An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hutchison Medipharma Limited

Criteria

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 are restricted to relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma, mantel cell lymphoma, follicular lymphoma (Grade 1-3a), marginal zone lymphoma, and Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma.

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 chronic lymphocytic leukemia and Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma.

7. Expected survival of more than 24 weeks as determined by the investigator.

8. Male or female patients of child-bearing potential must agree to use double barrier contraception, condoms, sponge, foams, jellies, diaphragm or intrauterine device, contraceptives (oral or parenteral), Implanon®, injectables, or other measures to avoid pregnancy during the study and for 90 days after the last day of treatment. Post-menopausal females (>50 years old and without menses for >1 year) and women who are surgically postmenopausal 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<1.5×10^9/L, Hemoglobin <80 g/L, Platelets <75×10^9/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 < 50 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.