Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies

First-in-Human Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of the BTK Degrader, ABBV-101, in Participants With B-cell Malignancies

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, pharmacokinetics, and preliminary efficacy of ABBV-101 in adult participants in relapsed or refractory (R/R) non-Hodgkin's lymphomas: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large b-cell lymphoma (DLBCL), non-germinal center B cell (GCB) DLBCL, mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), or transformed indolent NHL. Adverse events will be assessed.

ABBV-101 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-101. Dose expansion part 2A will follow to further determine the safety and change in disease activity in participants with first line treatment (1L[non-US only]), second line or later of treatment (2L)+ CLL/SLL or third line or later of treatment (3L+) non-GCB DLBCL receiving ABBV-101 alone. Dose expansion Part 2B (non-US only) will follow to determine the safety and change in disease activity in participants with 1L or 2L+ CLL/SLL receiving ABBV-101 in combination with oral venetoclax. Approximately 390 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 oral doses of ABBV-101, until the MAD/MTD is determined, as part of the approximately 100 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101 alone or oral ABBV-101 at a dose determined in the dose escalation phase in combination with oral venetoclax, as part of the approximately 100 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hematologic Cancer
• Intervention / Treatment: Drug: Venetoclax; Drug: ABBV-101

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network_Princess Margaret Cancer Centre /ID# 253483
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM Notre-Dame Hospital /ID# 253428
• France
  • Paris, France, 75010
    • Hopital Saint-Louis /ID# 253663
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • Institut Bergonie /ID# 253664
  • Herault
    • Montpellier, Herault, France, 34295
      • CHU Montpellier - Hopital Saint Eloi /ID# 253666
  • Nord
    • Lille, Nord, France, 59037
      • CHRU Lille - Hopital Claude Huriez /ID# 253665
  • Pays de la Loire Region
    • Nantes, Pays de la Loire Region, France, 44000
      • Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 256248
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
      • Institut Gustave Roussy /ID# 253662
• Germany
  • Berlin, Germany, 12203
    • Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 257431
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf /ID# 264566
  • Baden-Wurttemberg
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Universitaetsklinikum Ulm /ID# 253742
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Universitaetsklinikum Wuerzburg /ID# 254636
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, 18057
      • Universitaetsmedizin Rostock /ID# 259657
  • Saarland
    • Homburg, Saarland, Germany, 66424
      • Universitaetsklinikum des Saarlandes /ID# 257435
• Israel
  • Central District
    • Ẕerifin, Central District, Israel, 70300
      • Yitzhak Shamir Medical Center /ID# 254566
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91120
      • Hadassah Medical Center-Hebrew University /ID# 251123
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 251122
    • Tel Aviv, Tel Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 259608
• Italy
  • Bergamo, Italy, 24127
    • ASST Papa Giovanni XXIII /ID# 260317
  • Bologna, Italy, 40138
    • IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 255172
  • Milano
    • Milan, Milano, Italy, 20132
      • IRCCS Ospedale San Raffaele /ID# 253531
    • Milan, Milano, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda /ID# 253532
  • Piedmont
    • Turin, Piedmont, Italy, 10126
      • A.O.U. CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO - Ospedale Molinette /ID# 253530
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 250684
  • Kyoto
    • Kyoto, Kyoto, Japan, 606-8507
      • Kyoto University Hospital /ID# 261837
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 250680
    • Koto-ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital Of JFCR /ID# 260375
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall de Hebron /ID# 260447
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal /ID# 260450
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz /ID# 253654
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro /ID# 253655
  • Salamanca, Spain, 37711
    • Hospital Universitario de Salamanca /ID# 253656
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro - Majadahonda /ID# 260196
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
      • Addenbrookes Hospital /ID# 256242
  • England
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary /ID# 255171
  • Greater London
    • London, Greater London, United Kingdom, NW1 2BU
      • University College London Hospital /ID# 260202
    • London, Greater London, United Kingdom, SE5 9RS
      • Kings College Hospital NHS Foundation Trust /ID# 253670
• United States
  • Arizona
    • Tempe, Arizona, United States, 85284-1812
      • Arizona Oncology Associates, PC-HOPE /ID# 252351
  • California
    • Orange, California, United States, 92868-3201
      • UC Irvine Medical Center /ID# 263020
    • Palo Alto, California, United States, 94304
      • Stanford University - Palo Alto /ID# 249683
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers - Lone Tree /ID# 252237
  • Illinois
    • Chicago, Illinois, United States, 60611-2927
      • Northwestern University Feinberg School of Medicine /ID# 249347
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5400
      • Beth Israel Deaconess Medical Center /ID# 249302
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey /ID# 249323
  • New York
    • Albany, New York, United States, 12206-5013
      • New York Oncology Hematology - Albany Cancer Center /ID# 252240
    • Lake Success, New York, United States, 11042
      • Northwell Health - Monter Cancer Center /ID# 250422
    • Rochester, New York, United States, 14642-0001
      • University of Rochester Medical Center /ID# 249324
  • Ohio
    • Cincinnati, Ohio, United States, 45267-2800
      • UC Health - Cincinnati /ID# 249299
  • Oregon
    • Eugene, Oregon, United States, 97401-6036
      • Oncology Assoc. of Oregon PC - WVCI and Research Ctr - Springfield /ID# 249309
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania /ID# 250341
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center /ID# 249293

