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RecruitingInterventionalPhase 1/Phase 2

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)

NCT ID: NCT06090539Sponsor: Bristol-Myers SquibbLast updated: 2026-04-14

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.

Arms & interventions

  • DrugBMS-986458

    Specified dose on specified days.

  • DrugRituximab

    Specified dose on specified days.

  • DrugGlofitamab/Obinutuzumab

    Specified dose on specified days

  • DrugMosunetuzumab

    Specified dose on specified days

Outcome measures

Primary

  • 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 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

  • Number of participants with AEs leading to death

    Time frame: Up to 2 years and 1 month

Secondary

  • Maximum concentration (Cmax)

    Time frame: Up to 4 months

  • Time of maximum concentration (Tmax)

    Time frame: Up to 4 months

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

    Time frame: 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

    Time frame: 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

    Time frame: Up to 2 years

  • Duration of response (DOR)

    Time frame: Up to 3 years

  • Time to response (TTR)

    Time frame: Up to 3 years

  • Progression-free survival (PFS)

    Time frame: Up to 3 years

  • Overall survival (OS)

    Time frame: Up to 3 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (14)

Mayo Clinic in Arizona - Phoenix

Phoenix, Arizona, 85054

Recruiting
Javier Munoz, Site 0067 · Contact

City of Hope Comprehensive Cancer Center

Duarte, California, 91010

Recruiting
Avyakta Kallam, Site 0020 · Contact

Local Institution - 0068

Jacksonville, Florida, 32224

Not Yet Recruiting
Site 0068 · Contact

Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting
Bijal Shah, Site 0027 · Contact

Local Institution - 0014

Fairway, Kansas, 66205

Not Yet Recruiting
Site 0014 · Contact

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting
David Qualls, Site 0044 · Contact

Mayo Clinic in Rochester, Minnesota

Rochester, Minnesota, 55905

Recruiting
Yucai Wang, Site 0066 · Contact

Local Institution - 0124

Omaha, Nebraska, 68105

Not Yet Recruiting
Site 0124 · Contact

Local Institution - 0047

Lake Success, New York, 11042

Completed

Local Institution - 0037

New York, New York, 10016

Not Yet Recruiting
Site 0037 · Contact

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting
Jennifer Lue, Site 0046 · Contact

Local Institution - 0040

Pittsburgh, Pennsylvania, 15232

Not Yet Recruiting
Site 0040 · Contact

Local Institution - 0045

Providence, Rhode Island, 02903

Not Yet Recruiting
Site 0045 · Contact

Local Institution - 0024

Milwaukee, Wisconsin, 53226

Not Yet Recruiting
Site 0024 · Contact

References

  • 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.(PubMed)