Study to Evaluate Adverse Events, Change in Disease Activity, and How Intravenously Infused ABBV-291 Moves Through the Body in Adult Participants With Non-Hodgkin's Lymphoma

A Phase 1 First-In-Human Study Evaluating Safety, Pharmacokinetics, and Efficacy of ABBV 291 in Non-Hodgkin's Lymphoma

Non-Hodgkin's lymphoma (NHL) is a cancer that arises from the transformation of normal B and T lymphocytes (white blood cells). The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of ABBV-291 in adult participants in relapsed or refractory (R/R) NHL, including but not limited to diffuse large b-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). Adverse events will be assessed.

ABBV-291 is an investigational drug being developed for the treatment of NHL. This study will include a dose escalation phase to determine the maximum administered dose (MAD)/Maximum tolerated dose (MTD) of ABBV-291 and a dose expansion/optimization phase to determine the change in disease activity in participants with R/R NHL. Approximately 165 adult participants with multiple NHL subtypes will be enrolled in the study in sites world wide

In the dose escalation phase of the study participants will receive escalating Intravenously (IV) infused doses of ABBV-291, until the MAD/MTD is determined. In the dose expansion/optimization phase of the study participants receive IV infused ABBV-291, as part of the approximately 74 month study duration.

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, and side effects.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: ABBV-291

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Fitzroy Melbourne, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne /ID# 261664
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital /ID# 268579
• Israel
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91120
      • Hadassah Medical Center-Hebrew University /ID# 261658
  • Tel Aviv
    • Tel Aviv, Tel Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 261659
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Aichi Cancer Center /ID# 267471
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 261775
  • Tokyo
    • Koto-ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital Of JFCR /ID# 267470
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie /ID# 267177
  • Plymouth, United Kingdom, PL6 5FP
    • University Hospitals Plymouth NHS Trust /ID# 267174
• United States
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute /ID# 265259
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center /ID# 270945
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology - Central/South Texas /ID# 270946
  • Utah
    • West Valley City, Utah, United States, 84119-3602
      • START Mountain Region /ID# 267592
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists - Fairfax /ID# 265082

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• For dose escalation (Part 1) only: Participants must have documented diagnosis of B-cell malignancies including (but not limited to) the following, with histology based on criteria established by the World Health Organization (WHO), and measurable disease requiring treatment:

  • Mantle cell lymphoma (MCL);
  • Marginal zone lymphoma (MZL);
  • Waldenstrom macroglobulinemia (WM);
  • Diffuse large b-cell lymphoma (DLBCL) (including: germinal center B-cell type, activated B-cell type, primary cutaneous DLBCL [leg type], Epstein-Barr virus-positive (EBV+) DLBCL [not otherwise specified], DLBCL associated with chronic inflammation, human herpesvirus 8-positive [HHV8+] DLBCL [not otherwise specified], B cell lymphoma [unclassifiable] with features intermediate between DLBCL and classical Hodgkin lymphoma, high-grade B-cell lymphoma [not otherwise specified], high-grade B-cell lymphoma [with MYC (avian myelocytomatosis viral oncogene homolog) and BCL2 and/or BCL6 rearrangements], DLBCL arising from follicular lymphoma [FL] [transformed FL]);
  • FL Grades 1 to 3B;

• For dose expansion (Part 2) only: Participants must have documented diagnosis of one of the following B-cell malignancies, with histology based on criteria established by the WHO, and measurable disease requiring treatment:

  • Part 2a only: DLBCL (including: germinal center B-cell type, activated B-cell type, primary cutaneous DLBCL [leg type], EBV+ DLBCL [not otherwise specified], DLBCL associated with chronic inflammation, HHV8+ DLBCL [not otherwise specified], B-cell lymphoma [unclassifiable] with features intermediate between DLBCL and classical Hodgkin lymphoma, high-grade B-cell lymphoma [not otherwise specified], high-grade B-cell lymphoma [with MYC and BCL2 and/or BCL6 rearrangements], DLBCL arising from FL [transformed FL]);
  • Part 2b only: FL Grades 1 to 3B;
  • Part 2c only: Mantle cell lymphoma;

• For all participants (Parts 1 and 2):

  • Must be considered relapsed or refractory to, or intolerant of, at least 2 or more prior lines of therapy known to provide a clinical benefit for their condition, and for whom there is no appropriate locally available therapy known to provide clinical benefit (e.g., standard chemotherapy or autologous stem cell transplantation [ASCT]).
  • Indolent non-Hodkin's lymphoma (NHL) participants must meet relevant disease specific requirements for treatment (e.g., National Comprehensive Cancer Network [NCCN], Groupe d'Etude des Lymphomes Folliculaires [GELF]).
  • History of allogeneic stem cell transplantation must be stable off of immunosuppression for at least 3 months.
  • For participants enrolled in backfill cohorts or at dose levels previously cleared, subjects must provide consent to an on-treatment fresh tumor biopsy from the same tumor lesion as the baseline tumor tissue. This requirement may be waived at the discretion of the contract research organization (CRO) Medical Monitor if collecting a biopsy would place the subject at risk of harm or would require a technically complicated procedure based on tumor location as assessed by the investigator or could hinder a subject's ability to participate in the study.

  • Previously treated with a CD79b-targeting therapy (e.g., CD79b monoclonal antibody) a core or excision tumor biopsy subsequent to the most recent CD79b-targeting therapy must be collected. Tumor biopsy requirements may be modified by Sponsor during the study. This requirement may be waived at the discretion of the contract research organization (CRO) Medical Monitor if collecting a biopsy would place the subject at risk of harm or would require a technically complicated procedure based on tumor location as assessed by the investigator or could hinder a subject's ability to participate in the study.

