Clinical trial 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
Official title: A Phase 1 First-In-Human Study Evaluating Safety, Pharmacokinetics, and Efficacy of ABBV-291 in Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-10-31
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AE)s
timeFrame: Up to 74 Months
measure: Percentage of Participants with Dose Limiting Toxicities (DLT)s
timeFrame: Up to 74 Months
measure: Percentage of Participants with Clinically Significant Laboratory Values (Chemistry, and Hematology)
timeFrame: Up to 74 Months
measure: Percentage of Participants with Clinically Significant Vital Sign Measurements
timeFrame: Up to 74 Months
measure: Percentage of Participants with Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: Up to 74 Months
measure: Objective Response Rate (ORR)
timeFrame: Up to 74 Months
Secondary outcomes:
measure: Duration of Response (DOR) as Assessed by Investigator
timeFrame: Up to 74 Months
measure: Progression-Free Survival (PFS) as Assessed by Investigator
timeFrame: Up to 74 Months
measure: Time to response (TTR)
timeFrame: Up to 74 Months
measure: Area Under the Curve (AUC) of ABBV-291
timeFrame: Up to 12 Months
measure: Maximum Observed Plasma/Serum Concentration (Cmax) of ABBV-291
timeFrame: Up to 12 Months
measure: Time to Cmax (Tmax) of ABBV-291
timeFrame: Up to 12 Months
measure: Half-Life (t1/2) of ABBV-291
timeFrame: Up to 12 Months
Other outcomes:
Locations:
city: Huntersville
country: United States
facility: Carolina BioOncology Institute /ID# 265259
state: North Carolina
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center /ID# 270945
state: Oregon
city: Austin
country: United States
facility: Texas Oncology - Central/South Texas /ID# 270946
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region /ID# 267592
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists - Fairfax /ID# 265082
state: Virginia
city: Fitzroy Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne /ID# 261664
state: Victoria
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 261659
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 261658
state: Yerushalayim
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center /ID# 267471
state: Aichi
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital Of JFCR /ID# 267470
state: Tokyo
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: