A Study of HDM2005 in Combination With Standard of Care in Patients With Diffuse Large B-Cell Lymphoma
- Conditions
- Diffuse Large B Cell Lymphoma (DLBCL)
- Interventions
- Drug: Rituximab or Rituximab biosimilar
- Registration Number
- NCT07124936
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 97
-
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.
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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.
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Adequate organ system and hematologic function as defined in protocol.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Participants with r/r DLBCL (Cohort A) HDM2005 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. Participants with r/r DLBCL (Cohort A) Rituximab or Rituximab biosimilar 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. Participants with r/r DLBCL (Cohort A) Gemcitabine 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. Participants with r/r DLBCL (Cohort A) Oxaliplatin 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. Participants with untreated DLBCL (Cohort B) HDM2005 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. Participants with untreated DLBCL (Cohort B) Rituximab or Rituximab biosimilar 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. Participants with untreated DLBCL (Cohort B) Cyclophosphamide 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. Participants with untreated DLBCL (Cohort B) Doxorubicin 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. Participants with untreated DLBCL (Cohort B) Prednisone 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.
- Primary Outcome Measures
Name Time Method 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
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
- Secondary Outcome Measures
Name Time Method 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 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
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
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
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
Trial Locations
- Locations (21)
Peking University Cancer Hospital
🇨🇳Beijing, Beijing, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
The Affiliated Tumor Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Affiliated Tumor Hospital of Harbin Medical University
🇨🇳Ha'erbin, Heilongjiang, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
HunanCancer Hospital
🇨🇳Changsha, Hunan, China
Scroll for more (11 remaining)Peking University Cancer Hospital🇨🇳Beijing, Beijing, China