A Study to Assess the Adverse Events, Change in Disease Activity, and How Intravenously Infused ABBV-319 Moves Through the Bodies of Adult Participants With Relapsed or Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), or Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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B-cell Lymphoma is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). Follicular Lymphoma is a slow-growing type of non-Hodgkin lymphoma. Chronic lymphocytic leukemia (CLL) is the most common leukemia (cancer of blood cells). The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of ABBV-319 in adult participants in relapsed or refractory (R/R) diffuse large b-cell lymphoma (DLBCL), R/R follicular lymphoma (FL), or R/R CLL. Adverse events will be assessed. ABBV-319 is an investigational drug being developed for the treatment of R/R DLBCL, R/R FL, or R/R CLL. This study will include a dose escalation phase to determine the recommended Phase 2 dose (RP2D) of ABBV-319 and a dose expansion phase to determine the change in disease activity in participants with R/R DLBCL, R/R FL, and R/R CLL. Approximately 114 adult participants with R/R B cell lymphomas including R/R DLBCL, R/R FL, and R/R CLL will be enrolled in the study in sites world wide. In the Dose Escalation phase of the study participants will receive escalating intravenously infused doses of ABBV-319 in 21-day cycles, until the recommended Phase 2 dose is determined. In the dose expansion phase of the study participants receive intravenously infused ABBV-319 in 21-day cycles. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Official Title
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A First In Human Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-319 in B-cell Malignancies

Conditions
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Diffuse Large B-Cell Lymphoma, Chronic Lymphocytic Leukemia, Follicular Lymphoma

Intervention / Treatment
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* Drug: ABBV-319


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For dose escalation (Part 1) only: Participants with documented diagnosis of B-cell malignancies including those with histology based on criteria established by the World Health Organization (WHO), and measurable disease requiring treatment, as per the protocol. For the relapsed or refractory diffuse large b-cell lymphoma (DLBCL), follicular lymphoma (FL), and Chronic lymphocytic leukemia (CLL) dose expansion cohorts (Part 2) only: Participants with documented diagnosis of one of the B-cell malignancies noted in the protocol with histology based on criteria established by the WHO, and measurable disease requiring treatment, as per the protocol. Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Laboratory values meeting the criteria noted in the protocol. For participants previously treated with a CD19-targeting therapy (eg, CD19 monoclonal antibody) a core or excision tumor biopsy subsequent to the most recent CD19-targeting therapy must be collected. Participant must have measurable disease, as defined by the 2014 Lugano Classification. Exclusion Criteria: Known active central nervous system (CNS) disease, or primary CNS lymphoma. Know active infection or clinically significant uncontrolled conditions as per the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation ABBV-319<br>Participants with relapsed or refractory (R/R) B cell lymphomas including diffuse large b-cell lymphoma (DLBCL) or follicular lymphoma (FL), and Chronic lymphocytic leukemia (CLL) will receive escalating doses of ABBV-319 in 21-day cycles, until the recommended Phase 2 dose (RP2D) is determined. | Drug: ABBV-319<br>* Intravenous (IV); Infusion<br>|
| Experimental: (ABBV-319) Diffuse Large B-cell Lymphoma (DLBCL) Participants<br>Participants with R/R DLBCL will receive ABBV-319 in 21-day cycles. | Drug: ABBV-319<br>* Intravenous (IV); Infusion<br>|
| Experimental: (ABBV-319) Follicular Lymphoma (FL) Participants<br>Participants with R/R FL will receive ABBV-319 in 21-day cycles. | Drug: ABBV-319<br>* Intravenous (IV); Infusion<br>|
| Experimental: (ABBV-319) Chronic Lymphocytic Leukemia (CLL) Participants<br>Participants with R/R CLL will receive ABBV-319 in 21-day cycles. | Drug: ABBV-319<br>* Intravenous (IV); Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Dose-Limiting Toxicities (DLT) | A DLT is defined as any adverse event (AE) for which a clear alternative cause cannot be established (eg, attributed to the disease under study, another disease, or to a concomitant medication by the study investigators or medical monitor). | Day 21 | 
| Number of Participants with Adverse Events (AE) | AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. | Up to 30 Months | 
| Maximum Observed Serum Concentration (Cmax) of ABBV-319 | Maximum observed serum concentration of ABBV-319. | Up to 6 Months | 
| Time to Cmax (Tmax) of ABBV-319 | Time to Cmax of ABBV-319. | Up to 6 Months | 
| Terminal Phase Elimination Half-Life (t1/2) of ABBV-319 | Terminal phase elimination half-life of ABBV-319. | Up to 6 Months | 
| Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-319 | Area under the serum concentration versus time curve (AUC) of ABBV-319. | Up to 6 Months | 
| Antidrug Antibody (ADA) | Incidence and concentration of anti-drug antibodies. | Up to 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Response of Partial Response (PR) or Better per Disease-Specific Criteria | Number of participants with response of PR or better per disease-specific criteria. | Up to 6 Months | 
| Duration of Response (DOR) | DOR is defined for participants achieving a complete response (CR)/PR as the time from the initial response per investigator review to disease progression or death of any cause, whichever occurs earlier. | Up to 6 Months | 
| Time to Response | Time to response is defined for participants achieving a CR/PR as the time from starting therapy to first a CR/PR. | Up to 6 Months | 
| Progression Free Survival (PFS) Time | PFS is defined as time from first study treatment to a documented disease progression as determined by the investigator, or death due to any cause, whichever occurs earlier. | Up to 30 Months | 
| Overall survival (OS) Time | OS is defined as time from first study treatment to death due to any cause. | Up to 30 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diffuse Large B-Cell Lymphoma, Chronic Lymphocytic Leukemia, Follicular Lymphoma, Cancer, B-Cell Malignancies, ABBV-319