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.

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.

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

See Plan Description

See Plan Description