Clinical trial NCT06090539: A Study to Assess BMS-986458 Alone and in Combination With Anti-lymphoma Agents in Relapsed/Refractory Non-Hodgkin Lymphomas
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Non-Hodgkin Lymphoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2023-10-19
Enrollment: 273
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Up to 2 years and 1 month
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Up to 2 years and 1 month
measure: Number of participants with AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria
timeFrame: Up to 2 years and 1 month
measure: Number of participants with AEs leading to discontiunation
timeFrame: Up to 2 years and 1 month
measure: Number of participants with AEs leading to death
timeFrame: Up to 2 years and 1 month
Secondary outcomes:
measure: Maximum concentration (Cmax)
timeFrame: Up to 4 months
measure: Time of maximum concentration (Tmax)
timeFrame: Up to 4 months
measure: Area under the plasma concentration-time curve (AUC(0-T))
timeFrame: Up to 4 months
measure: Number of participants with an overall response rate (ORR) according to the Lugano response criteria for Non-Hodgkin Lymphoma
timeFrame: Up to 2 years
measure: Duration of response (DOR)
timeFrame: Up to 2 years
measure: Time to response (TTR)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Lake Success
country: United States
facility: Northwell Health/ RJ Zuckerberg Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Lille
country: France
facility: Hopital Claude Huriez - CHU de Lille
state: Nord
city: Villejuif
country: France
facility: Gustave Roussy
state: Paris
city: Montpellier
country: France
facility: CHU SAINT ELOI-Département d'Hématologie Clinique
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Münster
country: Germany
facility: Universitätsklinikum Münster - Albert Schweitzer Campus
state: Nordrhein-Westfalen
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
state: Saarland
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
state: Sachsen
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
state: Limburg
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
state: Andalucía
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale Bellinzona e Valli
state: Ticino
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Genève
country: Switzerland
facility: Hôpitaux Universitaire de Genève
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: