea
5. Prior toxicities from anti-cancer therapies have not regressed to grade ≤1 severity

   (except for those without safety risks as judged by investigators, such as alopecia, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, etc.)

6. Any prior Grade≥3 irAE while receiving immunotherapy, including anti-CTLA-4/anti-PD-L1 treatment, or any unresolved irAE > Grade 1; Known allergy or reaction to any component of the BT02 formulation;
7. Unstable brain metastasis or meningeal metastasis with clinical symptoms, which is not suitable based on the investigator's judgment;
8. Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ.
9. Vaccination within 4 weeks of the first dose of BT02 and while on study is prohibited except for administration of inactivated vaccines (e.g. inactivated influenza vaccines).
10. Patients with mental disorders or poor compliance;
11. Known alcohol or drug abuse;
12. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test within 7 days prior to the start of study drug;
13. Other severe systemic diseases or conditions that unsuitable for participating in this study in the opinion of the investigator.