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

Official 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

Overview

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

• Drug LY4152199 - IV
  Administered by IV infusion

Primary outcome measures

• 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 outcome measures (6)

• Phase 1 - Pharmacokinetics (PK): Area under the Concentration versus Time Curve (AUC) of LY4152199 [Time frame: Baseline up to approximately 91 weeks]
• Phase 1- PK: Maximum drug Concentration (Cmax) of LY4152199 [Time frame: 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. [Time frame: Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy]
• Phase 1 - Duration of Response (DOR) [Time frame: Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy]
• Phase 1- Time to Response (TTR) [Time frame: Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy]
• Phase 1 - Progression Free Survival (PFS) [Time frame: Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 23 centers

• City of Hope — Duarte
• University of Colorado Denver - School of Medicine - Anschutz Medical Campus — Aurora
• Colorado Blood Cancer Institute — Denver
• Yale University School of Medicine - Yale Cancer Center — New Haven
• The University of Chicago Medical Center (UCMC) — Chicago
• University of Iowa — Iowa City
• University of Kansas Cancer Center — Kansas City
• Massachusetts General Hospital — Boston
• … and 15 more centers

Canada · 3 centers

• Lady Davis Institute for Medical Research Jewish General Hospital — Montreal
• University Health Network (UHN) - Princess Margaret Cancer Centre — Toronto
• BC Cancer - Vancouver — Vancouver

Germany · 3 centers

• Charite Universitaetsmedizin Berlin — Berlin
• LMU Klinikum Muenchen-Campus Grosshadern — München
• Universitaetsklinikum Muenster — Münster

Italy · 3 centers

• IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola — Bologna
• Istituto Nazionale Tumori IRCCS Fondazione G. Pascale — Naples
• Istituto Clinico Humanitas — Rozzano

Japan · 3 centers

• National Cancer Center Hospital East — Chiba
• Okayama University Hospital — Okayama
• The Cancer Institute Hospital of JFCR — Tokyo

Spain · 3 centers

• Hospital Universitario Vall d'Hebron — Barcelona
• Institut Catala d'Oncologia - L'Hospitalet — Barcelona
• South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez — Madrid

Australia · 2 centers

• The Alfred Hospital — Melbourne, VIC
• Linear Clinical Research — Nedlands

Denmark · 2 centers

• Aarhus University Hospital — Aarhus
• Center for Cancer and Organ Diseases - Rigshospitalet — Copenhagen

France · 2 centers

• CHU de Lille - Hopital Claude Huriez — Lille
• AP-HP Hopital Saint-Louis — Paris

Poland · 2 centers

• Pratia MCM Krakow — Krakow
• AIDPORT Sp. z o.o. — Skorzewo

South Korea · 2 centers

• Seoul National University Hospital — Seoul
• Asan Medical Center — Seoul

United Kingdom · 2 centers

• Leeds Teaching Hospitals NHS Trust — Leeds
• Oxford University Hospitals NHS Foundation Trust — Oxford

Identifiers

NCT: NCT07101328 · 27701 · 2025-524180-20-00 · J6N-MC-JUCA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