A Phase 1 Study of SHR2554 in Subjects With Relapsed or Refractory Mature Lymphoid Neoplasms

Inclusion Criteria:

1. 18 to 70 years old (Adult, Senior)

2. Part I: Histologically or cytologically confirmed Mature lymphoid neoplasms; PartII: peripheral T cell lymphomas

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；

4. Has a life expectancy of ≥12 weeks；

5. Resistant to standard therapy or no standard therapy available，have indications fortreatment；

6. Have measurable disease （lymphoma participants，any nodes/nodal masses>1.5 cm inlongest diameter (LDi) or extralymphatic sites of disease >1.0 cm in LDi；Multiplemyeloma (MM) or Waldenström macroglobulinemia (WM) participants，serum M protein ≥0.5g/dL or Bence Jones protein≥0.2 g/24 h）. （dose expansion study must satisfy）

7. Has sufficient tumor tissue (slides or blocks) available for testing EZH2 mutationstatus and expression level. （dose expansion study must satisfy）

8. Diffuse large B-cell lymphoma (DLBCL) participants have immunohistochemistry testresults of cell origin (germinal center B-cell-like (GCB) or non-GCB), as well asmyelocytomatosis oncogene (MYC), B cell lymphoma/leukemia 2 (BCL2) and B-celllymphoma 6 (BCL6), or provide sufficient tumor tissue for testing. （dose expansionstudy must satisfy）

9. With adequate bone marrow function;

10. With adequate renal and liver function;

11. Coagulation function index：PT ≤1.5×ULN，APTT ≤1.5×ULN；

12. Women of childbearing potential (WOCBP) should be proven to be negative by humanchorionic gonadotropin (hCG) test in 7 days before the first dose of SHR2554. Theymust be willing and able to employ a highly effective method of birthcontrol/contraception to prevent pregnancy from the day they sign the informedconsent form (ICF) to at least 30 days after receiving the last dose of studytreatment. Male subjects with WOCBP partner should receive Surgical sterilization orconsent to employ a highly effective method of birth control/contraception toprevent pregnancy；

13. Any prior treatment-related clinically significant toxicities have resolved to ≤Grade 1 per CTCAE version 4.03 or prior treatment-related toxicities evaluated byphysicians are not clinically significant at time of enrollment.

14. Participant who has provided written consent to participate in the study and abilityto comply with all aspects of the protocol.

Exclusion Criteria:

1. Prior exposure to other inhibitor(s) of EZH2.

2. FL 3b or (potentially) transformed FL

3. Participants with a presence of central nerves invasion

4. Auto-transplantation within 60 days or allo-transplantation within 90 days beforethe first dose of study drug； >1 grade graft-versus-host disease (GVHD) or usingGVHD control medicines that are not allowed by this trial；

5. Major surgery or serious trauma within 4 weeks before the first dose of study drug.；

6. anti-tumor agents within 4 weeks before the first dose of study drug（such aschemotherapy, radiotherapy, immunotherapy, target therapy and other clinicalresearch）；Use of Chinese Herbal within 2 weeks before the first dose of studydrug；use of Glucocorticoids to anti tumor within 7 days before the first dose ofstudy drug（equivalent to prednisone>20 mg/d）；

7. Has known active infection with hepatitis B virus or hepatitis C virus（HBVDNA≥2×10^3 IU/mL，HCV RNA≥10^3 IU/mL）and liver dysfunction，need the intervention ofanti-virus therapy;

8. Immunocompromised (i.e. has congenital immunodeficiency), including subjects knownhistory of infection with human immunodeficiency virus (HIV) or has known activeinfection with tubercle bacillus；

9. Has an active infection or has a temperature > 38.5°C with unknownreasons（Investigators will decide the enrollment of participants with a fever thatcontributed to tumors）；

10. Has cardiovascular impairment，including history of congestive heart failure greaterthan New York Heart Association (NYHA) Class II, unstable angina, myocardialinfarction, or stroke within 1 year prior to the planned first dose of study drug;or ventricular cardiac arrhythmia requiring medical treatment；

11. abnormal of ECG with clinical significance：such as prolongation of corrected QTinterval using Fridericia's formula (QTcF)(male > 450 ms、female> 470 ms）；

12. History of cerebrovascular accident or transient ischemic attack within 6 months；

13. Has a prior malignancy other than the malignancies under study within 2 years-EXCEPTION: A subject with a history of a completely resected skin basal cellcarcinoma, skin squamous-celled carcinoma, in situ cervical cancer or other in situcarcinomas, and has been relapse-free for 5 years；

14. Has serious acute/chronic disease or psychic disease，such as suicide intention oraction in resent 1 year; or there are abnormal conditions that will increase therisk of using or managing study drug or affect the assessment of study results orinvestigator's judgment；

15. Staffs of institute sites directly related to the study or their family members,subordinates. Staffs of the sponsor pharmaceuticals company that directly related tothe study；

16. Females who are pregnant or breastfeeding.

17. Inability to take oral medication, or any uncontrolled gastrointestinal condition (e.g., active gastroenteritis, chronic diarrhea, known diverticulosis, history ofgastrectomy or gastric banding) that might impair the bioavailability of study drug.gastroesophageal reflux disease treated with proton pump inhibitors iseligible（should be no drug interaction）;

18. Use of known median or potent CYP3A4 or CYP3A5 inducers/inhibitors or P-gpinhibitors.

19. Any other major illness that, in the investigator's judgment, will substantiallyincrease the risk associated with the subject's participation in this study.