HMPL-760 in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

A Multicenter, Open-label, Phase I Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of HMPL-760 in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

A Multicenter, Open-label, Phase I Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of HMPL-760 in Patients with Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HMPL-760 administered orally in subjects with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). Patients with relapsed/refractory B-NHL, including chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular cell lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and lymphoplasmacytic/macroglobulinemia (LPL/WM).

Inclusion Criteria:

1. Signed Informed Consent Form (ICF)

2. Age ≥18 years

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In the expansion stage, ECOG performance status 0-2

4. Relapsed/refractory patients with histologically confirmed lymphoma

   • CLL confirmed by cytology (flow cytometry)
   • LPL/WM diagnosed by relevant tests including serum, bone marrow, and pathological examinations.

5. Except for CLL and WM, at least one bidimensionally measurable lesion is required by CT scan, which means the largest diameter of lymph node lesions >1.5 cm or extranodal lesions >1.0 cm; For lesions that cannot be well displayed by CT due to anatomical location (such as limb or soft tissue lesions), MRI measurement can be used.

6. Expected survival longer than 24 weeks

Exclusion Criteria:

Patients who met any of the following criteria are excluded from the study:

1. Lymphoma patients with central nervous system (CNS) or leptomeningeal invasion
2. Inadequate organ function of liver and kidney
3. Carcinoma in situ of the breast History of liver disease, including cirrhosis, alcoholism, or currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
4. Any anti-tumor therapy including chemotherapy and radiotherapy within 3 weeks prior to the first dose of study drug
5. Within 7 days or approximately 5 half-lives (whichever is longer) prior to the first dose of the investigational drug, received any corticosteroids or approved small molecule targeted anti-cancer therapies.
6. Any monoclonal antibody used for anti-tumor therapy within 4 weeks or 2 half-lives prior to the first dose of study drug, whichever is longer
7. Prior use of any anti-tumor vaccine
8. Prior administration of radioimmunotherapy within 3 months prior to the first dose of study drug
9. Any uncontrolled active infection
10. History of drug-induced interstitial pneumonia