    • CD79b expression status will be assessed in all participants.
• Have an eastern cooperative oncology group (ECOG) Performance Status of 0 or 1.
• Laboratory values meeting the criteria in the protocol within the screening period prior to the first dose of study drug (if multiple samples are drawn within the screening period, the sample/result immediately prior to Cycle 1 Day 1 is applicable).
• Availability of representative baseline tumor tissue (most recent archived tumor tissue or fresh biopsy collected during screening phase) suitable for immunohistochemistry (IHC) testing. This requirement may be waived at the discretion of the CRO Medical Monitor if collecting a biopsy at screening would place the participant at risk of harm or would require a technically complicated procedure based on tumor location as assessed by the investigator or could hinder a participant's ability to participate in the study.

Exclusion Criteria:

• History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or pneumonitis.

• Treatment with any of the following:

  • Anticancer therapy including chemotherapy, radiotherapy, small molecule, investigational, and biologic agents within 14 days (or at least 5 half-lives, whichever is shorter), prior to the first dose of the study treatment;
  • CD79b-directed agents (e.g., CD79b monoclonal antibody therapy) within 4 weeks (or at least 5 half-lives, whichever is shorter) prior to the first dose of study treatment.
  • Prior treatment with an antibody drug conjugate that consists of a topoisomerase I inhibitor.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escalation: Non-Hodgkin Lymphoma (NHL) ABBV-291; Participants with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), except chronic lymphocytic leukemia (CLL), will receive escalating doses of ABBV-291, as part of the 74 month study duration.	Drug: ABBV-291; Intravenous Infusion
Experimental: Expansion: Diffuse Large B-Cell Lymphoma (DLBCL) ABBV-291; Participants with R/R DLBCL will receive the recommended Phase 1 expansion dose (RP1ED) of ABBV-291, as part of the 74 month study duration.	Drug: ABBV-291; Intravenous Infusion
Experimental: Expansion: Follicular Lymphoma (FL) ABBV-291; Participants with R/R FL will receive the RP1ED of ABBV-291, as part of the 74 month study duration.	Drug: ABBV-291; Intravenous Infusion
Experimental: Optimization: Mantle Cell Lymphoma (MCL) ABBV-291 Dose A; Participants with R/R MCL will receive the dose A of ABBV-291, as part of the 74 month study duration.	Drug: ABBV-291; Intravenous Infusion
Experimental: Optimization: MCL ABBV-291 Dose B; Participants with R/R MCL will receive the dose B of ABBV-291, as part of the 74 month study duration.	Drug: ABBV-291; Intravenous Infusion
Experimental: Optimization: MCL ABBV-291 Dose C; Participants with R/R MCL will receive the dose C of ABBV-291, as part of the 74 month study duration.	Drug: ABBV-291; Intravenous Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Adverse Events (AE)s	An 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 74 Months
Percentage of Participants with Dose Limiting Toxicities (DLT)s	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.	Up to 74 Months
Percentage of Participants with Clinically Significant Laboratory Values (Chemistry, and Hematology)	Percentage of participants with clinically significant laboratory values (chemistry, and hematology).	Up to 74 Months
Percentage of Participants with Clinically Significant Vital Sign Measurements	Vital sign are defined as determinations of systolic and diastolic blood pressure, pulse rate, respiratory rate, and body temperature.	Up to 74 Months
Percentage of Participants with Clinically Significant Electrocardiogram (ECG) Findings	Percentage of participants with clinically significant ECG findings.	Up to 74 Months
Objective Response Rate (ORR)	ORR is defined as the percentage of participants with a confirmed best overall response (BOR) of partial response (PR) or better per disease-specific response criteria (e.g., Lugano classification).	Up to 74 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) as Assessed by Investigator	DOR is defined for participants achieving a confirmed PR or better as the time from the initial response of PR (or better) per investigator review according to disease-specific response criteria to disease progression or death of any cause, whichever occurs earlier.	Up to 74 Months
Progression-Free Survival (PFS) as Assessed by Investigator	PFS is defined as time from first study treatment to a documented disease progression according to disease-specific response criteria, as determined by the investigator, or death due to any cause, whichever occurs earlier.	Up to 74 Months
Time to response (TTR)	TTR is defined as time from first study treatment to the initial response of PR (or better) per investigator review according to disease-specific response criteria.	Up to 74 Months
Area Under the Curve (AUC) of ABBV-291	AUC is defined as the area under the plasma/serum concentration-time curve of ABBV-291.	Up to 12 Months
Maximum Observed Plasma/Serum Concentration (Cmax) of ABBV-291	Cmax is defined as maximum observed plasma/serum concentration of ABBV-291.	Up to 12 Months
Time to Cmax (Tmax) of ABBV-291	Tmax is defined as time to Cmax of ABBV-291.	Up to 12 Months
Half-Life (t1/2) of ABBV-291	t1/2 is defined as the half-life of ABBV-291.	Up to 12 Months

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Actual): October 31, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: August 13, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; DLBCL; NHL; Follicular Lymphoma; Marginal Zone Lymphoma; FL; MCL; MZL; Mantle Cell Lymphoma; Diffuse Large B-Cell Lymphoma; ABC; WM; GCB; Non-Hodgkin's Lymphomas; Activated B-Cell; Waldenstroms Macrogloulinemia; Germinal Center B-cell; ABBV-291
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone
• Other Study ID Numbers: M24-893; 2024-512586-13-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes