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

NCT07101328 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: 277012025-524180-20-00J6N-MC-JUCA
• Study Type: interventional
• Target: 215
• Locations: 12 countries
• Sites: 50

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.

Conditions

Lymphoma, Non-Hodgkin; B-cell Lymphoma; Lymphoma, Follicular; Lymphoma, B-cell Marginal Zone; Lymphoma, Mantle Cell; Waldenstrom Macroglobulinemia; Lymphoma, Large B-Cell, Diffuse

Keywords

B- cell activating factor receptor (BAFFR); Bispecific antibody

Outcome Measures

Primary Outcomes (1)

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

  Cycle 1 Day 1 through Cycle 2 Day 8 (35 days)

Secondary Outcomes (6)

• 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

• Phase 1 - Duration of Response (DOR)

  Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy

• Phase 1- Time to Response (TTR)

  Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy

Study Arms (3)

Phase 1: Dose Escalation (Cohort A) - DLBCL and FL

EXPERIMENTAL

Escalating doses of LY4152199 administered intravenously (IV)

Drug: LY4152199 - IV

Phase 1: Dose Optimization (Cohort B1) - DLBCL

EXPERIMENTAL

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

Drug: LY4152199 - IV

Phase 1: Dose Optimization (Cohort B2) - FL

EXPERIMENTAL

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

Drug: LY4152199 - IV

Interventions

LY4152199 - IV DRUG

Administered by IV infusion

Phase 1: Dose Escalation (Cohort A) - DLBCL and FL; Phase 1: Dose Optimization (Cohort B1) - DLBCL; Phase 1: Dose Optimization (Cohort B2) - FL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (50)

City of Hope

Duarte, California, 91010, United States

RECRUITING

University of Colorado Denver - School of Medicine - Anschutz Medical Campus

Aurora, Colorado, 80045-2559, United States

RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

Yale University School of Medicine - Yale Cancer Center

New Haven, Connecticut, 06520-8028, United States

RECRUITING

The University of Chicago Medical Center (UCMC)

Chicago, Illinois, 60637, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

NOT YET RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

NOT YET RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

NOT YET RECRUITING

New York University (NYU) Clinical Cancer Center

New York, New York, 10016, United States

RECRUITING

Weill Cornell Medicine

New York, New York, 10021, United States

RECRUITING

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 75244, United States

NOT YET RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Intermountain Healthcare

Salt Lake City, Utah, 84111, United States

NOT YET RECRUITING

Swedish Cancer Institute (SCI)

Seattle, Washington, 98104, United States

NOT YET RECRUITING

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

NOT YET RECRUITING

The Alfred Hospital

Melbourne, VIC, 3004, Australia

NOT YET RECRUITING

Linear Clinical Research

Nedlands, 6009, Australia

NOT YET RECRUITING

Lady Davis Institute for Medical Research Jewish General Hospital

Montreal, H3T 1E2, Canada

NOT YET RECRUITING

University Health Network (UHN) - Princess Margaret Cancer Centre

Toronto, M5G 1Z5, Canada

NOT YET RECRUITING

BC Cancer - Vancouver

Vancouver, V5Z 1L3, Canada

NOT YET RECRUITING

Aarhus University Hospital

Aarhus, N 8200, Denmark

NOT YET RECRUITING

Center for Cancer and Organ Diseases - Rigshospitalet

Copenhagen, 2100, Denmark

NOT YET RECRUITING

CHU de Lille - Hopital Claude Huriez

Lille, 59037, France

NOT YET RECRUITING

AP-HP Hopital Saint-Louis

Paris, 75010, France

NOT YET RECRUITING

Charite Universitaetsmedizin Berlin

Berlin, 10117, Germany

NOT YET RECRUITING

LMU Klinikum Muenchen-Campus Grosshadern

München, 80336, Germany

NOT YET RECRUITING

Universitaetsklinikum Muenster

Münster, 48149, Germany

NOT YET RECRUITING

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola

Bologna, 40138, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, 80131, Italy

NOT YET RECRUITING

Istituto Clinico Humanitas

Rozzano, 20089, Italy

NOT YET RECRUITING

National Cancer Center Hospital East

Chiba, 277-8577, Japan

NOT YET RECRUITING

Okayama University Hospital

Okayama, 700-8558,, Japan

NOT YET RECRUITING

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

NOT YET RECRUITING

Pratia MCM Krakow

Krakow, 30-727, Poland

NOT YET RECRUITING

AIDPORT Sp. z o.o.

Skorzewo, 60-185, Poland

NOT YET RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

NOT YET RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

NOT YET RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

NOT YET RECRUITING

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, 08908, Spain

NOT YET RECRUITING

South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

NOT YET RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

NOT YET RECRUITING

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 9DU, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Study Officials

• Call 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

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: August 3, 2025
• Study Start: May 28, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): September 1, 2029
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); JP (3); KR (2); DE (3); IT (3); DK (2); PL (2); GB (2); AU (2); CA (3); ES (3); US (23)