A Phase I Study of BR108 in Hematological Malignancies

Inclusion Criteria:

• 1. Voluntary agreement to provide written informed consent;
• 2. Males and females who are ≥18 years old;
• 3. Patients must have an advanced hematologic malignancy including： Relapsed orrefractory lymphoma as defined by World Health Organization(WHO) criteria； Relapsed orrefractory AML /MDSas defined by World Health Organization (WHO) criteria；
• 4. Subjects must have documented CD70-positive .
• 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• 7. Expected survival time ≥3 months;
• 8.Have at least 1 evaluable lesion per Lugano 2014;
• 9. The function of major organs must meet the following criteria (Lymphoma：have notreceived blood transfusion, EPO, G-CSF or other medical supportive treatment within 7days before the first dose of study drug) ：
• White blood cell count≤25×109/L（for AML/MDS）
• Absolute neutrophil count (ANC) ≥1.5×109/L or ≥0.75×109 /L for patients with bonemarrow infiltration, Platelet ≥75×109 /L or ≥50×109 /L for patients with bonemarrow infiltration; Hemoglobin ≥8.0mmol/L or ≥ 7.0mmol/L for patients with bonemarrow infiltration;
• International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN; ActivatedPartial Thromboplastin Time (APTT) ≤1.5×ULN;
• serum creatinine≤1.5×ULN or Creatinine clearance rate ≥60 mL/min ;
• Total bilirubin ≤1.5×ULN or ≤3×ULN for patients with Gilbert's syndrome or livermetastasis； Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5×ULN or ≤5×ULN for patients with liver metastasis:
• 10. Women of child bearing potential and non-sterilized male patients who are sexuallyactive with a female partner of child bearing potential must agree to use an effectivemethod of contraception from screening until 6 months after the last dose of studydrug. Effective methods of contraception consist of prior sterilization, intrauterinedevice, intrauterine hormone-releasing system, oral or injectable contraceptives, andsexual abstinence.
• 11. Patients will be able to communicate well with the investigator, understand andcomply with the requirements of the study.

Exclusion Criteria:

• 1. Pregnant or lactating women;
• 2. Acute promyelocytic leukemia, acute transformation of chronic myeloid leukemia,primary central nervous system malignancies or invasion of the central nervous system (except for those who are asymptomatic or stable and do not require treatment ≥4 weeksbefore the first dose of study drug);
• 3. Has not recovered from adverse reactions caused by previous anti-tumor treatmentsto ≤ grade 1 or baseline (refer to NCICTCAE5.0 ), except for alopecia, pigmentationand other toxicity judged no safety risk by the investigator;
• 4. Previous exposure to CD70-targeted agents;
• 5. Patients with Allergic history or hypersensitivity reaction to any components ofBR108 injection;
• 6. Patients with active bacterial, viral, fungal, mycobacterium, parasite or otherinfection (except fungal infection of nail bed) within 7 days prior to enrollment andrequiring intravenous infusion therapy (except neoplastic fever);
• 7. Patients with inherited or acquired hemorrhagic diseases or severe coagulationabnormalities of clinical significance（ Such as diffuse intravascular coagulation (DIC) autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, sickle cellanemia, etc）;
• 8. HBsAg or HBcAb positive, and HBV DNA positive; HCVAb positive and HCV RNA positive;HIV positive; syphilis infection requiring systematic treatment ;
• 9. Subjects who have received live or attenuated vaccine within 4 weeks before thefirst administration or planned to receive live vaccine during the study period;
• 10. History of any other malignancies within 3 years (except for basal cell carcinomaof the skin, squamous cell carcinoma of the skin, superficial bladder cancer,localized prostate cancer, cervical carcinoma in situ, stage I ductal carcinoma insitu of the breast, and malignancies that have been cured (CR) within 2 years prior toinitial administration and are currently considered stable by the investigator withminimal risk of recurrence);
• 11. Patients with serious cardiovascular and cerebrovascular diseases or other seriousorganic diseases, including but not limited to:
• History of stroke 、intracranial hemorrhage 、unstable angina pectoris、 congestiveheart failure (NYHA III-IV)、myocardial infarction、severe arrhythmias (e.g.,persistent ventricular tachycardia, ventricular fibrillation) or congenital longQT syndrome within 6 months before enrollment.
• Left ventricular ejection fraction （LVEF） < 50% in echocardiography (ECHO) ormuti-gate detection scan (MUGA) .
• Corrected QT interval prolongation >470ms.
• Patients with interstitial lung disease, severe lung dysfunction, severepulmonary fibrosis, or pulmonary infection requiring systematic treatment.
• 12. Subjects who have autoimmune disorders and need to rely on immunosuppressivetherapy or receive systemic therapy with a dose of ≥20mg/day of prednisone or otherequivalent hormones within 2 weeks before enrollment;
• 13. Patients have received other clinical trials within 4 weeks before the first doseof study drug;
• 14.Subjects who have major surgery or severe trauma within 4 weeks prior to initialdosing or plan to take major surgery during the trial period;
• 15. Treatment with prior anti-cancer therapy (including chemotherapy, endocrinetherapy, targeted therapy, etc.) must have been terminated at last 28 days or 5half-lives (whichever is shorter) before study enrolment,2 weeks for endocrine therapyand Chinese medicine treatment with anti-tumor indications or local palliativeradiotherapy for bone metastasis and pain relief within 2 weeks.
• 16. Prior allogeneic hematopoietic stem cell or organ transplantation; recentAutologous hematopoietic stem cell transplantation（less than 3 months prior firstdosing of study drug）;
• 17. Patients with any mental or cognitive impairment that may restrict theunderstanding and implementation of the informed consent;
• 18. Other serious, uncontrollable concomitant diseases that may affect protocolcompliance or interfere with outcomes, or other serious or uncontrollable medicalconditions that the investigator believes may put subjects at risk for participatingin the study