A Study to Assess BMS-986458 Alone and in Combination With Anti-lymphoma Agents in Relapsed/Refractory Non-Hodgkin Lymphomas

Официальное название

A Phase 1/2, Multi-Center, Open-Label, Dose-Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BMS-986458, Alone and in Combination With Anti-lymphoma Agents in Participants With Relapsed/Refractory Non-Hodgkin Lymphomas (R/R NHL)

Обзор

The purpose of this study is to evaluate the safety, tolerability, drug levels, and preliminary biological and clinical activity of BMS-986458, a bifunctional cereblon-dependent ligand-directed degrader of B-cell lymphoma 6 (BCL6), as a single agent and in combination with anti-lymphoma agents in participants with relapsed/refractory non-Hodgkin Lymphoma.

Вмешательства

• Препарат BMS-986458
  Specified dose on specified days.
• Препарат Rituximab
  Specified dose on specified days.
• Препарат Glofitamab/Obinutuzumab
  Specified dose on specified days
• Препарат Mosunetuzumab
  Specified dose on specified days
• Препарат Epcoritamab
  Specified dose on specified days
• Препарат Golcadomide
  Specified dose on specified days

Первичные конечные точки

• Number of participants with adverse events (AEs) [Срок оценки: Up to 2 years and 1 month]
• Number of participants with serious adverse events (SAEs) [Срок оценки: Up to 2 years and 1 month]
• Number of participants with AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria [Срок оценки: Up to Day 28]
• Number of participants with AEs leading to death [Срок оценки: Up to 2 years and 1 month]
• Number of participants with AEs leading to discontinuation [Срок оценки: Up to 2 years and 1 month]
• Number of participants with a complete response rate (CRR) according to the Lugano response criteria for Non-Hodgkin Lymphoma by Investigator assessment [Срок оценки: Up to 2 years and 11 month]

Вторичные конечные точки (9)

• Maximum concentration (Cmax) [Срок оценки: Up to 4 months]
• Time of maximum concentration (Tmax) [Срок оценки: Up to 4 months]
• Area under the plasma concentration-time curve within a dosing interval [AUC(TAU)] [Срок оценки: Up to 4 months]
• Number of participants with a complete response rate (CRR) according to the Lugano response criteria for Non-Hodgkin Lymphoma by Investigator assessment [Срок оценки: Up to 2 years]
• Number of participants with an overall response rate (ORR) according to the Lugano response criteria for Non-Hodgkin Lymphoma by investigator assessment [Срок оценки: Up to 2 years]
• Duration of response (DOR) [Срок оценки: Up to 3 years]
• Time to response (TTR) [Срок оценки: Up to 3 years]
• Progression-free survival (PFS) [Срок оценки: Up to 3 years]
• Overall survival (OS) [Срок оценки: Up to 3 years]

Критерии участия

Критерии включения

• Participants ≥ 18 years of age with frontline or R/R NHL.
• Participant must have measurable disease (defined by at least one FDG-avid lesion for FDG-avid disease and one bi-dimensionally measurable disease on cross sectional imaging by computed tomography or magnetic resonance imaging with at least one lesion > 1.5 cm in the transverse diameter).
• Participants must accept and follow pregnancy prevention plan.

Критерии исключения

• Participants must not have an Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2.
• Participants with an inability to comply with listed restrictions, precautions and prohibited treatments.
• Participants must not have prior CAR-T, or radiotherapy ≤ 4 weeks, systemic anticancer treatment ≤ 5 half-lives or 4 weeks, allogeneic SCT ≤ 6 months (only applicable to BMS-986458 single agent or rituximab combination cohorts), or autologous SCT ≤ 3 months prior to study intervention initiation.
• In BMS-986458 + T-cell engager combination cohorts: Participants must not have prior alloSCT or solid organ transplantation, history of confirmed progressive multifocal leukoencephalopathy (PML); known or suspected history of hemophagocytic lymphohistiocytosis (HLH); known or suspected chronic active Epstein-Barr (EBV) infection.
• Participants must not have any condition, including significant acute or chronic medical illness, active or uncontrolled infection, or the presence of laboratory abnormalities, that places participants at unacceptable risk if participating in this study.
• Participants must not have known or suspected central nervous system involvement.
• Other protocol-defined Inclusion/Exclusion criteria apply.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 11 центров

