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.
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]);
History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or pneumonitis.
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.
Sequential
ABBV-291
DrugIntravenous Infusion
6
Treatment groupsSee each treatment group below.
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.
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.
Percentage of Participants with Clinically Significant Laboratory Values (Chemistry, and Hematology)
Percentage of participants with clinically significant laboratory values (chemistry, and hematology).
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.
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.
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.
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.
Area Under the Curve (AUC) of ABBV-291
AUC is defined as the area under the plasma/serum concentration-time curve of ABBV-291.
