B-cell Lymphoma, Lymphoma, B-cell Marginal Zone, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle Cell, Lymphoma, Non-Hodgkin, Waldenstrom Macroglobulinemia
Conditions
Keywords
B- cell activating factor receptor (BAFFR), Bispecific antibody
Brief summary
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.
Interventions
DRUGLY4152199 - IV
Administered by IV infusion
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1 - Number of Participants with Dose Limiting Toxicities (DLT) of LY4152199 | Cycle 1 Day 1 through Cycle 2 Day 8 (35 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 - Pharmacokinetics (PK): Area under the Concentration versus Time Curve (AUC) of LY4152199 | Baseline up to approximately 91 weeks | — |
| Phase 1- PK: Maximum drug Concentration (Cmax) of LY4152199 | Baseline up to approximately 91 weeks | — |
| Phase 1 - Overall Response Rate (ORR): Percentage of Participants with Best Overall Response (BOR) of Partial Response (PR) or Better. | Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy | Assessed by the Investigator per disease-specific response criteria as appropriate to disease indication. |
| Phase 1 - Duration of Response (DOR) | Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy | Time between the date of first documented response (PR or better) to the date of first disease progression or death due to any cause, whichever occurs first |
| Phase 1- Time to Response (TTR) | Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy | Time from first dose date (or randomization date for the dose optimization cohort) to the date of first documented response (PR or better) |
| Phase 1 - Progression Free Survival (PFS) | Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy | Time from first dose date (or randomization date for the dose optimization cohort) to the date of first documented disease progression or death due to any cause, whichever occurs first |
Countries
Australia, Canada, Denmark, France, Germany, Italy, Japan, Poland, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACTPhysicians interested in becoming principal investigators please contact
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed