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

Official title

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)

Overview

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.

Interventions

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

Primary outcome measures

• Number of participants with adverse events (AEs) [Time frame: Up to 2 years and 1 month]
• Number of participants with serious adverse events (SAEs) [Time frame: Up to 2 years and 1 month]
• Number of participants with AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria [Time frame: Up to Day 28]
• Number of participants with AEs leading to death [Time frame: Up to 2 years and 1 month]
• Number of participants with AEs leading to discontinuation [Time frame: 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 [Time frame: Up to 2 years and 11 month]

Secondary outcome measures (9)

• Maximum concentration (Cmax) [Time frame: Up to 4 months]
• Time of maximum concentration (Tmax) [Time frame: Up to 4 months]
• Area under the plasma concentration-time curve within a dosing interval [AUC(TAU)] [Time frame: 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 [Time frame: 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 [Time frame: Up to 2 years]
• Duration of response (DOR) [Time frame: Up to 3 years]
• Time to response (TTR) [Time frame: Up to 3 years]
• Progression-free survival (PFS) [Time frame: Up to 3 years]
• Overall survival (OS) [Time frame: Up to 3 years]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• 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
• … and 3 more centers

Italy · 9 centers

• 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
• … and 1 more center

France · 8 centers

• 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

Spain · 6 centers

• 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

Germany · 5 centers

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

China · 4 centers

• Beijing Cancer hospital — Beijing
• Local Institution - 0084 — Guangzhou
• Local Institution - 0087 — Zhengzhou
• Local Institution - 0089 — Nanchang

Greece · 4 centers

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

Japan · 4 centers

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

Chile · 3 centers

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

Netherlands · 3 centers

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

South Korea · 3 centers

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

Switzerland · 3 centers

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

United Kingdom · 3 centers

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

Hong Kong · 1 center

• Local Institution - 0119 — Hong Kong

Publications

• 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

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