Gentulizumab in Relapsed/Refractory Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Inclusion Criteria:

1. The patient has the willingness to communicate with the Investigator, be able tounderstand and follow the trial requirements, volunteer to participate in the trial,understands and signs the written ICF, and is willing and able to comply with thevisit schedule, administration plan, laboratory examination, and other clinical trialprocedures.
2. Gender: Male or female.
3. Age ≥18
4. Life expectancy ≥ 3 months.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
6. Patients with relapsed/refractory AML or MDS for whom there exists no standardtreatment options available.

• AML diagnosed according to the 2016 WHO classification. Patients with acutepromyelocytic leukemia (APL) are excluded. See Appendix 1.
• For the patients MDS diagnosed according to the World Health Organization (WHO)classification system and evaluated as moderate-risk, high-risk, and veryhigh-risk according to the Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndrome.

7. The white blood cell (WBC) count in the patient's peripheral blood must be ≤ 20 × 109/L within 7 days of the first dose of the study drug. The patients with WBC count > 20 × 109/L may be treated with hydroxyurea (maximum dose 4 g/d) during the Screeningperiod to achieve entry criteria. Hydroxyurea may be continued for the first 4 weeksof treatment (Cycle 1) to control blast counts at the discretion of the Investigator;hydroxyurea must be stopped after the first 4 weeks of treatment.
8. Hb levels must be above 5 g/dL on the day of the first dose of the study drug, and maybe maintained by transfusion. Transfusion is permitted in the duration of trial.
9. Platelet count ≥ 10,000 cells/uL with no evidence of medically significant bleeding ormedical predisposition to bleeding. Platelets may be maintained by transfusion at thediscretion of the Investigator.
10. Adequate liver and kidney function as evidenced by meeting the following requirements:

• Serum creatinine (Cr) ≤ 1.5 × the upper limit of normal (ULN) or creatinineclearance (CrCl) ≥ 60 mL/min (based on Cockcroft-Gault formula)
• Aspartate aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5.0 times ULN for patients with liver metastasis/infiltration)
• Serum total bilirubin (TBIL) ≤ 1.5 × ULN except for patients with Gilbert'ssyndrome, who are included if total bilirubin is < 3 × ULN or if direct bilirubinis < 1.5 × ULN.

11. Coagulation profile: prothrombin time (PT) ≤ 1.5 × ULN, international normalized ratio (INR) ≤ 1.5 × ULN or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
12. Electrolytes and uric acid need to be stable and abnormalities correctable withmedical intervention.
13. Patients must be willing to undergo bone marrow aspirates/biopsies per protocolspecifications; these will be performed per protocol schedule to evaluate patientresponse to treatment.
14. Female patients with the possibility of pregnancy must consent to practice sexualabstinence or use of two highly effective forms of contraception, from the time ofsigning the ICF until at least 24 weeks after the end of dosing. Male patients with apartner of childbearing potential must consent to practice abstinence or use of twohighly effective forms of contraception from the time of signing the ICF until atleast 24 weeks after the end of dosing.

• Note: Women who have undergone surgical sterilization (including hysterectomy,bilateral oophorectomy or total hysterectomy), or who are postmenopausal (definedas no menses for more than 12 consecutive months without medical interference)are considered to have no possibility of pregnancy.

15. Patients who have recovered from the toxic effects of the last treatment (CTCAE ≤grade1, except for special circumstances such as alopecia, fatigue) before the firstdosing, and whose corresponding AEs are judged by the Investigator as having no safetyrisks for treatment on the current study are eligible.

Exclusion Criteria:

1. Female patients who are pregnant or lactating or have a positive pregnancy test atbaseline.
2. Patients with previous severe allergic reactions to the investigational drug or itscomponents.
3. Patients who have received any of the following treatments:

