Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas

Inclusion Criteria:

1. (ECOG) performance status of 0 or 1;
2. Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade 1-3a), MCL, MZL, LPL/WM, PTCL or CBCL);
3. Patients with relapsed or refractory NHL for whom:

   * Standard of care treatment options no longer exist (Stage 1 only);
   * Standard of care treatment options no longer exist with the exception of PI3K-delta inhibitors (Stage 2 only);
4. Expected survival of more than 24 weeks.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from study entry:

1. Primary central nervous system (CNS) lymphoma;
2. Any of the following laboratory abnormalities Absolute neutrophil count; \<1.0×10\^9/L, Hemoglobin \<80 g/L Platelets \<50 ×10\^9/L
3. Inadequate organ function, defined by the following:

   * Total bilirubin ≥1.5 times the upper limit of normal (× ULN);
   * AST or ALT \> 2.5 × ULN;
   * Estimated creatinine clearance (CrCl) per Cockcroft-Gault;
   * Dose Escalation stage of trial (Stage 1) - CrCl \< 40 mL/min;
   * Dose Expansion stage of trial (Stage 2) - CrCl \<30 mL/min;
4. International normalized ratio (INR) \> 1.5 × ULN, activated partial thromboplastin time (aPTT) \> 1.5 × ULN;
5. Serum amylase or lipase \> ULN at screening or known medical history of serum amylase or lipase \> ULN;
6. Patients with presence of second primary malignant tumors within the last 2 years;
7. Clinically significant history of liver disease;
8. Prior treatment with any PI3Kδ inhibitors;
9. Any prior use of the following: cancer therapy within 3 weeks of study treatment, GCSF within 7 days of screening, steroid therapy or targeted anti-neoplastic intent within 7 days of treatment, any use of strong CYP3A4 inducers within 2 weeks prior to initiation of study treatment, prior autologous transplant within 6 months of study treatment, prior allogenic stem cell transplant within 6 months of study treatment;
10. Clinically significant active infection or interstitial lung diseases (including drug induced pneumonitis);
11. Major surgical procedure within 4 weeks prior to initiation of study treatment;
12. Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less than or equal to 1, except for alopecia;
13. New York Heart Association (NYHA) Class II or greater congestive heart failure;
14. Congenital long QT syndrome or QTc \>470 msec;
15. Currently use medication known to cause QT prolongation or torsades de pointes;
16. History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment;
17. History of stroke or transient ischemic attack within 6 months prior to initiation of study treatment;
18. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease;
19. History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis);
20. Patients with ongoing chronic gastrointestinal diseases;
21. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.