• Mayo Clinic in Arizona - Phoenix — Phoenix
• City of Hope Comprehensive Cancer Center — Duarte
• Local Institution - 0068 — Jacksonville
• Moffitt Cancer Center — Tampa
• Dana-Farber Cancer Institute — Boston
• Mayo Clinic in Rochester, Minnesota — Rochester
• Local Institution - 0124 — Omaha
• Local Institution - 0047 — Lake Success
• … и ещё 3 центра

Италия · 9 центров

• Local Institution - 0094 — Bologna
• Local Institution - 0116 — Brescia
• Local Institution - 0098 — Milan
• Local Institution - 0113 — Milan
• Local Institution - 0112 — Pisa
• Local Institution - 0111 — Ravenna
• Local Institution - 0115 — Roma
• Local Institution - 0110 — Roma
• … и ещё 1 центр

Франция · 8 центров

• Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest — Bordeaux
• Local Institution - 0125 — Lyon
• Hopital Claude Huriez - CHU de Lille — Lille
• Gustave Roussy — Villejuif
• Henri Mondor Hospital — Créteil
• CHU SAINT ELOI - Departement Hematologie Clinique — Montpellier
• Hôpital Saint-Louis — Paris
• Institut Claudius Regaud — Toulouse

Испания · 6 центров

• Hospital Universitario Virgen de la Victoria — Málaga
• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital General Universitario Gregorio Marañon — Madrid
• Clinica Universidad de Navarra — Pamplona
• Hospital Universitario Fundación Jiménez Díaz — Madrid
• Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca — Salamanca

Германия · 5 центров

• Universitätsklinikum Münster - Albert Schweitzer Campus — Münster
• Universitaetsklinikum des Saarlandes — Homburg
• Universitätsklinikum Leipzig — Leipzig
• Helios Klinikum Berlin-Buch — Berlin
• Local Institution - 0070 — Essen

Китай · 4 центра

• Beijing Cancer hospital — Пекин
• Local Institution - 0084 — Гуанчжоу
• Local Institution - 0087 — Чжэнчжоу
• Local Institution - 0089 — Nanchang

Греция · 4 центра

• Local Institution - 0103 — Pátrai
• Local Institution - 0106 — Alexandroupoli
• Local Institution - 0107 — Athens
• Local Institution - 0102 — Athens

Япония · 4 центра

• Local Institution - 0090 — Nagoya
• Local Institution - 0091 — Chuo-ku
• Local Institution - 0086 — Chūō
• Local Institution - 0092 — Fukuoka

Чили · 3 центра

• Local Institution - 0118 — Antofagasta
• Local Institution - 0105 — Santiago
• Local Institution - 0109 — Santiago

Нидерланды · 3 центра

• Maastricht UMC+ — Maastricht
• Local Institution - 0121 — Amsterdam
• University Medical Center Groningen — Groningen

South Korea · 3 центра

• Local Institution - 0123 — Seoul
• Local Institution - 0077 — Seoul
• Local Institution - 0078 — Seoul

Швейцария · 3 центра

• Ospedale Regionale Bellinzona e Valli — Bellinzona
• University Hospital Basel — Basel
• Hopitaux Universitaires de Geneve (HUG) — Geneva

Великобритания · 3 центра

• Local Institution - 0071 — Southampton
• Local Institution - 0081 — Manchester
• Local Institution - 0072 — Edinburgh

Гонконг · 1 центр

• Local Institution - 0119 — Гонконг

Публикации

• Mortensen DS, Shunatona HP, Holmberg-Douglas N, Rhodes J, Da Silva D, Gamez J, Groza M, Zhu J, Christoforou A, Johnson SA, Khambatta G, Narla RK, Nimje RY, Huang D, Dodd DS, Griffin J, Miseo G, Whitefield B, Weiss DR, Rader J, Kuzu E, Leisten J, Lai C, Shi L, Del Rosario J, Dalvie D, Rolfe M, Zapf CW, Belmont P, Alexander M, Bence N, Groocock L. Discovery of BMS-986458, a Potent and Selective B-Ce PMID 41670385

Идентификаторы

NCT: NCT06090539 · CA123-1000 · 2023-506654-20 · U1111-1291-2654

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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