A Study of HDM2005 in Combination With Standard of Care in Patients With Diffuse Large B-Cell Lymphoma

Hangzhou Zhongmei Huadong Pharmaceutical

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Diffuse Large B Cell Lymphoma (DLBCL)

Treatments: Drug: Gemcitabine; Drug: Rituximab or Rituximab biosimilar; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: HDM2005; Drug: Prednisone; Drug: Oxaliplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT07124936

HDM2005-104

Details and patient eligibility

About

The purpose of this phase 1b/2 study is to evaluate the safety, tolerability, and antitumor activity of HDM2005 in combination with standard of care in participants with diffuse large B-cell lymphoma. This study will include two arms: Cohort A (HDM2005 + R-GemOx) will enroll participants with relapsed/refractory DLBCL. Cohort B (HDM2005 + R-CHP) will enroll participants with untreated DLBCL. The study will consist of two parts: dose-escalation part and dose-expansion part.

Enrollment: 97 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female aged 18-75 years.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

3. Life expectancy >12 weeks.

4. Histologically confirmed diffuse large B-cell lymphoma (DLBCL).

   a. Cohort B: International Prognostic Index (IPI) score of 2-5.

5. Prior treatment:

   1. Cohort A: At least one (≥1) line of prior systemic therapy.
   2. Cohort B: Has received no prior treatment for DLBCL.

6. At least one bi-dimensionally measurable (≥1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥1 cm) extranodal lesion, as measured on computed tomography (CT) scan.

7. Adequate organ system and hematologic function as defined in protocol.

Exclusion criteria

1. Known active central nervous system (CNS) lymphoma.
2. Prior of allogeneic hematopoietic stem cell transplantation and has acute or ongoing graft-versus-host disease (GVHD) of any grade.
3. Known additional malignancy that is progressing or has required active treatment within the past 3 years.
4. History of severe bleeding disorders.
5. History of interstitial lung disease or radiation pneumonitis.
6. Prior solid organ transplant.
7. Ongoing Grade >1 treatment-related adverse events.
8. Current or history of clinically significant cardiovascular and cerebrovascular diseases.
9. Active infection requiring systemic therapy.
10. Concurrent active HBV or HCV infection or known history of human immunodeficiency virus (HIV) infection.
11. Prior ROR1-targeted therapy.
12. Ongoing corticosteroid therapy.
13. Current active autoimmune disease or history of autoimmune disease requiring treatment.
14. History of drug anaphylaxis or severe food allergy.
15. Any history or current evidence of disease, treatment, or laboratory abnormality as determined by the investigator that may affect the study results, interfere with the subject's full participation in the study, or be contrary to the subject's best interests.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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97 participants in 2 patient groups

Participants with r/r DLBCL (Cohort A)

Experimental group

Description:

Participants with r/r DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6-8) plus 1000 mg/ m\^2 gemcitabine (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6-8), 100 mg/ m\^2 oxaliplatin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 6-8 cycles.

Treatment:

Drug: Oxaliplatin

Drug: HDM2005

Drug: Gemcitabine

Drug: Rituximab or Rituximab biosimilar

Participants with untreated DLBCL (Cohort B)

Experimental group

Description:

Participants with untreated DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6) plus 750 mg/m\^2 cyclophosphamide (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), 50 mg/m\^2 doxorubicin (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 and 2 Cycle 1 and Day 1 Cycle 2 to 6 of each 3-week cycle for up to 6 cycles. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles.

Treatment:

Drug: Prednisone

Drug: HDM2005

Drug: Doxorubicin

Drug: Cyclophosphamide

Drug: Rituximab or Rituximab biosimilar