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

NCT07124936 | Recruiting Phase 1

• 1 other identifier: HDM2005-104
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 21

Brief Summary

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.

Conditions

Diffuse Large B Cell Lymphoma (DLBCL)

Keywords

DLBCL

Outcome Measures

Primary Outcomes (4)

• 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.

  Up to ~3 weeks

• 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.

  Up to ~54 months

• 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

  Up to ~30 months

• RP2D of HDM2005

  Recommended phase 2 dose of HDM2005 in combination with SoC in patients with r/r DLBCL and untreated DLBCL

  Up to ~30 months

Secondary Outcomes (9)

• Plasma concentration of HDM2005, total antibody and monomethyl auristatin E (MMAE)

  Up to ~30 months

• Number of participants positive for anti-drug antibodies (ADA)

  Up to ~30 months

• Number of participants who experience adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) in dose-expansion part

  Up to ~54 months

• Objective response rate (ORR)

  Up to ~30 months

• Progression-free survival (PFS)

  Up to ~54 months

Study Arms (2)

Participants with r/r DLBCL (Cohort A)

EXPERIMENTAL

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.

Drug: HDM2005; Drug: Rituximab or Rituximab biosimilar; Drug: Gemcitabine; Drug: Oxaliplatin

Participants with untreated DLBCL (Cohort B)

EXPERIMENTAL

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.

Drug: HDM2005; Drug: Rituximab or Rituximab biosimilar; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone

Interventions

HDM2005 DRUG

HDM2005 will be administered as an intravenous injection.

Participants with r/r DLBCL (Cohort A); Participants with untreated DLBCL (Cohort B)

Rituximab or Rituximab biosimilar DRUG

Rituximab or Rituximab biosimilar will be administered as an intravenous injection.

Participants with r/r DLBCL (Cohort A); Participants with untreated DLBCL (Cohort B)

Gemcitabine DRUG

Gemcitabine will be administered as an intravenous injection.

Participants with r/r DLBCL (Cohort A)

Oxaliplatin DRUG

Oxaliplatin will be administered as an intravenous injection.

Participants with r/r DLBCL (Cohort A)

Cyclophosphamide DRUG

Cyclophosphamide will be administered as an intravenous injection.

Participants with untreated DLBCL (Cohort B)

Doxorubicin DRUG

Doxorubicin will be administered as an intravenous injection.

Participants with untreated DLBCL (Cohort B)

Prednisone DRUG

Prednisone will be administered orally.

Participants with untreated DLBCL (Cohort B)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• a. Cohort B: International Prognostic Index (IPI) score of 2-5.
• Prior treatment:
• Cohort A: At least one (≥1) line of prior systemic therapy.
• Cohort B: Has received no prior treatment for DLBCL.
• 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.
• Adequate organ system and hematologic function as defined in protocol.

You may not qualify if:

• 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.
• History of interstitial lung disease or radiation pneumonitis.
• Prior solid organ transplant.
• Ongoing Grade \>1 treatment-related adverse events.
• Current or history of clinically significant cardiovascular and cerebrovascular diseases.
• Active infection requiring systemic therapy.
• Concurrent active HBV or HCV infection or known history of human immunodeficiency virus (HIV) infection.
• Prior ROR1-targeted therapy.
• Ongoing corticosteroid therapy.
• Current active autoimmune disease or history of autoimmune disease requiring treatment.
• History of drug anaphylaxis or severe food allergy.
• 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.

Sponsors & Collaborators

• Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.: lead

Study Sites (21)

Peking University Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, 350000, China

NOT YET RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510050, China

NOT YET RECRUITING

The Affiliated Tumor Hospital of Guangxi Medical University

Nanning, Guangxi, 530021, China

NOT YET RECRUITING

Affiliated Tumor Hospital of Harbin Medical University

Harbin, Heilongjiang, 150081, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450000, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

NOT YET RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

NOT YET RECRUITING

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

NOT YET RECRUITING

HunanCancer Hospital

Changsha, Hunan, 410023, China

NOT YET RECRUITING

Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215005, China

NOT YET RECRUITING

The First Affiliated Hospital Of Nanchang University

Nanchang, Jiangxi, 330000, China

NOT YET RECRUITING

The first hospital of Jilin University

Changchun, Jilin, 130021, China

NOT YET RECRUITING

Shengjing Hospital Affiliated to China Medical University

Shenyang, Liaoning, 110004, China

NOT YET RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

NOT YET RECRUITING

Cancer Hospital of Shandong First Medical University (Shandong Cancer Institute,Shandong Cancer Hospital)

Jinan, Shandong, 250117, China

NOT YET RECRUITING

Shanxi Cancer Hospital

Taiyuan, Shanxi, 030013, China

NOT YET RECRUITING

West China Hospital，Sichuan University

Chengdu, Sichuan, 610041, China

NOT YET RECRUITING

The Second Affiliated Hospital of Kunming Medical UniversityThe Second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650033, China

ACTIVE NOT RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, 650118, China

NOT YET RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Gemcitabine; Oxaliplatin; Cyclophosphamide; Doxorubicin; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Central Study Contacts

Meiping Kong

CONTACT

+8613735478976; cxykongmeiping@eastchinapharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2025
• First Posted: August 15, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): October 26, 2027
• Study Completion (Estimated): October 25, 2029
• Last Updated: August 15, 2025

Record last verified: 2025-08

Locations

CN (21)