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

A Phase 1b/2 Study to Evaluate the Safety, Tolerability, and Antitumor Activity of HDM2005 in Combination With Standard of Care in Patients With Diffuse Large B-Cell Lymphoma

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.

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.