A Study of LY4152199 in Participants With Previously Treated B-cell Malignancies (BAF_FRontier-1 )
Purpose
The purpose of this study is to find the best dose of the drug and measure the safety and efficacy of LY4152199 in participants with previously treated B-cell malignancies. Participants will have the option to continue taking LY4152199 until the study ends.
Conditions
- Lymphoma, Non-Hodgkin
- B-cell Lymphoma
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma, Follicular
- Lymphoma, B-cell Marginal Zone
- Waldenstrom Macroglobulinemia
- Lymphoma, Mantle Cell
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Must have a diagnosis of either follicular lymphoma or diffuse large B-cell lymphoma. - Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. - Estimated life expectancy of greater than or equal to (≥)12 weeks as judged by the Investigator. - Participants with select tumor types must have measurable or assessable disease as defined below: - Participants with lymphoma must have at least 1 bi-dimensionally measurable lesion or in the absence of measurable lymphadenopathy, documentation of bone marrow involvement. - Participants with Waldenstrom macroglobulinemia (WM) must have measurable disease, defined as the presence of serum IgM with a minimum IgM level of greater than (>)2 times (×) upper limit of normal (ULN) based on local laboratory testing. - Must be able to comply with inpatient/outpatient treatment, laboratory monitoring, and required clinic visits for the duration of trial participation. - Must have adequate organ function. Phase 1 Dose Escalation (Cohort A) Participants - Must have histologically confirmed relapsed/refractory B-cell malignancy. Phase 1 Dose Optimization (Cohort B) Participants - Must have histologically confirmed relapsed/refractory diffuse large B-cell lymphoma (DLBCL) de novo or transformed from follicular lymphoma (FL).
Exclusion Criteria
All Participants - Known or suspected peripheral blood involvement by malignant cells with an absolute lymphocyte count of greater than or equal to (≥) 5000 cells per microliter (μL). - Known or suspected central nervous system (CNS) involvement by systemic lymphoma. - Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease - Any unresolved toxicities from prior therapy greater than National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 2 at the time of starting trial treatment except for alopecia. - Autologous stem cell transplantation within 100 days of this study for post autologous transplant individuals. - Residual symptoms of neurotoxicity or cytopenias from prior chimeric antigen receptor T-cell therapy (CAR-T) or bispecifics. Exception: Cytopenia related to prior CAR-T or bispecifics allowed if they meet the adequate organ function criteria. - Known or suspected history of macrophage activation syndrome or hemophagocytic lymphohistiocytosis (HLH). - Active second malignancies, unless in remission, with life expectancy greater than 2 years with Sponsor approval. - History of autoimmune disease - Significant cardiovascular disease - Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection (except for fungal nail infection), or other clinically significant active disease process - Vaccination with a live vaccine within 4 weeks prior to signing informed consent form (ICF). - Have current or had a history of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins). - Prior treatment with B-cell activating factor receptor (BAFF-R) directed therapies (e.g., monoclonal antibody, CAR-T or bispecific antibody). - Pregnant and/or planning to breastfeed during the trial or within 90 days of the last dose of study intervention. - Known hypersensitivity to any component or excipient of LY4152199.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase 1: Dose Escalation (Cohort A) - DLBCL and FL |
Escalating doses of LY4152199 administered intravenously (IV) |
|
|
Experimental Phase 1: Dose Optimization (Cohort B1) - DLBCL |
Two or more doses of LY4152199 (evaluated during dose escalation) administered IV |
|
|
Experimental Phase 1: Dose Optimization (Cohort B2) - FL |
Two or more doses of LY4152199 (evaluated during dose escalation) administered IV |
|
Recruiting Locations
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Eli Lilly and Company
Study Contact
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or1-317-615-4559
LillyTrials@Lilly.com