A Study of HDM2005 in Combination With Standard of Care in Patients With Diffuse Large B-Cell Lymphoma

Официальное название

A Phase 1b/2 Study to Evaluate the Safety, Tolerability, and Antitumor Activity of HDM2005 in Combination With Standard of Care in Patients With Diffuse Large B-Cell Lymphoma

Обзор

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.

Вмешательства

• Препарат HDM2005
  HDM2005 will be administered as an intravenous injection.
• Препарат Rituximab or Rituximab biosimilar
  Rituximab or Rituximab biosimilar will be administered as an intravenous injection.
• Препарат Gemcitabine
  Gemcitabine will be administered as an intravenous injection.
• Препарат Oxaliplatin
  Oxaliplatin will be administered as an intravenous injection.
• Препарат Cyclophosphamide
  Cyclophosphamide will be administered as an intravenous injection.
• Препарат Doxorubicin
  Doxorubicin will be administered as an intravenous injection.
• Препарат Prednisone
  Prednisone will be administered orally.

Первичные конечные точки

• Number of participants who experience dose-limiting toxicities (DLTs) in dose-escalation part [Срок оценки: Up to ~3 weeks]
• Number of participants who experience adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) in dose-escalation part [Срок оценки: Up to ~54 months]
• Complete response (CR) rate in dose-expansion part [Срок оценки: Up to ~30 months]
• RP2D of HDM2005 [Срок оценки: Up to ~30 months]

Вторичные конечные точки (9)

• Plasma concentration of HDM2005, total antibody and monomethyl auristatin E (MMAE) [Срок оценки: Up to ~30 months]
• Number of participants positive for anti-drug antibodies (ADA) [Срок оценки: Up to ~30 months]
• Number of participants who experience adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) in dose-expansion part [Срок оценки: Up to ~54 months]
• Objective response rate (ORR) [Срок оценки: Up to ~30 months]
• Progression-free survival (PFS) [Срок оценки: Up to ~54 months]
• Duration of response (DOR) [Срок оценки: Up to ~54 months]
• Time to response (TTR) [Срок оценки: Up to ~54 months]
• Time to progression (TTP) [Срок оценки: Up to ~54 months]
• Overall survival (OS) [Срок оценки: Up to ~54 months]

Критерии участия

Критерии включения

• 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.
• 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.
• Adequate organ system and hematologic function as defined in protocol.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 21 центр

• Peking University Cancer Hospital — Пекин
• Fujian Cancer Hospital — Фучжоу
• Sun Yat-sen University Cancer Center — Гуанчжоу
• The Affiliated Tumor Hospital of Guangxi Medical University — Nanning
• Affiliated Tumor Hospital of Harbin Medical University — Харбин
• The First Affiliated Hospital of Zhengzhou University — Чжэнчжоу
• Henan Cancer Hospital — Чжэнчжоу
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Ухань
• … и ещё 13 центров

Идентификаторы

NCT: NCT07124936 · HDM2005-104

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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