• Prior treatment with the CD47/SIRPα pathway as the therapeutic target.
• Systemic antitumor therapy or any experimental therapy including within 7 days or 5 half-lives, whichever is longer, before the first dose. If a patient isreceiving cytarabine, oral fluorouracils and endocrine therapy, the patient mustbe off the drug for at least 2 weeks or until the patient has recovered fromtoxic effects. If a patient is receiving nitrosourea, mitomycin or monoclonalantibody, the patient must be off the drug for at least 6 weeks or until thepatient has recovered from toxic effects. If the elution time is insufficient dueto schedule or PK characteristics, discussion with sponsor will be needed.
• Expected to require treatment with other systemic anti-tumor therapies such aschemotherapy, immunotherapy, biotherapy or hormone therapy (except for palliativeradiotherapy) during the study.
• Prior vaccination with anti-tumor vaccines or live attenuated vaccines within 4weeks before the first dosing.
• Prior treatment with immunomodulatory drugs within 4 weeks before the first doseof study drug, except for topical, nasal and inhaled corticosteroids, orphysiologic doses of systemic steroids (i.e., ≤ 10 mg/day prednisone or itsequivalents).

4. Not Receiving any investigational drug within 4 weeks before the first administration,or participated in another clinical study at the same time except that the patientparticipated in an observational, non-intervention clinical study, or was in thefollow-up period of an intervention clinical study.
5. No allogeneic transplantation within 6 months, no active graft-versus-host disease (GVHD), not receiving immunosuppressive treatment for GVHD within 4 weeks.
6. Symptomatic central nervous system metastases or primary leukemia includingleptomeningeal disease or spinal cord compression. Patients with asymptomatic CNSdisease who are radiologically and neurologically stable ≥ 4 weeks followingCNS-directed therapy and are on a stable or decreasing dose of corticosteroids areeligible for study entry.
7. Patients with history of any active autoimmune disease, history of autoimmune disease,or disease or syndrome requiring treatment with systemic steroids or immunosuppressivemedications (dermatological conditions that do not require systemic treatment orpatients with resolved childhood asthma/allergies that do not require any interventionin adulthood; patients with a history of autoimmune-mediated hypothyroidism on astable dose of thyroxine replacement therapy may be enrolled in the study).
8. History of immunodeficiency, including a positive HIV test, and other acquired, orcongenital immunodeficiency disease.
9. History of ≥ Grade 3 thromboembolic event within the past 12 months, or currentthrombolytic or anticoagulant therapy due to high risk of thrombus.
10. History of genetic or acquired causes of bleeding or anemia.
11. With cardiovascular diseases or manifestations including:

• Congestive heart failure (NYHA class > 2).
• History of unstable angina.
• Myocardial infarction in the past 48 weeks.
• Clinically significant malignant arrhythmia (excluding atrial fibrillation andparoxysmal supraventricular tachycardia unless hemodynamically significant).
• Clinically significant QTcF prolongation (QTcF > 450 msec for males or QTcF > 470msec for females).
• Hypertension that cannot be well controlled (systolic blood pressure > 150 mmHgand diastolic blood pressure >80 mmHg), a history of hypertensive crisis, or ahistory of hypertensive encephalopathy.

12. Presence of active infection (fever that is felt to be caused by the tumor afterwork-up for infectious causes may be enrolled according to the judgment of theinvestigator).
13. Patients with active pulmonary tuberculosis infection confirmed by medical history orCT examination, or with a history of active pulmonary tuberculosis infection within 1year before enrollment, or with a history of active pulmonary tuberculosis infectionmore than 1 year ago but without curative treatment.
14. Patients with active viral hepatitis B or C confirmed by serologic examinations, ordefined as HBV-DNA > lower limit of detection or HCV-RNA > lower limit of detectionwhen the conditions cannot be evaluated by serologic examinations (chronic hepatitis Bor chronic hepatitis C can be treated with standardized antiviral therapy for stabledisease).
15. Treponema pallidum antibody positive.
16. Major surgery or significant trauma within 4 weeks prior to the first dosing. Woundand injuries must be fully recovered.
17. Previous history of drug abuse, alcoholism, or drug addiction.
18. Concurrent malignancy within 2 years prior to entry other than adequately treatedcervical carcinoma-in-situ, localized squamous cell cancer of the skin. Theinvestigators expect both primary neoplasms could benefit from the study.
19. Patients with chronic obstructive pulmonary disease (COPD) or pulmonary fibrosis.
20. Any uncontrolled intercurrent illness or condition that in the judgment of theInvestigator may endanger the patient.