HDM2005 combined with standard treatment for 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

We are testing whether adding HDM2005 to standard chemotherapy helps adults with diffuse large B‑cell lymphoma who are either newly diagnosed or whose disease has returned.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 97 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 21 sites (Beijing, Beijing Municipality and 20 other locations)
• Trial ID: NCT07124936 on ClinicalTrials.gov

What this trial studies

This is a Phase 1b/2, open-label study that gives HDM2005 together with established rituximab-based chemotherapy regimens and follows a dose-escalation phase followed by a dose-expansion phase. Cohort A enrolls patients with relapsed or refractory DLBCL and receives HDM2005 plus R‑GemOx, while Cohort B enrolls untreated patients (IPI 2–5) and receives HDM2005 plus R‑CHP. Key endpoints include safety, tolerability, and antitumor activity, with eligibility requiring measurable disease and adequate organ function. The study is conducted at three cancer centers in China and monitors patients for adverse events and tumor response during and after treatment.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 years with histologically confirmed DLBCL, ECOG 0–1, measurable disease and adequate organ function, with Cohort A having had at least one prior systemic therapy and Cohort B having received no prior DLBCL treatment and an IPI score of 2–5.

Not a fit: Patients with active CNS lymphoma, prior allogeneic stem cell transplant with ongoing or acute GVHD, recent progressing/treated additional malignancy, significant organ dysfunction, or ECOG performance status >1 are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, adding HDM2005 could increase response rates or lengthen remissions when combined with standard DLBCL regimens.

How similar studies have performed: Other trials combining novel targeted agents with rituximab-based regimens have shown mixed results, and HDM2005 appears to be a novel agent with limited published clinical data to date.

Eligibility criteria

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.

Where this trial is running

Beijing, Beijing Municipality and 20 other locations

• Peking University Cancer Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (Not_yet_recruiting)
• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Not_yet_recruiting)
• The Affiliated Tumor Hospital of Guangxi Medical University — Nanning, Guangxi, China (Not_yet_recruiting)
• Affiliated Tumor Hospital of Harbin Medical University — Harbin, Heilongjiang, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Not_yet_recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Not_yet_recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Not_yet_recruiting)
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Not_yet_recruiting)
• HunanCancer Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• Second Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Not_yet_recruiting)
• The First Affiliated Hospital Of Nanchang University — Nanchang, Jiangxi, China (Not_yet_recruiting)
• The first hospital of Jilin University — Changchun, Jilin, China (Not_yet_recruiting)
• Shengjing Hospital Affiliated to China Medical University — Shenyang, Liaoning, China (Not_yet_recruiting)
• The First Affiliated Hospital of Xi'an Jiaotong University — Xi'an, Shaanxi, China (Not_yet_recruiting)
• Cancer Hospital of Shandong First Medical University (Shandong Cancer Institute,Shandong Cancer Hospital) — Jinan, Shandong, China (Not_yet_recruiting)
• Shanxi Cancer Hospital — Taiyuan, Shanxi, China (Not_yet_recruiting)
• West China Hospital，Sichuan University — Chengdu, Sichuan, China (Not_yet_recruiting)
• The Second Affiliated Hospital of Kunming Medical UniversityThe Second Affiliated Hospital of Kunming Medical University — Kunming, Yunnan, China (Active_not_recruiting)
• Yunnan Cancer Hospital — Kunming, Yunnan, China (Not_yet_recruiting)
• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Meiping Kong

Conditions Diffuse Large B Cell Lymphoma; DLBCL