A Study of LY4152199 in Participants With Previously Treated B-cell Cancers and Leukemia

Launched by ELI LILLY AND COMPANY · Jul 28, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new drug called LY4152199 to see if it is safe and helpful for people who have certain types of B-cell cancers, such as different kinds of lymphoma and leukemia, who have already received treatment before. The study has two parts: first, it will find the best dose of the drug to give, and then it will test how well that dose works in treating these cancers.

People who might be eligible for this trial are adults aged 18 to 74 who have a good general health status and certain types of B-cell cancers that have come back or did not respond to previous treatments. Participants need to have measurable disease, which means the cancer can be tracked by tests or scans, and their organs must be working well enough to handle the treatment. During the trial, participants will receive the study drug and have regular check-ups, including lab tests and clinic visits, to monitor how they are doing and to watch for any side effects. It’s important to know that this trial is not currently recruiting, and there are some health conditions and prior treatments that might make someone ineligible, such as active infections, certain brain-related diseases, or recent stem cell transplants. Overall, this study aims to find new options for people with hard-to-treat B-cell cancers.

Gender

ALL

Eligibility criteria

• 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:
• • Participants with lymphoma and Richter transformation (RT) must have at least 1 bi-dimensionally measurable lesion or in the absence of measurable lymphadenopathy, documentation of bone marrow involvement, elevated immunoglobulin M (IgM) levels and/or lymphocytosis.
• • 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.
• • Phase 1b Dose Expansion (Cohort C) Participants
• • - Must have histologically confirmed diagnosis of relapsed/refractory B-cell malignancies as defined below per specific cohort. Transplant eligibility or ineligibility may be determined by the Investigator, who may consider factors such as age, overall fitness, comorbidities, and prior treatment history of the participant.
• • Cohort C1a: Transplant ineligible DLBCL (not otherwise specified (NOS), high-grade B-cell lymphoma, transformed from follicular lymphoma \[FL\]) that has failed or was intolerant to prior therapy. Burkitt lymphoma is excluded.
• • Cohort C1b: Transplant eligible DLBCL (NOS, high-grade B-cell lymphoma, transformed from FL) that has failed or was intolerant to prior therapy or no other treatment option after prior treatment in the opinion of the investigator. Burkitt lymphoma is excluded.
• • Cohort C1c: RT that has failed or was intolerant to prior therapy or no other treatment option in the opinion of the investigator.
• • Cohort C2: FL (Grades 1 to 3a) that has relapsed after or failed to respond to prior systemic treatment regimen.
• • Cohort C3: Mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), WM that has relapsed after or failed to respond to prior systemic treatment regimen.
• • Cohort C4: Chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) that has relapsed after or failed to respond to prior systemic treatment regimen.
• • Cohort C5: B-cell acute lymphoblastic leukemia (B-ALL) that has relapsed after or failed to respond to prior systemic treatment regimen.
• Exclusion Criteria:
• • All Participants
• • Known or suspected central nervous system (CNS) involvement by systemic lymphoma or leukemia.
• • 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.