A Phase I, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523 in Patients With Relapsed or Refractory Lymphoma

2018-523-00US1

This is a Phase I, open-label, multicenter study of HMPL-523 administered orally to patients with relapsed or refractory lymphoma who have exhausted approved therapy options. This study consists of a dose escalation stage (Stage1) and a dose expansion stage (Stage 2).

2019-09-26

2024-12-01

2026-01-01

Active (not recruiting)

Early phase I

140

Inclusion Criteria: Patients must meet the following criteria to be eligible for study entry: 1. Signed informed consent form (ICF). 2. Age ≥18 years. 3. ECOG performance status of 0 or 1. 4. Histologically confirmed lymphoma, including Hodgkin's lymphoma and non-Hodgkin's lymphoma. In the dose expansion stage, the tumor types may be restricted to any or all of the following tumor types. There may be approximately 10 patients in each cohort depending on response signals suggesting efficacy, except for 2 identified cohorts with approximately 20 patients per cohort: relapsed or refractory CLL/SLL, CLL/SLL post-BTK exposure (n=20), MCL, FL (Grade 1-3a) (n=20), MZL, WM/LPL, PTCL,CBCL, and/or HL 5. Patients with relapsed or refractory lymphoma who have exhausted all approved therapy options. 6. In the dose expansion stage, patients must have measurable disease for an objective response assessment, except for patients with CLL and WM/LPL 7. Availability of tumor sample for patients in dose expansion cohorts: This may be an archival tissue sample obtained after most recent therapy or a fresh biopsy; if tumor sample is not available, the Sponsor may waive the requirement after discussion 8. Expected survival of more than 24 weeks as determined by the investigator. 9. Male patients must agree to use a condom and female patients of childbearing potential must agree to use highly effective contraceptive measures for 30 days after the last dose of study drug. These include as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, and transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, and implantable), intrauterine contraceptive device, intrauterine hormone release system, bilateral tubal occlusion, or a vasectomized partner, provided that male partner is the sole sexual partner of the female patient. Postmenopausal females (women who have not had menses for at least 1 year without an alternative medical cause) are exempt from this criterion. Exclusion Criteria 1. Patients with 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), aspartate aminotransferase and/or alanine aminotransferase \>2.5 × ULN, Estimated Creatinine Clearance (CrCl) per Cockcroft-Gault \[Dose Escalation portion of trial (Stage 1) CrCl \< 40 mL/min, Dose Expansion portion of trial (Stage 2) CrCl \< 30 mL/min\], Serum amylase or lipase \>ULN, International normalized ratio \>1.5 × ULN, or activated partial thromboplastin time \>1.5 × ULN 4. Patients with clinically detectable second primary malignant tumors at enrollment or other malignant tumors within the last 2 years (with the exception of radically treated basal cell or squamous cell carcinoma of the skin, in situ cervix, or in situ breast cancer). 5. Any anticancer therapy, including chemotherapy, hormonal therapy, biologic therapy, vaccine, or radiotherapy within 3 weeks prior to the initiation of study treatment. 6. Herbal therapy within 1 week prior to the initiation of study treatment. 7. Prior use of any anti-cancer vaccine 8. Prior treatment with any spleen tyrosine kinase (SYK) inhibitors (eg, fostamatinib) 9. Prior administration of radioimmunotherapy within 3 months before initiation of study treatment. 10. Use of strong cytochrome P450 isoform 3A inhibitors and inducers and drugs metabolized by cytochrome P450 isoform 3A, cytochrome P450 isoform 2B6, and cytochrome P450 isoform 1A2, and are identified as narrow therapeutic drugs within 7 days or 3 half-lives, whichever is longer, prior to initiation of study treatment 11. Adverse events from prior anticancer therapy that have not resolved to Grade ≤1, except for alopecia. 12. Prior autologous stem cell transplant within 6 months prior to the initiation of study treatment. 13. Prior allogeneic stem cell transplant within 6 months prior to the initiation of study treatment or with any evidence of active graft versus host disease or requirement for immunosuppressants within 28 days prior to the initiation of study treatment. 14. Clinically significant active infection (eg, pneumonia). 15. Major surgical procedure within 4 weeks prior to the initiation of study treatment. 16. Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus. 17. Pregnant (positive serum beta human chorionic gonadotropin test) or lactating women. 18. New York Heart Association Class II or greater congestive heart failure. 19. Congenital long QT syndrome or correct QT interval using Fridericia's formula (QTcF) \>480 msec 20. Current use of medication known to cause QT prolongation or Torsades de Pointes 21. History of myocardial infarction or unstable angina within 6 months prior to the initiation of study treatment. 22. History of stroke or transient ischemic attack within 6 months prior to the initiation of study treatment. 23. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease. 24. Treatment in a clinical study within 30 days prior to the initiation of study treatment. 25. 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, may affect the interpretation of the results, or renders the patient at high risk from treatment complications.

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2024-02-09