A Phase I/II, 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 Identifier:
CA123-1000
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
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Study 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.
The efficacy-evaluable (EE) population included pts with ≥1 dose of BMS-986458, a baseline and post-baseline tumor assessment, clinical progression, or death. To present updated clinical findings from the dose-escalation part of CA123- 1000, a first-in-human, multicenter, open-label study of BMS-986458 in pts with R/R NHL.
Primary: To evaluate the safety and tolerability of BMS-986458 monotherapy and in combination with anti-lymphoma drugs in R/R NHL participants, and to determine RP2D. Secondary: To describe the effects of oral BMS-986458 monotherapy and combination with anti-lymphoma drugs in R/R NHL participants; to evaluate the preliminary efficacy of BMS-986458 monotherapy and combination with anti-lymphoma drugs in R/R NHL participants; and to characterize the plasma pharmacokinetic profiles of the combined administration.
To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of BMS-986458 administered either as a monotherapy or in combination with lymphoma treatment drugs in patients with relapsed or refractory non-Hodgkin lymphoma.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Lymphoma
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Drug: BMS-986458 Specified dose on specified days. Experimental: Part A2 Combination Treatment Drug: BMS-986458 Specified dose on specified days. Drug: Glofitamab/Obinutuzumab Specified dose on specified days Drug: Mosunetuzumab Specified dose on specified days Drug: Rituximab Specified dose on specified days. Experimental: Part B1 Single Agent Drug: BMS-986458 Specified dose on specified days. Experimental: Part B2 Combination Treatment Drug: BMS-986458 Specified dose on specified days. Drug: Rituximab Specified dose on specified days. Drug: Glofitamab/Obinutuzumab Specified dose on specified days Drug: Epcoritamab Specified dose on specified days Pts received 40, 80, or 160 mg BMS-986458 twice daily (BID) or 80, 160, or 260 mg once daily.
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Participants ≥ 18 years of age with frontline or R/R NHL.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.Pts with R/R DLBCL (de novo or transformed) or R/R FL (including FL 3b) with ≥2 prior regimens and met investigator-assessed treatment (tx) criteria were eligible.
- Participants must be 18 years of age or older, or of legal Age as defined by local regulations, and have R/R NHL (including DLBCL [i.e., nonspecific (NOS) DLBCL and diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 gene rearrangements] and FL).
- R/R DLBCL (primary) and FL 3b patients: have received at least 2 lines of prior therapy (e.g., first-line combination chemotherapy regimens containing rituximab, anthracyclines, alkylating agents and steroids, and at least one other treatment).
- R/R DLBCL (transformed lymphoma) patients: have received at least 2 lines of prior therapy after transformation; therefore, these patients must receive at least 2 standard DLBCL treatment regimens.
- R/R FL (excluding FL 3b) patients: have received at least 2 lines of prior therapy and meet the treatment criteria at enrollment according to investigator assessment.
- Participants must have measurable lesions, defined as: at least one FDG-avid lesion, and at least one two-dimensional measurable lesion with a transverse diameter >1.5 cm on computed tomography or magnetic resonance imaging cross-sectional images.
- Participants must accept and follow a pregnancy prevention plan.
- 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.Other protocol-defined Inclusion/Exclusion criteria apply. Performance status score ≥2 of the Eastern Cooperative Oncology Group (ECOG).
- Unable to comply with the restrictions, precautions and contraindicated treatments listed in Section 7.7, Concomitant Treatments.
- Prior to the start of the study intervention, the following criteria were met: previous CAR-T or radiotherapy ≤4 weeks, systemic anti-tumor therapy ≤5 half-lives or 4 weeks, alloSCT ≤6 months (only applicable to the BMS-986458 monotherapy or rituximab combination therapy cohort), or autoSCT ≤3 months.
- BMS-986458+T-cell connector combination therapy cohort: history of alloSCT or solid organ transplantation, history of confirmed progressive multifocal leukoencephalopathy (PML); history of known or suspected hemophagocytic lymphohistiocytosis (HLH); history of known or suspected chronic active Epstein-Barr virus (EBV) infection.
- Any condition that exposes participants to unacceptable risks when they participate in the study, including serious acute or chronic illness, active or uncontrolled infection, or abnormal laboratory test results.
- Participants had known or suspected central nervous system involvement.
- - 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.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Daniel Morillo Giles
Status
Recruiting
Condition(s) Treated at Site
Lymphoma