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)
Overview
- Phase
- Phase 1
- Intervention
- BMS-986458
- Conditions
- Relapsed/Refractory Non-Hodgkin Lymphoma
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 308
- Locations
- 99
- Primary Endpoint
- Number of participants with adverse events (AEs)
- Status
- Recruiting
- Last Updated
- 18 days ago
Overview
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.
Investigators
Eligibility Criteria
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 ≥
- •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.
Arms & Interventions
Part B2
Combination Treatment
Intervention: BMS-986458
Part B2
Combination Treatment
Intervention: Rituximab
Part A2
Combination Treatment
Intervention: Glofitamab/Obinutuzumab
Part B2
Combination Treatment
Intervention: Glofitamab/Obinutuzumab
Part A2
Combination Treatment
Intervention: BMS-986458
Part B2
Combination Treatment
Intervention: Mosunetuzumab
Part A2
Combination Treatment
Intervention: Rituximab
Part A1
Single Agent
Intervention: BMS-986458
Part A2
Combination Treatment
Intervention: Mosunetuzumab
Part B1
Single Agent
Intervention: BMS-986458
Outcomes
Primary Outcomes
Number of participants with adverse events (AEs)
Time Frame: Up to 2 years and 1 month
Number of participants with serious adverse events (SAEs)
Time Frame: Up to 2 years and 1 month
Number of participants with AEs leading to death
Time Frame: Up to 2 years and 1 month
Number of participants with AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria
Time Frame: Up to Day 28
Number of participants with AEs leading to discontiunation
Time Frame: Up to 2 years and 1 month
Secondary Outcomes
- 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)