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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, drug levels, and preliminary biological and clinical activity of BMS-986458 as a single agent and in combination with anti-lymphoma agents in participants with relapsed/refractory non-Hodgkin Lymphoma.

Official Title
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A Phase 1, 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)

Conditions
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Relapsed/Refractory Non-Hodgkin Lymphoma

Intervention / Treatment
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* Drug: BMS-986458
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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)22 performance status ≥ 3. Participants with an inability to comply with listed restrictions, precautions and prohibited treatments. Participants must not have prior CAR-T, Cereblon-modulating drug or radiotherapy ≤ 4 weeks, systemic anticancer treatment ≤ 5 half-lives or 4 weeks, allogeneic SCT ≤ 6 months or autologous SCT ≤ 3 months prior to study intervention initiation. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A1<br>Single Agent | Drug: BMS-986458<br>* Specified dose on specified days.<br>|
| Experimental: Part A2<br>Combination Treatment | Drug: BMS-986458<br>* Specified dose on specified days.<br>Drug: Rituximab<br>* Specified dose on specified days.<br>|
| Experimental: Part B1<br>Single Agent | Drug: BMS-986458<br>* Specified dose on specified days.<br>|
| Experimental: Part B2<br>Combination Treatment | Drug: BMS-986458<br>* Specified dose on specified days.<br>Drug: Rituximab<br>* Specified dose on specified days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 2 years and 1 month | 
| Number of participants with AEs leading to discontiunation |  | Up to 2 years and 1 month | 
| Number of participants with AEs leading to death |  | Up to 2 years and 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 (AUC(0-T)) |  | Up to 4 months | 
| Number of participants with an overall response rate (ORR) according to the Lugano response criteria for Non-Hodgkin Lymphoma |  | Up to 2 years | 
| Duration of response (DOR) |  | Up to 2 years | 
| Time to response (TTR) |  | Up to 2 years | 
| Progression-free survival (PFS) |  | Up to 2 years | 
| Overall survival (OS) |  | Up to 2 years |