Safety Study of CC312 in Adult Patients With Relapsed/Refractory CD19 Positive B-cell Hematologic Malignancies

Inclusion Criteria:

1. CD19 positive B-cell malignancies confirmed as one of the following: aggressive orindolent B-cell NHL, philadelphia chromosome-positive or -negative B-cell ALL, orB-cell CLL; patient must meet the definition of relapse/refractory beforeenrollment.

2. ECOG (Eastern Cooperative Oncology Group) performance status 0-2, life expectancy >3months；

3. Clinical laboratory values as specified below during the Screening period.

• Total bilirubin <1.5 ULN, may be elevated up to 3 x ULN if the elevation can bereasonably ascribed to the presence of metastatic disease in the liver or inpatients with documented Gilbert's Syndrome;

• ALT or AST <3ULN, may be elevated up to 5 x ULN if the elevation can bereasonably ascribed to the presence of metastatic disease in liver;

• Calculated creatinine clearance > 50 mL/min (The Cockcroft-Gault formula);

• Hemoglobin ≥ 7 g/dL;

• Neutrophil count > 1,000/mm3 for B-cell NHL patient;

• Platelet count > 75,000/mm3 for B-cell NHL patient;

• B-ALL patients must have peripheral blast count ≤ 30,000/ mm3 prior to firstdose of CC312.

• Prothrombin time-international normalized ratio (PT-INR) ≤ 1.5ULN.

4. Female patients of childbearing potential or male patients with a partner ofchildbearing potential must use one or more contraception methods from screening andcontinued during study treatment until 3 months after the last dose;

5. Ability to understand and willingness to provide written informed consent and tocomply with scheduled visits and study procedures.

Exclusion Criteria:

1. Systemic anticancer therapy within 5 half-lives of the agent or attending clinicaltrials 4 weeks prior to beginning CC312;

2. Treatment with radiotherapy within 2 weeks before the study entry;

3. Treatment with CAR-T within 3 months before the study entry;

4. Active serious infection requiring antibiotics within 14 days before study entry;

5. Patients with prior treatment with anti-CD19 directed therapies are eligible only iftheir tumor cells have been shown to express CD19 after completing the CD19-directedtherapy;

6. Patients with brain metastases or other significant neurological conditions, exceptfor brain metastases which are asymptomatic and radiologically stable without needfor steroids for 2 weeks before the first dose of CC312;

7. Treatment with corticosteroids (>10mg daily prednisone or equivalent) orimmunosuppressive medication ≤ 7 days before the first dose of CC312, with thefollowing exceptions:

• Topical, ocular, intra-articular, intranasal, or inhalational corticosteroids;

• Use of dexamethasone to reduce peripheral blast counts in ALL;

8. Vaccination with a live virus vaccine within 4 weeks prior to the study enrollment;

9. Current autoimmune disease or history of autoimmune disease with potential CNSinvolvement;

10. Known to be allergic to protein drugs or recombinant proteins or excipients in theCC312 drug formulation. Patients who experienced Grade 3 reactions that lasted < 24hmay be eligible after discussion with investigator；

11. Except for the tolerable events determined by the investigator, any toxic effects ofthe prior therapy which have not resolved to Grade 1 (CTCAE v5.0);

12. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse;

13. Cerebrovascular accident (CVA), Transient ischemic attack (TIA), myocardialinfarction (MI), unstable angina, or New York Heart Association (NYHA) class III orIV heart failure occurring within <6 months of study entry; uncontrolled arrhythmiawithin < 3 months of study entry. Patients with rate-controlled arrhythmias may beeligible for study entry at discretion of the Investigator.;

14. Major surgery < 4 weeks or minor surgery < 2 weeks prior to screening; wound must befully healed (minor surgical procedures such as catheter placement are notexclusionary criteria);

15. Existence of congenital long QT syndrome, QTcF > 450 msec (for male) or 470 msec (for female), use of cardiac pacemaker, left ventricular ejection fraction (LVEF) <50%, clinically significant arrhythmia that requires intervention, cardiac troponinI or T > 2.0 ULN, poorly controlled diabetes (HbA1c > 9%), hypertension (systolicpressure > 160 mmHg or diastolic pressure > 100mmHg), or other medical conditions asdetermined by the Investigator. Patients with stable atrial fibrillation or flutterare eligible for study entry at the discretion of the Investigator;

16. Any other serious underlying medical (e.g. active gastric ulcer, uncontrolledseizures, cerebrovascular incidents, gastrointestinal bleeding, severe signs andsymptoms of coagulation and clotting disorders, cardiac conditions), psychiatric,psychological, familial or geographical condition that, in the judgment of theInvestigator, may interfere with the planned staging, treatment and follow-up,affect patient compliance or place the patient at high risk for treatmentrelatedcomplications;

17. Concurrent malignancy < 5 years prior to entry other than adequately treatedcervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cellcarcinoma, localized prostate cancer, ductal carcinoma in situ of the breast, or <T1 urothelial carcinoma. Patients with prostate cancer that is under activesurveillance are eligible.;

18. Pregnant or nursing women.;

19. Active hepatitis B：HBsAg positive and HBV-DNA>ULN; Active hepatitis C：HCV-Abpositive and HCV-RNA>ULN；

20. Known HIV infection；

21. B-NHL patient that received autologous stem cell transplant 6 months prior to studyscreening, or historically received organ or allogeneic stem cell/bone marrowtransplant;

22. B-ALL patients that received transplantation treatment within 3 months prior toenrollment in the study.;

23. Subjects who in the judgement of the Investigator are not suited to participate inthis trial.