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

Study Identifier:
M24-893
CT.gov Identifier:
NCT06667687
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
2024-512586-13-00
Study Contact Information:
N/A
Recruiting

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Study Summary

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.

To evaluate the safety, pharmacokinetics (PK), and efficacy of ABBV-291 monotherapy in pts with R/R B-NHL.

Safety evaluations include AE monitoring, DLTs, vital signs, ECG, and clinical laboratory parameters. Response evaluations are performed per disease-specific response criteria and include objective response rate, duration of response, and progression-free survival. PK parameters are determined using noncompartmental methods.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Lymphoma
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Escalation
    • Read More
  • Drug: Drug: ABBV-291
  • Drug: Experimental: Expansion: Diffuse Large B-Cell Lymphoma (DLBCL) ABBV-291
  • Drug: Experimental: Expansion: Follicular Lymphoma (FL) ABBV-291
  • Drug: Experimental: Optimization: Mantle Cell Lymphoma (MCL) ABBV-291 Dose A
  • Drug: Experimental: Optimization: MCL ABBV-291 Dose B
  • Drug: Experimental: Optimization: MCL ABBV-291 Dose C
  • Drug: The study consists of 2 parts: dose escalation (up to 45 pts), and dose expansion and optimization (120 pts). ABBV-291 is administered intravenously. In the BOIN-guided dose-escalation, ABBV-291 administration for the first 2 pts is staggered by ≥ 24 h at the first 2 dose levels (DLs); dose-limiting toxicities (DLTs) are assessed for 35 days from the initial dose. In dose expansion, ABBV-291 is evaluated at the RP1ED in DLBCL and FL; for dose optimization, ABBV-291 is evaluated in ≥ 2 DLs in MCL. Pts continue treatment until disease progression, intolerable toxicity, or other study discontinuation criteria are met.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    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.
    • Pts (≥ 18 years) who have a documented diagnosis of B-NHL (except chronic lymphocytic leukemia), measurable disease, ECOG 0–1, and are R/R to or intolerant of ≥ 2 prior lines of therapy, with no other available therapies of clinical benefit.
    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.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Status
    Will Be Recruiting
    Condition(s) Treated at Site
    Lymphoma