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, MZL, LPL/WM, and MCL.) 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 <1.5×10^9/L, Hemoglobin <90 g/L Platelets <100 ×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 < 50 mL/min - Dose Expansion stage of trial (Stage 2) - CrCl <30 mL/min 4. Clinically significant history of liver disease, 5. Prior treatment with any PI3Kδ inhibitors 6. 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, 7. Clinically significant active infection 8. Major surgical procedure within 4 weeks prior to initiation of study treatment; 9. Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less than or equal to 1, except for alopecia; 10. New York Heart Association (NYHA) Class II or greater congestive heart failure 11. Congenital long QT syndrome or QTc >470 msec; 12. Currently use medication known to cause QT prolongation or torsades de pointes 13. History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment; 14. History of stroke or transient ischemic attack within 6 months prior to initiation of study treatment; 15. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease; 16. History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis); 17. History of drug induced pneumonitis
This is a Phase 1, open-label, multicenter study of HMPL-689 administered orally to patients
with relapsed or refractory lymphoma.
This study will consist of a dose escalation stage (Stage 1) and a dose expansion stage
Dose Escalation Stage (Stage 1):
This stage will end when any of the following criteria is met:
- The dose level 1 demonstrates an excessive toxicity, ie, 3 dose limiting toxicities
(DLTs) are observed out of the first 3 patients at dose level 1.
- The maximum sample size is reached.
- The MTD and/or RP2D is confirmed.
Dose Expansion Stage (Stage 2):
To further characterize the safety and explore the preliminary anti-tumor activity of
HMPL-689 at RP2D, patients with B cell lymphoma will be enrolled in the dose expansion stage.
Trial Phase Phase I
Trial Type Treatment
Hutchison Medipharma Limited
- Primary ID 2018-689-00US1
- Secondary IDs NCI-2019-01158, 2018-689-US001
- Clinicaltrials.gov ID NCT03786926