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NCT Number: NCT06667687

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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

St Vincent's Hospital Melbourne /ID# 261664, Fitzroy Melbourne, Victoria, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ABBV-291

Drug

Intravenous Infusion

Primary outcomes

  1. Percentage of Participants with Adverse Events (AE)s

    Time frame: Up to 74 Months

    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.

  2. Percentage of Participants with Dose Limiting Toxicities (DLT)s

    Time frame: Up to 74 Months

    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.

  3. Percentage of Participants with Clinically Significant Laboratory Values (Chemistry, and Hematology)

    Time frame: Up to 74 Months

    Percentage of participants with clinically significant laboratory values (chemistry, and hematology).

  4. Percentage of Participants with Clinically Significant Vital Sign Measurements

    Time frame: Up to 74 Months

    Vital sign are defined as determinations of systolic and diastolic blood pressure, pulse rate, respiratory rate, and body temperature.

  5. Percentage of Participants with Clinically Significant Electrocardiogram (ECG) Findings

    Time frame: Up to 74 Months

    Percentage of participants with clinically significant ECG findings.

  6. Objective Response Rate (ORR)

    Time frame: Up to 74 Months

    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).

Secondary outcomes

  1. Duration of Response (DOR) as Assessed by Investigator

    Time frame: Up to 74 Months

    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.

  2. Progression-Free Survival (PFS) as Assessed by Investigator

    Time frame: Up to 74 Months

    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.

  3. Time to response (TTR)

    Time frame: Up to 74 Months

    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.

  4. Area Under the Curve (AUC) of ABBV-291

    Time frame: Up to 12 Months

    AUC is defined as the area under the plasma/serum concentration-time curve of ABBV-291.

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

    Time frame: Up to 12 Months

    Cmax is defined as maximum observed plasma/serum concentration of ABBV-291.

  6. Time to Cmax (Tmax) of ABBV-291

    Time frame: Up to 12 Months

    Tmax is defined as time to Cmax of ABBV-291.

  7. Half-Life (t1/2) of ABBV-291

    Time frame: Up to 12 Months

    t1/2 is defined as the half-life of ABBV-291.

Study contacts

Contact information is provided by the study sponsor or research team.

ABBVIE CALL CENTER

CONTACT

[email protected]

844-663-3742

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2031
First posted
Oct 31, 2024
Registry last updated
Jan 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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