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

NCT06667687 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: M24-8932024-512586-13-00
• Study Type: interventional
• Target: 165
• Locations: 5 countries
• Sites: 14

Brief Summary

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.

Conditions

Non-Hodgkin's Lymphoma

Keywords

Non-Hodgkin's Lymphomas; Diffuse Large B-Cell Lymphoma; Mantle Cell Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma; Waldenstroms Macrogloulinemia; Germinal Center B-cell; Activated B-Cell; NHL; DLBCL; MCL; FL; MZL; WM; GCB; ABC; Cancer; ABBV-291

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (7)

• Duration of Response (DOR) as Assessed by Investigator

  Up to 74 Months

• Progression-Free Survival (PFS) as Assessed by Investigator

  Up to 74 Months

• Time to response (TTR)

  Up to 74 Months

• Area Under the Curve (AUC) of ABBV-291

  Up to 12 Months

• Maximum Observed Plasma/Serum Concentration (Cmax) of ABBV-291

  Up to 12 Months

Study Arms (6)

Escalation: Non-Hodgkin Lymphoma (NHL) ABBV-291

EXPERIMENTAL

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

Expansion: Diffuse Large B-Cell Lymphoma (DLBCL) ABBV-291

EXPERIMENTAL

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

Expansion: Follicular Lymphoma (FL) ABBV-291

EXPERIMENTAL

Participants with R/R FL will receive the RP1ED of ABBV-291, as part of the 74 month study duration.

Drug: ABBV-291

Optimization: Mantle Cell Lymphoma (MCL) ABBV-291 Dose A

EXPERIMENTAL

Participants with R/R MCL will receive the dose A of ABBV-291, as part of the 74 month study duration.

Drug: ABBV-291

Optimization: MCL ABBV-291 Dose B

EXPERIMENTAL

Participants with R/R MCL will receive the dose B of ABBV-291, as part of the 74 month study duration.

Drug: ABBV-291

Optimization: MCL ABBV-291 Dose C

EXPERIMENTAL

Participants with R/R MCL will receive the dose C of ABBV-291, as part of the 74 month study duration.

Drug: ABBV-291

Interventions

ABBV-291 DRUG

Intravenous Infusion

Escalation: Non-Hodgkin Lymphoma (NHL) ABBV-291; Expansion: Diffuse Large B-Cell Lymphoma (DLBCL) ABBV-291; Expansion: Follicular Lymphoma (FL) ABBV-291; Optimization: MCL ABBV-291 Dose B; Optimization: MCL ABBV-291 Dose C; Optimization: Mantle Cell Lymphoma (MCL) ABBV-291 Dose A

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (14)

Carolina BioOncology Institute /ID# 265259

Huntersville, North Carolina, 28078, United States

COMPLETED

Willamette Valley Cancer Institute and Research Center /ID# 270945

Eugene, Oregon, 97401, United States

RECRUITING

Texas Oncology - Central/South Texas /ID# 270946

Austin, Texas, 78705, United States

RECRUITING

START Mountain Region /ID# 267592

West Valley City, Utah, 84119-3602, United States

COMPLETED

Virginia Cancer Specialists - Fairfax /ID# 265082

Fairfax, Virginia, 22031, United States

COMPLETED

St Vincent's Hospital Melbourne /ID# 261664

Fitzroy Melbourne, Victoria, 3065, Australia

RECRUITING

Sir Charles Gairdner Hospital /ID# 268579

Nedlands, Western Australia, 6009, Australia

RECRUITING

Hadassah Medical Center-Hebrew University /ID# 261658

Jerusalem, Jerusalem, 91120, Israel

RECRUITING

Tel Aviv Sourasky Medical Center /ID# 261659

Tel Aviv, Tel Aviv, 6423906, Israel

RECRUITING

Aichi Cancer Center /ID# 267471

Nagoya, Aichi-ken, 464-8681, Japan

RECRUITING

National Cancer Center Hospital East /ID# 261775

Kashiwa-shi, Chiba, 277-8577, Japan

RECRUITING

The Cancer Institute Hospital Of JFCR /ID# 267470

Koto-ku, Tokyo, 135-8550, Japan

RECRUITING

The Christie /ID# 267177

Manchester, M20 4BX, United Kingdom

RECRUITING

University Hospitals Plymouth NHS Trust /ID# 267174

Plymouth, PL6 5FP, United Kingdom

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Central Study Contacts

ABBVIE CALL CENTER

CONTACT

844-663-3742; abbvieclinicaltrials@abbvie.com

Study Design

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

Study Record Dates

• First Submitted: October 30, 2024
• First Posted: October 31, 2024
• Study Start: January 16, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): November 1, 2031
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); JP (3); US (5); GB (2); IL (2)