Relapsed/Refractory Non-Hodgkin Lymphoma
Conditions
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 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
DRUGBMS-986458
Specified dose on specified days.
DRUGRituximab
Specified dose on specified days.
DRUGGlofitamab/Obinutuzumab
Specified dose on specified days
DRUGMosunetuzumab
Specified dose on specified days
DRUGEpcoritamab
Specified dose on specified days
DRUGGolcadomide
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) | 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 AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria | Up to Day 28 | — |
| Number of participants with AEs leading to death | Up to 2 years and 1 month | — |
| Number of participants with AEs leading to discontinuation | 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 | Up to 2 years and 11 month | Part B2 Cohort B only |
Secondary
| Measure | Time frame |
|---|---|
| Maximum concentration (Cmax) | Up to 4 months |
| Time of maximum concentration (Tmax) | Up to 4 months |
| Area under the plasma concentration-time curve within a dosing interval [AUC(TAU)] | 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 | 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 | Up to 2 years |
| Duration of response (DOR) | Up to 3 years |
| Time to response (TTR) | Up to 3 years |
| Progression-free survival (PFS) | Up to 3 years |
| Overall survival (OS) | Up to 3 years |
Countries
Chile, China, France, Germany, Greece, Hong Kong, Italy, Japan, Netherlands, South Korea, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed