Clinical Trial of HY004 Cell Injection in the Treatment of Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

A Multi-center, Open Label, Single-arm, Phase I/II Clinical Trial of HY004 Cell Injection in the Treatment of Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

This is a multi-center, open-label, single-arm, phase I/II trial to evaluate the safety and efficacy of HY004 treatment in Adult patients with relapsed or refractory B-cell Non-Hodgkin's Lymphoma (r/r B-NHL).

This trial is a multi-center, open label, single-arm, phase I/II trial to evaluate the safety and efficacy of HY004 in Adult(aged 18~75 years old) patients with r/r B-NHL.

The phase I part of the trial is to evaluate the safety, optimal dose of HY004, Pharmacokinetics/Pharmacodynamics(PK/PD)and preliminary efficacy in the treatment of Adult patients with r/r B-NHL. The phase II part of the trial is to evaluate the efficacy and safety of HY004 in in the treatment of Adult patients with r/r B-NHL. The study includes screening, pre-treatment (Cell Product manufacture & lymphodepletion), HY004 infusion , safety and efficacy follow-up, and survival follow-up. All subjects who have received HY004 infusion will be followed for up to 2 years.

Key Inclusion Criteria:

1. Patients who are willing to sign the informed consent form;

2. Aged 18-75 years, male or female;

3. Previously received≥2nd-line adequate therapy or hematopoietic stem cell transplantation (HSCT), and patients with CD19+/CD22+ relapsed/refractory B-NHL according to the WHO classification 2017, which are provided specifically as follows:

   1. Diffuse large B cell lymphoma (DLBCL), not otherwise specified (NOS);
   2. Primary mediastinal large B cell lymphoma (PMBCL);
   3. Grade 3b follicular lymphoma;
   4. Transformed follicular lymphoma;
   5. High grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high grade B cell lymphoma - not otherwise specified.

4. Measurable imaging lesion at screening: Intranodal lesion must have a long diameter of more than 1.5 cm, and extranodal lesion must have a long diameter of more than 1.0 cm with PET-positive disease by Lugano classification .

5. PET-positive disease BY Lugano classification

6. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function.

7. Adequate vascular access for leukapheresis procedure

8. Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy.

Key Exclusion Criteria:

1. Active Central Nervous System (CNS) involvement by malignancy.

2. Patients with existing central nervous system disease or with a history of central nervous system disease.

3. Patients receiving any of the following drugs or therapies within the specified period prior to apheresis:

   1. Alemtuzumab and Bendamustine within 6 months prior to apheresis;
   2. Cladribine within 3 months prior to apheresis;
   3. Lenalidomide within 1 mouth prior to apheresis;
   4. Lymphocytotoxic chemotherapy within 2 weeks prior to apheresis - use in more than 3 half-lives prior to apheresis is eligible;
   5. Anti-CD20 monoclonal antibody and therapeutic dose of hormones within 7 d prior to apheresis;
   6. Non-lymphocytotoxic chemotherapy within 7 d prior to apheresis - use in more than 3 half-lives prior to apheresis is eligible;
   7. Venetoclax (BCL-2 inhibitor) within 4 d prior to apheresis;
   8. Idelalisib (PI3Kδ kinase inhibitor) within 2 d prior to apheresis;
   9. DLI within 6 weeks prior to apheresis;
   10. Radiotherapy within 6 weeks prior to apheresis - progressive disease at radiotherapy site, or PET positive lesion at other non-radiotherapy site is eligible;

4. Patients previously received CAR-T cell therapy, the products that have same indication and have beenlisted in China are eligible;

5. Patients who have previously received allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 mouths.

6. Patients with acute graft-versus-host disease (GVHD) or moderate-tosevere chronic GVHD within 4 weeks before screening.

7. Active systemic autoimmune disease.

8. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti- HCV positive).

9. Patients with active infections at screening.

10. History of cardiovascular disease.

11. Pregnant or nursing women.