Diffuse Large B Cell Lymphoma (DLBCL)
Conditions
Keywords
DLBCL
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.
Interventions
DRUGHDM2005
HDM2005 will be administered as an intravenous injection.
Rituximab or Rituximab biosimilar will be administered as an intravenous injection.
DRUGGemcitabine
Gemcitabine will be administered as an intravenous injection.
DRUGOxaliplatin
Oxaliplatin will be administered as an intravenous injection.
DRUGCyclophosphamide
Cyclophosphamide will be administered as an intravenous injection.
DRUGDoxorubicin
Doxorubicin will be administered as an intravenous injection.
DRUGPrednisone
Prednisone will be administered orally.
Sponsors
Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RP2D of HDM2005 | Up to ~30 months | Recommended phase 2 dose of HDM2005 in combination with SoC in patients with r/r DLBCL and untreated DLBCL |
| Number of participants who experience dose-limiting toxicities (DLTs) in dose-escalation part | Up to ~3 weeks | 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 | Up to ~54 months | 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 | Up to ~30 months | CR rate is defined as the percentage of participants who achieve a complete response (CR) per Lugano criteria, as determined by the investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to ~54 months | PFS is defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression/relapse or death from any cause, whichever occurs first as determined by the investigator |
| Duration of response (DOR) | Up to ~54 months | DOR is defined as the interval from the first documentation of CR or PR until disease progression or death due to any cause, whichever occurs first |
| Plasma concentration of HDM2005, total antibody and monomethyl auristatin E (MMAE) | Up to ~30 months | Plasma concentration of HDM2005, total antibody and MMAE will be reported for each dose level |
| Time to progression (TTP) | Up to ~54 months | TTP is defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression as determined by the investigator |
| Overall survival (OS) | Up to ~54 months | OS is defined as the time from randomization to death due to any cause |
| Time to response (TTR) | Up to ~54 months | TTR is defined as the interval from the start of study therapy to the first documentation of CR or PR |
| Number of participants positive for anti-drug antibodies (ADA) | Up to ~30 months | 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 | Up to ~54 months | 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) | Up to ~30 months | 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 |
Countries
China
Contacts
Primary ContactMeiping Kong
Outcome results
None listed