HDM2005 Combination Therapy in Relapsed/Refractory Mantle Cell Lymphoma

NCT07697339 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: HDM2005-301
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase Ib/III, multicenter, open-label clinical study of HDM2005 in combination with rituximab and lenalidomide in adult patients with relapsed or refractory mantle cell lymphoma. Mantle cell lymphoma is a type of non-Hodgkin lymphoma. Some patients have disease that comes back after treatment or does not respond well to available treatments. This study is designed to evaluate whether adding HDM2005 to rituximab and lenalidomide may provide clinical benefit for patients with relapsed or refractory mantle cell lymphoma who have previously received an anti-CD20 antibody-containing regimen and at least one Bruton's tyrosine kinase inhibitor. The study includes two parts. In the Phase Ib part, participants will receive HDM2005 in combination with rituximab and lenalidomide. The main goals of this part are to evaluate the safety and tolerability of the combination, assess preliminary anti-tumor activity, and determine the recommended dose of HDM2005 for the Phase III part. In the Phase III part, eligible participants will be randomly assigned to receive either HDM2005 at the recommended Phase III dose in combination with rituximab and lenalidomide, or the investigator's choice of comparator treatment with rituximab plus lenalidomide or bendamustine plus rituximab. The main goals of the Phase III part are to compare the anti-tumor activity and clinical benefit of the HDM2005 combination with the comparator treatments. The main measures of efficacy include objective response rate and progression-free survival, assessed according to the 2014 Lugano response criteria. The study will also evaluate safety, pharmacokinetics, immunogenicity, overall survival, duration of response, and other measures of anti-tumor activity.

Conditions

Mantle Cell Lymphoma

Keywords

ROR1-ADC; Mantle cell lymphoma

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Incidence and severity of adverse events

  Incidence and severity of adverse events, serious adverse events, and adverse events of special interest will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Dose interruptions, dose modifications, laboratory test results, vital signs, and other safety assessments will also be evaluated.

  From the date of first dose until end of treatment, assessed up to 12 months.

• Phase Ib: Objective response rate assessed by investigator

  Objective response rate is defined as the proportion of participants who achieve complete response or partial response as assessed by the investigator according to the 2014 Lugano response criteria.

  From the first dose of study treatment until disease progression, or other protocol re-specified reasesons, whichever occurs first, assessed up to 11 months.

Study Arms (4)

Phase Ib Cohort 1: HDM2005 1.2 mg/kg + R-Len

EXPERIMENTAL

Participants in this Phase Ib cohort will receive HDM2005 1.2 mg/kg in combination with rituximab and lenalidomide during induction treatment.

Drug: Phase Ib Cohort 1: HDM2005 1.2 mg/kg + R-Len

Phase Ib Cohort 2: HDM2005 1.4 mg/kg + R-Len

EXPERIMENTAL

Participants in this Phase Ib cohort will receive HDM2005 1.4 mg/kg in combination with rituximab and lenalidomide during induction treatment.

Drug: Phase Ib Cohort 2: HDM2005 1.4 mg/kg + R-Len

Phase III Active Arm: HDM2005 plus rituximab and lenalidomide

EXPERIMENTAL

HDM2005 will be administered in combination with rituximab and lenalidomide.

Drug: HDM2005 plus rituximab and lenalidomide

Phase III Control Arm: Rituximab plus lenalidomide

ACTIVE COMPARATOR

Rituximab plus lenalidomide is used as part of the HDM2005 combination regimen as control arm.

Drug: Rituximab plus lenalidomide

Interventions

Phase Ib Cohort 1: HDM2005 1.2 mg/kg + R-Len DRUG

HDM2005 will be administered in combination with rituximab and lenalidomide.

Also known as: HDM2005 + R-Len

Phase Ib Cohort 1: HDM2005 1.2 mg/kg + R-Len

Rituximab plus lenalidomide DRUG

Rituximab plus lenalidomide is used as part of the HDM2005 combination regimen and may also be selected as comparator treatment in the Phase III part.

Also known as: R-Len

Phase III Control Arm: Rituximab plus lenalidomide

Phase Ib Cohort 2: HDM2005 1.4 mg/kg + R-Len DRUG

HDM2005 will be administered in combination with rituximab and lenalidomide.

Also known as: HDM2005 + R-Len

Phase Ib Cohort 2: HDM2005 1.4 mg/kg + R-Len

HDM2005 plus rituximab and lenalidomide DRUG

HDM2005 will be administered in combination with rituximab and lenalidomide.

Also known as: HDM2005 + R-Len

Phase III Active Arm: HDM2005 plus rituximab and lenalidomide

Eligibility Criteria

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

You may qualify if:

• Adult participants aged 18 years or older.
• Histologically confirmed mantle cell lymphoma with cyclin D1 overexpression or documented t(11;14).
• Relapsed or refractory mantle cell lymphoma after prior treatment with an anti-CD20 antibody-containing regimen and at least one Bruton's tyrosine kinase inhibitor, unless a BTK inhibitor was not suitable or was not tolerated.
• At least one measurable lesion according to the 2014 Lugano response criteria.
• Eastern Cooperative Oncology Group performance status of 0 to 1 for the Phase Ib part, or 0 to 2 for the Phase III part.
• Adequate organ and bone marrow function as defined in the protocol.
• Estimated life expectancy of more than 3 months.
• Willingness to provide archived or fresh tumor tissue for central pathology review, if available.
• Willingness to follow the study treatment plan, visit schedule, and contraceptive requirements.
• Written informed consent provided before any study-specific procedures.

You may not qualify if:

• Leukemic non-nodal mantle cell lymphoma.
• Known central nervous system involvement by lymphoma.
• Prior treatment with a ROR1-targeted therapy.
• Active or uncontrolled infection requiring systemic treatment.
• Active infectious disease, including uncontrolled hepatitis B, active hepatitis C, human immunodeficiency virus infection, or active syphilis, as defined in the protocol.
• History or current evidence of interstitial lung disease, active interstitial lung disease, or radiation pneumonitis requiring steroid treatment.
• Clinically significant cardiovascular or cerebrovascular disease that may increase study risk.
• Prior allogeneic hematopoietic stem cell transplantation with active or clinically significant graft-versus-host disease, or need for systemic immunosuppressive treatment for graft-versus-host disease.
• Prior solid organ transplantation.
• Other active malignancy or malignancy with a clinically significant risk of recurrence, except for certain adequately treated cancers as defined in the protocol.
• Unresolved clinically significant toxicity from prior anti-cancer therapy.
• Recent anti-cancer therapy, investigational treatment, major surgery, or radiotherapy within the protocol-defined washout period.
• Known allergy or contraindication to any study treatment or its components.
• Active autoimmune disease or immunodeficiency requiring systemic treatment, except for protocol-defined stable conditions.
• Pregnancy, breastfeeding, or planned pregnancy during the study.

Sponsors & Collaborators

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

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Rituximab; Lenalidomide

Condition Hierarchy (Ancestors)

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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Ruichao Zeng, PhD

CONTACT

+86-571-89903388; zengruichao@eastchinapharm.com

Study Design

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

Study Record Dates

• First Submitted: July 2, 2026
• First Posted: July 13, 2026
• Study Start: July 10, 2026
• Primary Completion (Estimated): August 10, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 13, 2026

Record last verified: 2026-07