Clinical trial · Interventional
A Study to Assess BMS-986458 Alone and in Combination With Anti-lymphoma Agents in Relapsed/Refractory Non-Hodgkin Lymphomas
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)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 15, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260915-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Relapsed/Refractory Non-Hodgkin Lymphoma | Non-Hodgkin Lymphoma | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (6)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| BMS-986458 | Drug | — | UNRESOLVED |
| Epcoritamab | Drug | Epcoritamab | ALIAS |
| Glofitamab/Obinutuzumab | Drug | — | UNRESOLVED |
| Golcadomide | Drug | — | UNRESOLVED |
| Mosunetuzumab | Drug | Mosunetuzumab | ALIAS |
| Rituximab | Drug | Rituximab | ALIAS |
Design
Arms and outcomes
Arms (5)
- type
- EXPERIMENTAL
- label
- Part A1
- description
- Single Agent
- interventionNames
- Drug: BMS-986458
- type
- EXPERIMENTAL
- label
- Part A2
- description
- Combination Treatment
- interventionNames
- Drug: BMS-986458
- Drug: Rituximab
- Drug: Glofitamab/Obinutuzumab
- Drug: Mosunetuzumab
- type
- EXPERIMENTAL
- label
- Part B1
- description
- Single Agent
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (1)
- DERIVEDMortensen 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-Cell Lymphoma 6 Protein Ligand-Directed Degrader, for the Treatment of B-Cell Non-Hodgkin Lymphoma. J Med Chem. 2026 Feb 26;69(4):4424-4438. doi: 10.1021/acs.jmedchem.5c03123. Epub 2026 Feb 11. PMID 41670385