Efficacy and Safety of SHC014748M in Patients With Relapsed or Refractory Follicular (FL) or Marginal Zone (MZL) Lymphoma

Inclusion Criteria:

• Adult, male and female volunteers, above 18 years of age inclusive.
• Histologically or cytologically confirmed diagnosis of relapsed or refractory FL(grade 1, 2 or 3a) and MZL, including splenic marginal zone lymphoma(SMZL), nodal marginalzone B cell lymphoma(NMZL) and mucosa associated lymphoid tissue(MALT) lymphoma.Relapse refers to disease progression after adequate treatment to remission；refractoryrefers to no remission after adequate treatment. The above "remission" includescomplete remission and partial remission. Adequate treatment refers to two or moretreatments with CD20 monoclonal antibody (CDE approved for marketing) combined withalkylation agent, including but not limited to bendamustine, cyclophosphamide,ifosfamide, chlorambucil, melphalan, busulfan and nitrosoureas.
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
• Life expectancy ≥ 3 months.
• Patients have at least 1 measurable lesion that measures ≥1.5 cm in a single dimensionas assessed by CT or MRI.
• Adequate organ function, as defined by the following values:ANC≥1.0×10^9/L；PLT≥50×10^9/L;Hb≥80 g/L;TBIL≤2×ULN(TBIL>2×ULN for subjects with Gilbertsyndrome,TBIL>3×ULN for subjects with focal compression of bile duct judged byinvestigators); ALT and AST≤2.5×ULN(ALT and AST≤5×ULN for subjects with impaired liverfunction caused by hepatic infiltration);blood urea nitrogen(BUN) andCr≤1.5×ULN;LVEF≥50%;QTcF <450 ms for male, QTcF <470 ms for female.
• Men and women of childbearing potential are willing to employ an effective method ofcontraception for the entire duration of study and 6 months after the last dose, andfemale subjects of childbearing potential have a negative pregnancy test at baseline.
• Subjects did not participate in other clinical trials within 1 month prior to studyentry.
• Provision of signed and dated, written informed consent prior to any study-specificevaluation.

Exclusion Criteria:

• Previous treatment with any PI3Kδ inhibitors.
• Evidence of aggressive lymphoma(suspected clinical transformation should be conformedby biopsy).
• Had any other anti-tumor treatment within 4 weeks prior to screening(includingradiotherapy, chemotherapy, Chinese herbal anti-tumor treatment and major surgery);targeted therapy with 5 half-life period prior to screening.
• Evidence of central nervous system involvement of the malignancy.
• Evidence of severe or uncontrolled systemic diseases, including uncontrolledhypertension, active bleeding diatheses, uncontrolled pleural effusion and ascites,uncontrolled diabetes, severe or debilitating lung disease.
• Any of the severe heart diseases, including New York Heart Association (NYHA) Class IIor greater heart failure, arrhythmias requiring medical treatment, and history ofmyocardial infarction or unstable angina within 6 months prior to screening.Requiringany concomitant medication known to prolong the QT interval within 5 half-life period.
• Evidence of active bacterial, fungal, or viral infection, and need systemic treatment.
• Active infection with hepatitis B virus (HBV) (HBsAg positive, or HBsAg negative andHBV-DNA positive), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
• Concomitant use of any strong inhibitors or inducers of CYP3A4(except drug withdrawalprior to first dose of investigational drug.
• Use of granulocyte colony-stimulating factor(G-CSF) or blood transfusion within 7 daysbefore the hematology test at screening.
• Prior autologous hematopoietic stem cell transplantation within 3 months prior toscreening.
• History of immune deficiency(acquired and congenital), or history of organtransplantation, or allogeneic bone marrow or hematopoietic stem cell transplantation;with active autoimmune disease or history of autoimmune disease including Interstitialpneumonia, autoimmune enteritis, autoimmune hepatitis and systemic lupus erythematosus
• History of any uncured malignant tumor in the past five years except for thefollowing: clinically cured cervical or breast carcinoma in situ, local basal cell orsquamous cell carcinoma of the skin, thyroid tumor.
• Inability to swallow the drug, or history of diseases affecting gastrointestinalfunctions significantly including malabsorption syndrome,bariatricsurgery,inflammatory bowel disease, partial or complete intestinal obstruction.
• Adverse events occurred during previous anticancer therapy have not been recovered to ≤1(CTCAE 5.0).
• History of hypersensitivity to the main composition or any inactive excipient of thestudy drug.
• Women who are breastfeeding.
• With alcohol or drug abuse disorder.
• History of stroke or intracranial hemorrhage with 6 months prior to screening.
• Attenuated live vaccination within 4 weeks prior to screening.
• With basic medical condition leading to risk of taking study drugs judged byinvestigators, or with confusion to toxicity and adverse events.
• Judgment by the investigator that the patient should not participate in the study.