HDM2005 Combination Therapy in Relapsed/Refractory Mantle Cell Lymphoma

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• Any medical, psychiatric, laboratory, or social condition that, in the investigator's judgment, may interfere with study participation, study assessments, or participant safety.