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

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.