A Study to Assess BMS-986458 Alone and in Combination With Anti-lymphoma Agents in Relapsed/Refractory Non-Hodgkin Lymphomas
- Conditions
- Relapsed/Refractory Non-Hodgkin Lymphoma
- Interventions
- Drug: BMS-986458Drug: Rituximab
- Registration Number
- NCT06090539
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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 (LDD) of BCL6 (BCL6 LDD), as a single agent and in combination with anti-lymphoma agents in participants with relapsed/refractory non-Hodgkin Lymphoma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 273
-
Participants ≥ 18 years of age with R/R NHL (including DLBCL [ie, DLBCL not otherwise specified (NOS) and diffuse large B-Cell lymphoma/high-grade B-Cell lymphoma with MYC and BCL2 rearrangements], and FL):
- For R/R DLBCL (de novo) and FL 3b: following at least 2 prior lines of therapy (eg, first-line combination chemotherapy regimen containing rituximab, anthracycline, an alkylating agent, and steroids and at least one additional treatment).
- For R/R DLBCL (transformed lymphoma): following at least 2 prior lines of therapy which must have been administered after transformation.
- For R/R FL (except for FL 3b): following at least 2 prior lines of therapy and meeting treatment criteria at the time of enrollment based on investigator´s assessment.
-
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.
- 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, Cereblon-modulating drug or radiotherapy ≤ 4 weeks, systemic anticancer treatment ≤ 5 half-lives or 4 weeks, allogeneic SCT ≤ 6 months or autologous SCT ≤ 3 months prior to study intervention initiation.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part B1 BMS-986458 Single Agent Part B2 Rituximab Combination Treatment Part A1 BMS-986458 Single Agent Part B2 BMS-986458 Combination Treatment Part A2 BMS-986458 Combination Treatment Part A2 Rituximab Combination Treatment
- Primary Outcome Measures
Name Time Method Number of participants with AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria Up to 2 years and 1 month Number of participants with AEs leading to discontiunation Up to 2 years and 1 month Number of participants with serious adverse events (SAEs) Up to 2 years and 1 month Number of participants with adverse events (AEs) Up to 2 years and 1 month Number of participants with AEs leading to death Up to 2 years and 1 month
- Secondary Outcome Measures
Name Time Method Time of maximum concentration (Tmax) Up to 4 months Number of participants with an overall response rate (ORR) according to the Lugano response criteria for Non-Hodgkin Lymphoma Up to 2 years Progression-free survival (PFS) Up to 2 years Overall survival (OS) Up to 2 years Area under the plasma concentration-time curve (AUC(0-T)) Up to 4 months Duration of response (DOR) Up to 2 years Maximum concentration (Cmax) Up to 4 months Time to response (TTR) Up to 2 years
Trial Locations
- Locations (22)
Universitätsklinikum Leipzig
🇩🇪Leipzig, Sachsen, Germany
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Northwell Health/ RJ Zuckerberg Cancer Center
🇺🇸Lake Success, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Hopital Claude Huriez - CHU de Lille
🇫🇷Lille, Nord, France
Gustave Roussy
🇫🇷Villejuif, Paris, France
CHU SAINT ELOI-Département d'Hématologie Clinique
🇫🇷Montpellier, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Universitätsklinikum Münster - Albert Schweitzer Campus
🇩🇪Münster, Nordrhein-Westfalen, Germany
Universitaetsklinikum des Saarlandes
🇩🇪Homburg, Saarland, Germany
Helios Klinikum Berlin-Buch
🇩🇪Berlin, Germany
Maastricht UMC+
🇳🇱Maastricht, Limburg, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Andalucía, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca
🇪🇸Salamanca, Spain
Ospedale Regionale Bellinzona e Valli
🇨🇭Bellinzona, Ticino, Switzerland
University Hospital Basel
🇨🇭Basel, Switzerland
Hôpitaux Universitaire de Genève
🇨🇭Genève, Switzerland