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NCT Number: NCT07101328

A Study of LY4152199 in Participants With Previously Treated B-cell Malignancies (BAF_FRontier-1 )

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.

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

LY4152199 - IV

Drug

Administered by IV infusion

Primary outcomes

  1. Phase 1 - Number of Participants with Dose Limiting Toxicities (DLT) of LY4152199

    Time frame: Cycle 1 Day 1 through Cycle 2 Day 8 (35 days)

Secondary outcomes

  1. Phase 1 - Pharmacokinetics (PK): Area under the Concentration versus Time Curve (AUC) of LY4152199

    Time frame: Baseline up to approximately 91 weeks

  2. Phase 1- PK: Maximum drug Concentration (Cmax) of LY4152199

    Time frame: Baseline up to approximately 91 weeks

  3. Phase 1 - Overall Response Rate (ORR): Percentage of Participants with Best Overall Response (BOR) of Partial Response (PR) or Better.

    Time frame: 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.

  4. Phase 1 - Duration of Response (DOR)

    Time frame: 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

  5. Phase 1- Time to Response (TTR)

    Time frame: 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)

  6. Phase 1 - Progression Free Survival (PFS)

    Time frame: 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

Study contacts

Contact information is provided by the study sponsor or research team.

Physicians interested in becoming principal investigators please contact

CONTACT

[email protected]

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

[email protected]

1-317-615-4559

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

BAF_FRontier-1, A First-in-Human, Phase 1 Trial to Assess Safety, Tolerability, and Preliminary Efficacy of LY4152199, a B-cell Activation Factor Receptor (BAFF-R) T-Cell Engager Bispecific Antibody in Adult Participants With Previously Treated B-cell Malignancies

Acronym: BAF_FRontier-1

Important dates

Study start
2026
Primary completion
2027
Study completion
2029
First posted
Aug 3, 2025
Registry last updated
Jul 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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