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

Inclusion Criteria:

(ECOG) performance status of 0 or 1;
Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade 1-3a), MCL, MZL, LPL/WM, PTCL or CBCL);

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);
Expected survival of more than 24 weeks.

Exclusion Criteria:

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

Primary central nervous system (CNS) lymphoma;
Any of the following laboratory abnormalities Absolute neutrophil count; <1.0×10^9/L, Hemoglobin <80 g/L Platelets <50 ×10^9/L

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;
International normalized ratio (INR) > 1.5 × ULN, activated partial thromboplastin time (aPTT) > 1.5 × ULN;
Serum amylase or lipase > ULN at screening or known medical history of serum amylase or lipase > ULN;
Patients with presence of second primary malignant tumors within the last 2 years;
Clinically significant history of liver disease;
Prior treatment with any PI3Kδ inhibitors;
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;
Clinically significant active infection or interstitial lung diseases (including drug induced pneumonitis);
Major surgical procedure within 4 weeks prior to initiation of study treatment;
Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less than or equal to 1, except for alopecia;
New York Heart Association (NYHA) Class II or greater congestive heart failure;
Congenital long QT syndrome or QTc >470 msec;
Currently use medication known to cause QT prolongation or torsades de pointes;
History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment;
History of stroke or transient ischemic attack within 6 months prior to initiation of study treatment;
Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease;
History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis);
Patients with ongoing chronic gastrointestinal diseases;
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.