A Study of LY4152199 in Participants With Previously Treated B-cell Cancers and Leukemia
- Conditions
- Leukemia, Lymphocytic, Chronic, B-CellLymphoma, B-cell Marginal ZoneLymphoma, Non-HodgkinB-cell LymphomaWaldenstrom MacroglobulinemiaLymphoma, Mantle-CellLymphoma, Large B-Cell, DiffuseBurkitt LymphomaLymphoma, FollicularLeukemia, B-Cell
- Interventions
- Drug: LY4152199 - IVDrug: LY4152199 - SC
- Registration Number
- NCT07101328
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 295
-
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1A: Dose Escalation (Cohort A) LY4152199 - IV Escalating doses of LY4152199 administered intravenously (IV) or subcutaneously (SC) Phase 1A: Dose Escalation (Cohort A) LY4152199 - SC Escalating doses of LY4152199 administered intravenously (IV) or subcutaneously (SC) Phase 1A: Dose Optimization (Cohort B) LY4152199 - SC Two or more doses of LY4152199 (evaluated during dose escalation) administered SC Phase 1B: Dose Expansion (Cohort C) LY4152199 - SC LY4152199 administered SC
- Primary Outcome Measures
Name Time Method Phase 1a - Number of Participants with Dose Limiting Toxicities of LY4152199 Cycle 1 (28 days) Phase 1b - Overall Response Rate (ORR): Percentage of Participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) 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 or death due to any cause, whichever occurs first
- Secondary Outcome Measures
Name Time Method Phase 1a and 1b - Pharmacokinetics (PK): Area under the Concentration versus Time Curve (AUC) of LY4152199 Baseline up to approximately 91 weeks Phase 1a and 1b - PK: Maximum Concentration (Cmax) of LY4152199 Baseline up to approximately 91 weeks Phase 1a - Overall Response Rate (ORR): Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) 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 or death due to any cause, whichever occurs first
Phase 1a and Ib - Duration of Response (DOR) Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy Time between the date of first documented response (CR or PR) to the date of first disease progression or death due to any cause, whichever occurs first
Phase 1a and Ib - Time to Response (TTR) 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 (CR or PR)
Phase 1a and Ib - Progression Free Survival (PFS) 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
Phase 1a and Ib - Disease Control Rate (DCR) Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy Percentage of efficacy-evaluable participants who achieved a BOR of CR, PR, or stable disease