A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)

Официальное название

A Phase 2/3 Multicenter, Open-label, Randomized, Active-Control Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-003)

Обзор

The purpose of this Phase 2/3, randomized, multisite, open-label, dose confirmation, and expansion study is to evaluate the safety, and efficacy of zilovertamab vedotin (ZV) in combination with standard of care options for the treatment of rrDLBCL. This study will be divided into 2 parts: Dose Confirmation (Part 1) and Efficacy Expansion (Part 2) and will enroll participants who are at least 18 years of age with rrDLBCL. The hypotheses are: ZV in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx) is superior to R-GemOx with respect to progression-free survival (PFS) per Lugano response criteria by blinded independent review committee (BICR); and that ZV in combination with bendamustine rituximab (BR) is superior to BR with respect to PFS per Lugano response criteria by BICR. With protocol amendment 4 (effective: 04-April-2024), enrollment in Cohort B (study arms Bendamustine Rituximab \[BR\] and ZV + BR) is discontinued. No efficacy outcome analysis and hypothesis testing will be conducted for Cohort B.

Вмешательства

• Биопрепарат Zilovertamab vedotin
  Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg
• Биопрепарат Rituximab
  IV Infusion 375 mg/m\^2
• Препарат Gemcitabine
  IV Infusion 1000 mg/m\^2
• Препарат Oxaliplatin
  IV Infusion 100 mg/m\^2
• Препарат Bendamustine
  IV Infusion 90 mg/m\^2
• Препарат Granulocyte Colony-Stimulating Factor (G-CSF)
  Prophylactic G-CSF will be administered at each cycle of zilovertamab vedotin as per the institutional guidelines.

Первичные конечные точки

• Number of participants who experienced dose-limiting toxicities (DLTs) in Part 1 [Срок оценки: Up to ~6 weeks]
• Number of participants who experienced an adverse event (AE) [Срок оценки: Up to ~68 months]
• Number of participants who discontinued study treatment due to an AE [Срок оценки: Up to ~68 months]
• Overall survival (OS) [Срок оценки: Up to ~35 months]
• Progression-free survival (PFS) [Срок оценки: Up to ~35 months]

Вторичные конечные точки (2)

• Objective response rate (ORR) [Срок оценки: Up to ~35 months]
• Duration of response (DOR) [Срок оценки: Up to ~35 months]

Критерии участия

Критерии включения

• Has a histologically confirmed diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL).
• Has radiographically measurable DLBCL per the Lugano Response Criteria, as assessed locally by the investigator.
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 within 7 days prior to study treatment initiation.
• Has adequate organ function.
• Is able to provide new or archival tumor tissue sample not previously irradiated.

Zilovertamab vedotin plus R-GemOx, or R-GemOx study arms:

• Has relapsed or refractory DLBCL and is ineligible for or have failed autologous stem-cell transplant (ASCT) and have failed at least 1 line of prior therapy.
• Has post-chimeric antigen receptor T (post-CAR-T) cell therapy failure or is ineligible for CAR-T cell therapy.

Not applicable with protocol amendment 4: Zilovertamab vedotin plus Bendamustine Rituximab (BR), and Bendamustine Rituximab study arms:

• Has relapsed or refractory DLBCL and is ineligible for or have failed ASCT and have failed at least 2 lines of prior therapy.
• Has post-CAR-T therapy failure or is ineligible for CAR-T cell therapy.

Критерии исключения

• Not applicable with protocol amendment 4: Has history of transformation of indolent disease to DLBCL
• Has received solid organ transplant at any time.
• Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL).
• Has clinically significant (ie, active) cardiovascular disease or serious cardiac arrhythmia requiring medication.
• Has ongoing graft-versus-host disease (GVHD) of any grade, or is receiving treatment for their GVHD.
• Has clinically significant pericardial or pleural effusion.
• Has ongoing Grade >1 peripheral neuropathy.
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
• Has a demyelinating form of Charcot-Marie-Tooth disease.
• Has contraindication to any of the study intervention components including but not limited to prior anaphylactic reaction.
• Has received prior systemic anticancer therapy, including investigational agents within 4 weeks prior to the first dose of study intervention.
• Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Has ongoing corticosteroid therapy.
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
• Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma. Participants with prior CNS involvement are eligible if their CNS disease is in radiographic, cytological (for cerebrospinal fluid disease), and clinical remission.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known active Hepatitis C virus infection.
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 26 центров

