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

Phase 1

Recruiting

• Conditions: Relapsed/Refractory Non-Hodgkin Lymphoma
• Interventions: Drug: BMS-986458; Drug: Rituximab; Drug: Glofitamab/Obinutuzumab; Drug: Mosunetuzumab

• 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 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-13
• Study First Submitted QC: 2023-10-13
• Study First Posted: 2023-10-19
• Study Start: 2023-12-29
• Status Verified: 2025-06
• Last Update Submitted: 2025-07-02
• Last Update Posted: 2025-07-04
• Primary Completion: 2027-10-28
• Study Completion: 2028-10-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 308

Inclusion Criteria

• 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.

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part A1	BMS-986458	Single Agent
Part A2	BMS-986458	Combination Treatment
Part A2	Mosunetuzumab	Combination Treatment
Part B2	Rituximab	Combination Treatment
Part A2	Rituximab	Combination Treatment
Part A2	Glofitamab/Obinutuzumab	Combination Treatment
Part B1	BMS-986458	Single Agent
Part B2	BMS-986458	Combination Treatment
Part B2	Mosunetuzumab	Combination Treatment
Part B2	Glofitamab/Obinutuzumab	Combination Treatment

Primary Outcome Measures

Name	Time	Method
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 leading to death	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 discontiunation	Up to 2 years and 1 month

Secondary Outcome Measures

Name	Time	Method
Area under the plasma concentration-time curve within a dosing interval [AUC(TAU)]	Up to 4 months
Maximum concentration (Cmax)	Up to 4 months
Time of maximum concentration (Tmax)	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

Trial Locations

Locations (30)

Local Institution - 0067; 🇺🇸 Phoenix, Arizona, United States

Local Institution - 0027; 🇺🇸 Tampa, Florida, United States

Local Institution - 0014; 🇺🇸 Fairway, Kansas, United States

Local Institution - 0066; 🇺🇸 Rochester, Minnesota, United States

Local Institution - 0040; 🇺🇸 Pittsburgh, Pennsylvania, United States

Local Institution - 0057; 🇫🇷 Bordeaux, Aquitaine, France

CHU SAINT ELOI - Departement Hematologie Clinique; 🇫🇷 Montpellier, France

Local Institution - 0058; 🇫🇷 Paris, France

Local Institution - 0069; 🇪🇸 Madrid, Madrid, Comunidad De, Spain

Hopitaux Universitaires de Geneve (HUG); 🇨🇭 Geneve, Switzerland

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