HDM2005 Combination Therapy in Relapsed/Refractory Mantle Cell Lymphoma

Inclusion Criteria:

1. Adult participants aged 18 years or older.
2. Histologically confirmed mantle cell lymphoma with cyclin D1 overexpression or documented t(11;14).
3. 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.
4. At least one measurable lesion according to the 2014 Lugano response criteria.
5. Eastern Cooperative Oncology Group performance status of 0 to 1 for the Phase Ib part, or 0 to 2 for the Phase III part.
6. Adequate organ and bone marrow function as defined in the protocol.
7. Estimated life expectancy of more than 3 months.
8. Willingness to provide archived or fresh tumor tissue for central pathology review, if available.
9. Willingness to follow the study treatment plan, visit schedule, and contraceptive requirements.
10. Written informed consent provided before any study-specific procedures.

Exclusion Criteria:

1. Leukemic non-nodal mantle cell lymphoma.
2. Known central nervous system involvement by lymphoma.
3. Prior treatment with a ROR1-targeted therapy.
4. Active or uncontrolled infection requiring systemic treatment.
5. Active infectious disease, including uncontrolled hepatitis B, active hepatitis C, human immunodeficiency virus infection, or active syphilis, as defined in the protocol.
6. History or current evidence of interstitial lung disease, active interstitial lung disease, or radiation pneumonitis requiring steroid treatment.
7. Clinically significant cardiovascular or cerebrovascular disease that may increase study risk.
8. 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.
9. Prior solid organ transplantation.
10. Other active malignancy or malignancy with a clinically significant risk of recurrence, except for certain adequately treated cancers as defined in the protocol.
11. Unresolved clinically significant toxicity from prior anti-cancer therapy.
12. Recent anti-cancer therapy, investigational treatment, major surgery, or radiotherapy within the protocol-defined washout period.
13. Known allergy or contraindication to any study treatment or its components.
14. Active autoimmune disease or immunodeficiency requiring systemic treatment, except for protocol-defined stable conditions.
15. Pregnancy, breastfeeding, or planned pregnancy during the study.
16. Any medical, psychiatric, laboratory, or social condition that, in the investigator's judgment, may interfere with study participation, study assessments, or participant safety.