A Study of LY4152199 in Participants With Previously Treated B-cell Cancers and Leukemia (BAFFRontier-1)

Lilly

Status and phase: Not yet enrolling; Phase 1

Conditions: Waldenstrom Macroglobulinemia; Lymphoma, B-cell Marginal Zone; Lymphoma, Mantle-Cell; Lymphoma, Follicular; B-cell Lymphoma; Lymphoma, Large B-Cell, Diffuse; Leukemia, B-Cell; Burkitt Lymphoma; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell

Treatments: Drug: LY4152199 - IV; Drug: LY4152199 - SC

Study type: Interventional

Funder types: Industry

Identifiers

NCT07101328

27701

J6N-MC-JUCA (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to measure the safety and efficacy of LY4152199 in participants with previously treated B-cell lymphoma and leukemia. This study has two parts. In the first part, the study will find the best dose of the drug. In the second part, the study will see how well the best dose works in participants with certain types of B-cell cancer and leukemia.

Enrollment: 215 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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:
• 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.
• Participants with chronic lymphocytic leukemia (CLL) must have assessable disease in blood or bone marrow by flow cytometry or immunohistochemistry.
• 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 1a Dose Escalation (Cohort A) Participants

- Must have histologically confirmed relapsed/refractory B-cell malignancy.

Phase 1a Dose Optimization (Cohort B) Participants

- Must have histologically confirmed relapsed/refractory diffuse large B-cell lymphoma (DLBCL) de novo or transformed.

Exclusion criteria

All Participants

• 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). This exclusion criterion does not apply to participants seeking retreatment.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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215 participants in 2 patient groups

Phase 1A: Dose Escalation (Cohort A)

Experimental group

Description:

Escalating doses of LY4152199 administered intravenously (IV)

Treatment:

Drug: LY4152199 - IV

Phase 1A: Dose Optimization (Cohort B)

Experimental group

Description:

Two or more doses of LY4152199 (evaluated during dose escalation) administered SC

Treatment:

Drug: LY4152199 - SC