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)
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
Study locations (14)
Mayo Clinic in Arizona - Phoenix
Phoenix, Arizona, 85054
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Local Institution - 0068
Jacksonville, Florida, 32224
Moffitt Cancer Center
Tampa, Florida, 33612
Local Institution - 0014
Fairway, Kansas, 66205
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Mayo Clinic in Rochester, Minnesota
Rochester, Minnesota, 55905
Local Institution - 0124
Omaha, Nebraska, 68105
Local Institution - 0047
Lake Success, New York, 11042
Local Institution - 0037
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Local Institution - 0040
Pittsburgh, Pennsylvania, 15232
Local Institution - 0045
Providence, Rhode Island, 02903
Local Institution - 0024
Milwaukee, Wisconsin, 53226
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)