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.
Male or female aged 18-75 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Life expectancy >12 weeks.
Histologically confirmed diffuse large B-cell lymphoma (DLBCL).
Known active central nervous system (CNS) lymphoma.
Prior of allogeneic hematopoietic stem cell transplantation and has acute or ongoing graft-versus-host disease (GVHD) of any grade.
Known additional malignancy that is progressing or has required active treatment within the past 3 years.
History of severe bleeding disorders.
Single group
HDM2005
DrugHDM2005 will be administered as an intravenous injection.
Rituximab or Rituximab biosimilar
DrugRituximab or Rituximab biosimilar will be administered as an intravenous injection.
Gemcitabine
DrugGemcitabine will be administered as an intravenous injection.
Oxaliplatin
DrugOxaliplatin will be administered as an intravenous injection.
Cyclophosphamide
DrugCyclophosphamide will be administered as an intravenous injection.
Doxorubicin
DrugDoxorubicin will be administered as an intravenous injection.
Prednisone
DrugPrednisone will be administered orally.
Number of participants who experience dose-limiting toxicities (DLTs) in dose-escalation part
The CTCAE, Version 5.0 will be used to grade the severity of AEs in this study. DLTs will be reported for dose-escalation part of this study.
Number of participants who experience adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) in dose-escalation part
Incidence and grading of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) (based on the National Cancer Institute's Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0). Incidence of treatment interruption and dose adjustment due to AEs and changes in laboratory tests, vital signs, physical examination, electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status score.
Complete response (CR) rate in dose-expansion part
CR rate is defined as the percentage of participants who achieve a complete response (CR) per Lugano criteria, as determined by the investigator
RP2D of HDM2005
Recommended phase 2 dose of HDM2005 in combination with SoC in patients with r/r DLBCL and untreated DLBCL
Plasma concentration of HDM2005, total antibody and monomethyl auristatin E (MMAE)
Plasma concentration of HDM2005, total antibody and MMAE will be reported for each dose level
Number of participants positive for anti-drug antibodies (ADA)
Number of participants with positive ADA will be assessed
Number of participants who experience adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) in dose-expansion part
Incidence and grading of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) (based on the National Cancer Institute's Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0). Incidence of treatment interruption and dose adjustment due to AEs and changes in laboratory tests, vital signs, physical examination, electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status score.
Objective response rate (ORR)
ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano criteria as determined by the investigator
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