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

Bristol-Myers Squibb (BMS)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Relapsed/Refractory Non-Hodgkin Lymphoma

Treatments: Drug: Rituximab; Drug: BMS-986458

Study type: Interventional

Funder types: Industry

Identifiers

NCT06090539

CA123-1000

Details and patient eligibility

About

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 (LDD) of BCL6 (BCL6 LDD), as a single agent and in combination with anti-lymphoma agents in participants with relapsed/refractory non-Hodgkin Lymphoma.

Enrollment: 273 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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, 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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273 participants in 4 patient groups

Part A1

Experimental group

Description:

Single Agent

Treatment:

Drug: BMS-986458

Part A2

Experimental group

Description:

Combination Treatment

Treatment:

Drug: BMS-986458

Drug: Rituximab

Part B1

Experimental group

Description:

Single Agent

Treatment:

Drug: BMS-986458

Part B2

Experimental group

Description:

Combination Treatment

Treatment:

Drug: BMS-986458

Drug: Rituximab