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

NCT06090539 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CA123-1000
• Study Type: interventional
• Target: 308
• Locations: 13 countries
• Sites: 65

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.

Conditions

Relapsed/Refractory Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (5)

• 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 Day 28

• 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 Outcomes (9)

• Maximum concentration (Cmax)

  Up to 4 months

• Time of maximum concentration (Tmax)

  Up to 4 months

• Area under the plasma concentration-time curve within a dosing interval [AUC(TAU)]

  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

Study Arms (4)

Part A1

EXPERIMENTAL

Single Agent

Drug: BMS-986458

Part A2

EXPERIMENTAL

Combination Treatment

Drug: BMS-986458; Drug: Rituximab; Drug: Glofitamab/Obinutuzumab; Drug: Mosunetuzumab

Part B1

EXPERIMENTAL

Single Agent

Drug: BMS-986458

Part B2

EXPERIMENTAL

Combination Treatment

Drug: BMS-986458; Drug: Rituximab; Drug: Glofitamab/Obinutuzumab; Drug: Mosunetuzumab

Interventions

Rituximab DRUG

Specified dose on specified days.

Part A2; Part B2

BMS-986458 DRUG

Specified dose on specified days.

Part A1; Part A2; Part B1; Part B2

Glofitamab/Obinutuzumab DRUG

Specified dose on specified days

Part A2; Part B2

Mosunetuzumab DRUG

Specified dose on specified days

Part A2; Part B2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (65)

Mayo Clinic in Arizona - Phoenix

Phoenix, Arizona, 85054, United States

RECRUITING

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

Local Institution - 0068

Jacksonville, Florida, 32224, United States

NOT YET RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Local Institution - 0014

Fairway, Kansas, 66205, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Mayo Clinic in Rochester, Minnesota

Rochester, Minnesota, 55905, United States

RECRUITING

Local Institution - 0124

Omaha, Nebraska, 68105, United States

NOT YET RECRUITING

Local Institution - 0047

Lake Success, New York, 11042, United States

COMPLETED

Local Institution - 0037

New York, New York, 10016, United States

NOT YET RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Local Institution - 0040

Pittsburgh, Pennsylvania, 15232, United States

NOT YET RECRUITING

Local Institution - 0045

Providence, Rhode Island, 02903, United States

NOT YET RECRUITING

Local Institution - 0024

Milwaukee, Wisconsin, 53226, United States

NOT YET RECRUITING

Local Institution - 0118

Antofagasta, AN, 1240000, Chile

NOT YET RECRUITING

Local Institution - 0105

Santiago, Metropolitana de Santiago, 7580206, Chile

NOT YET RECRUITING

Local Institution - 0109

Santiago, Santiago Metropolitan, 8420383, Chile

NOT YET RECRUITING

Local Institution - 0088

Beijing, Beijing Municipality, 100142, China

NOT YET RECRUITING

Local Institution - 0089

Nanchang, Jiangxi, 330006, China

NOT YET RECRUITING

Local Institution - 0084

Guangzhou, 510060, China

NOT YET RECRUITING

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, Aquitaine, 33076, France

RECRUITING

Hopital Claude Huriez - CHU de Lille

Lille, Nord, 59000, France

RECRUITING

Gustave Roussy

Villejuif, Paris, 94800, France

RECRUITING

Henri Mondor Hospital

Créteil, Val-de-Marne, 94010, France

RECRUITING

CHU SAINT ELOI - Departement Hematologie Clinique

Montpellier, 34295, France

RECRUITING

Hôpital Saint-Louis

Paris, 75010, France

RECRUITING

Institut Claudius Regaud

Toulouse, 31059, France

RECRUITING

Universitätsklinikum Münster - Albert Schweitzer Campus

Münster, North Rhine-Westphalia, 48149, Germany

RECRUITING

Universitaetsklinikum des Saarlandes

Homburg, Saarland, 66424, Germany

RECRUITING

Universitätsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

RECRUITING

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

RECRUITING

Local Institution - 0070

Essen, 45147, Germany

NOT YET RECRUITING

Local Institution - 0103

Pátrai, Achaḯa, 26504, Greece

NOT YET RECRUITING

Local Institution - 0106

Alexandroupoli, Evros, 68100, Greece

NOT YET RECRUITING

Local Institution - 0107

Athens, 10676, Greece

NOT YET RECRUITING

Local Institution - 0102

Athens, 11 527, Greece

NOT YET RECRUITING

Local Institution - 0094

Bologna, 40138, Italy

NOT YET RECRUITING

Local Institution - 0116

Brescia, 25123, Italy

NOT YET RECRUITING

Local Institution - 0098

Milan, 20132, Italy

NOT YET RECRUITING

Local Institution - 0113

Milan, 20133, Italy

NOT YET RECRUITING

Local Institution - 0112

Pisa, 56126, Italy

NOT YET RECRUITING

Local Institution - 0111

Ravenna, 48121, Italy

NOT YET RECRUITING

Local Institution - 0115

Roma, 00144, Italy

NOT YET RECRUITING

Local Institution - 0110

Roma, 00168, Italy

NOT YET RECRUITING

Local Institution - 0097

Verona, 37134, Italy

NOT YET RECRUITING

Local Institution - 0090

Nagoya, Aichi-ken, 4668560, Japan

NOT YET RECRUITING

Local Institution - 0091

Chuo-ku, Tokyo, 104-0045, Japan

NOT YET RECRUITING

Local Institution - 0086

Chūō, Yamanashi, 4093898, Japan

NOT YET RECRUITING

Local Institution - 0092

Fukuoka, 812-8582, Japan

NOT YET RECRUITING

Maastricht UMC+

Maastricht, Limburg, 6229 HX, Netherlands

RECRUITING

Local Institution - 0121

Amsterdam, North Holland, 1981 HV, Netherlands

NOT YET RECRUITING

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

Local Institution - 0077

Seoul, Seoul Teugbyeolsi, 06351, South Korea

NOT YET RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, Andalusia, 29010, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [Barcelona], 08035, Spain

RECRUITING

Local Institution - 0069

Madrid, Madrid, Comunidad de, 28009, Spain

NOT YET RECRUITING

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca

Salamanca, 37007, Spain

RECRUITING

Ospedale Regionale Bellinzona e Valli

Bellinzona, Canton Ticino, 6500, Switzerland

RECRUITING

University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

Hopitaux Universitaires de Geneve (HUG)

Geneva, 1205, Switzerland

RECRUITING

Local Institution - 0071

Southampton, Hampshire, SO16 0YD, United Kingdom

NOT YET RECRUITING

Local Institution - 0081

Manchester, Lancashire, M20 4BX, United Kingdom

NOT YET RECRUITING

Local Institution - 0072

Edinburgh, Midlothian, EH4 2XU, United Kingdom

NOT YET RECRUITING

Related Publications (1)

• Mortensen 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 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Rituximab; glofitamab; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Central Study Contacts

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

CONTACT

855-907-3286; Clinical.Trials@bms.com

First line of the email MUST contain NCT # and Site #.

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2023
• First Posted: October 19, 2023
• Study Start: December 29, 2023
• Primary Completion (Estimated): October 28, 2027
• Study Completion (Estimated): October 28, 2028
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

FR (7); GB (3); JP (4); CN (3); GR (4); IT (9); KR (1); CL (3); US (14); DE (5); ES (6); CH (3); NL (3)