• Palo Verde Hematology/ Oncology Center, Ltd. ( Site 0175) — Glendale
• Beverly Hills Cancer Center ( Site 0184) — Beverly Hills
• Bass Medical Group ( Site 0166) — Walnut Creek
• Innovative Clinical Research Institute ( Site 0122) — Whittier
• Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0163) — Boca Raton
• Clermont Oncology Center ( Site 0174) — Clermont
• BRP-Hialeah Hospital ( Site 0182) — Hialeah
• Illinois Cancer Specialists ( Site 8000) — Niles
• … и ещё 18 центров

Китай · 16 центров

• Beijing Cancer hospital ( Site 3000) — Пекин
• Chongqing University Cancer Hospital-Medical Oncology ( Site 3025) — Чунцин
• Chongqing University Three Gorges Hospital ( Site 3026) — Чунцин
• Sun Yat-sen University Cancer Center-Internal Medicine ( Site 3001) — Гуанчжоу
• Zhujiang Hospital ( Site 3002) — Гуанчжоу
• The First Affiliated Hospital of Henan University of Science &Technology ( Site 3029) — Luoyang
• Henan Cancer Hospital-hematology department ( Site 3013) — Чжэнчжоу
• Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site — Ухань
• … и ещё 8 центров

Япония · 13 центров

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Польша · 8 центров

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Чили · 7 центров

• Biocenter ( Site 2401) — Concepción
• IC La Serena Research ( Site 2405) — La Serena
• Oncocentro Valdivia ( Site 2407) — Valdivia
• FALP-UIDO ( Site 2400) — Santiago
• Clínica Inmunocel ( Site 2404) — Santiago
• Clínica RedSalud Vitacura ( Site 2409) — Santiago
• Bradfordhill ( Site 2403) — Santiago

Turkey (Türkiye) · 6 центров

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Аргентина · 5 центров

• Hospital Italiano de Buenos Aires ( Site 2203) — Ciudad Autonoma de Buenos Aires
• Instituto de Investigaciones Clínicas Mar del Plata ( Site 2205) — Mar del Plata
• Hospital Aleman ( Site 2200) — Buenos Aites
• Hospital Privado Universitario de Córdoba ( Site 2202) — Córdoba
• Instituto Alexander Fleming ( Site 2201) — CABA

Колумбия · 5 центров

• Hospital Pablo Tobon Uribe ( Site 0804) — Medellín
• FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO AN — Bogotá
• Instituto Médico de Alta Tecnologia S.A.S ( Site 0803) — Montería
• Oncologos del Occidente ( Site 0800) — Pereira
• Fundacion Valle del Lili ( Site 0802) — Cali

Перу · 5 центров

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Украина · 5 центров

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Италия · 4 центра

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Австралия · 3 центра

• Townsville University Hospital ( Site 1800) — Townsville
• Grampians Health ( Site 1802) — Ballarat
• Royal Perth Hospital-Haematology ( Site 1801) — Perth

Бразилия · 3 центра

• Hospital Erasto Gaertner ( Site 2302) — Curitiba
• Liga Norte Riograndense Contra o Câncer ( Site 2305) — Natal
• Hospital Paulistano ( Site 2300) — São Paulo

Греция · 3 центра

• Evangelismos General Hospital of Athens ( Site 0900) — Athens
• Regional General Hospital of Athens "Laiko" ( Site 0901) — Athens
• University Hospital of Alexandroupolis ( Site 0903) — Alexandroupoli

Guatemala · 3 центра

• MEDI-K ( Site 2602) — Guatemala City
• Private Practice- Dr. Rixci Augusto Lenin Ramírez ( Site 2601) — Guatemala City
• CELAN,S.A ( Site 2603) — Guatemala City

Израиль · 3 центра

• Emek Medical Center-Hematology Unit ( Site 1102) — Afula
• … и ещё 2 центра

Мексика · 3 центра

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Таиланд · 3 центра

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Великобритания · 3 центра

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Costa Rica · 2 центра

• Hospital Metropolitano - Sede Lindora ( Site 2500) — Santa Ana
• CIMCA ( Site 2501) — San José

Франция · 2 центра

• centre hospitalier lyon sud-Service Hématologie ( Site 0702) — Pierre-Bénite
• Pitie Salpetriere University Hospital-Clinical haematology ( Site 0700) — Paris

Гонконг · 2 центра

• Queen Mary Hospital ( Site 3100) — Гонконг
• Princess Margaret Hospital ( Site 3101) — Гонконг

South Korea · 2 центра

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Канада · 1 центр

• Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0200) — Toronto

Дания · 1 центр

• Aarhus Universitetshospital, Skejby ( Site 1701) — Aarhus

Новая Зеландия · 1 центр

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Идентификаторы

NCT: NCT05139017 · 2140-003 · VLS-101 · MK-2140-003 · waveLINE-003 · 2022-502646-27-00 · U1111-1285-0898 · jRCT2011250068

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