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• For Dose Escalation (Part 1) only (including backfill): Participants have received at least two prior systemic therapies, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), have measurable disease requiring treatment, and have a documented diagnosis for one of the following third line or later B-cell malignancies, from one of the following world health organization (WHO)-defined histologies (Swerdlow et al 2016):

  • Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)

    1. For Dose Escalation (Part 1) backfill only - Bruton's tyrosine kinase inhibitor (BTKi)/Bruton's tyrosine kinase degrader (BTKd)-naïve CLL/SLL. Participants with a documented diagnosis of CLL/SLL who have received at least one prior systemic therapy that cannot be a BTK inhibitor or degrader, and, with the exception of BTK pathway agents, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), and have measurable disease requiring treatment.
    2. For Dose Escalation (Part 1) backfill only - BTKi/BCL-2i combination regimen-exposed 2L CLL/SLL. Participants with a documented diagnosis of CLL/SLL who have received one prior systemic therapy with a BTKi and BCL-2i combination regimen, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), and have measurable disease requiring treatment.
  • Chimeric antigen receptor T-cells (CAR-T)/hematopoietic cell transplant (HCT) relapsed/refractory (R/R) or ineligible diffuse large b-cell lymphoma (DLBCL) from the following histologies: DLBCL not otherwise specified (NOS) (germinal center B cell [GCB] and non-GCB DLBCL), T-cell/histiocyte-rich large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, anaplastic lymphoma kinase positive (ALK+) large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma NOS.
  • Mantle cell lymphoma (MCL)
  • Follicular lymphoma [FL] (grades 1-3b)
  • Marginal zone lymphoma [MZL] (splenic, extranodal, and nodal)
  • Waldenström macroglobulinemia (WM)
  • Transformed indolent non-Hodgkin's lymphoma (iNHL)
• For Dose Expansion (Part 2a) CLL/SLL only: Participants with a documented diagnosis of CLL/SLL in their first-line or later treatment.
• For Dose Expansion (Part 2a) DLBCL only: Participants have received at least two prior systemic therapies, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), have measurable disease requiring treatment, and have documented diagnosis of CAR-T/HCT R/R or ineligible non-GCB DLBCL who are in their third line or later treatment with histology based on criteria established by the WHO.
• For Dose Exploration of ABBV-101 combination with venetoclax (Part 2b) CLL/SLL only: Participants with a documented diagnosis of CLL/SLL in their first-line or later treatment: In safety lead-in for each dose level, participants must have received at least one prior systemic therapy.
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2. For EU only: Participant has an ECOG PS of 0 or 1.
• Participant has a life expectancy >= 12 weeks.
• Prior Bruton's tyrosine kinase inhibitor (BTKi) is allowed.
• Adequate hematologic, renal, and hepatic function per the protocol.

Exclusion Criteria:

• Previously treated with a Bruton's tyrosine kinase (BTK) degrader.
• Known active central nervous system (CNS) disease, or primary CNS lymphoma. Participants with prior CNS disease that have been effectively treated may be eligible.
• Uncontrolled active systemic infection requiring systemic treatment that is ongoing or was completed <= 14 days before the first dose of study drug, or active cytomegalovirus infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation ABBV-101; Participants with relapsed or refractory (R/R) Non-Hodgkin's lymphoma (NHL) will receive escalating doses of ABBV-101, until the maximum administered dose (MAD)/Maximum tolerated dose (MTD) is determined, as part of the approximately 100 month study duration.	Drug: ABBV-101; Oral:Tablet
Experimental: Part 2A: Dose Expansion ABBV-101 R/R & Treatment-Naive CLL/SLL; Participants with R/R and treatment-naive chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL) will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 100 month study duration.	Drug: ABBV-101; Oral:Tablet
Experimental: Part 2A: Dose Expansion ABBV-101 R/R non-GCB DLBCL; Participants with R/R non-germinal center B cell (GCB) diffuse large B-cell lymphoma (DLBCL) will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 100 month study duration.	Drug: ABBV-101; Oral:Tablet
Experimental: Part 2B: Dose Expansion ABBV-101 + Venetoclax in CLL/SLL; Participants with R/R and treatment-naive CLL/SLL will receive ABBV-101 at the dose determined in the dose escalation arm in combination with venetoclax, as part of the approximately 100 month study duration.	Drug: Venetoclax; Oral; Drug: ABBV-101; Oral:Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Laboratory Parameters	Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.	Up to Approximately Two Years
Change in Vital Signs	Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.	Up to Approximately Two Years
Change in Electrocardiogram (ECG)	12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.	Up to Approximately Two Years
Number of Participants with Adverse Events (AE)	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 Approximately 100 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of ABBV-101	Maximum observed serum concentration of ABBV-101.	Up to Approximately One Year
Time to Cmax (Tmax) of ABBV-101	Time to Cmax of ABBV-101.	Up to Approximately One Year
Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-101	Area under the serum concentration versus time curve (AUC) of ABBV-101.	Up to Approximately One Year
Duration of Response (DOR)	DOR is defined for participants achieving PR or better as the time from the initial response per Investigator review to disease progression or death of any cause, whichever occurs earlier.	Up to Approximately Two Years
Number of Participants with Response of Partial Response (PR) or Better Response (Overall Response) per Disease-Specific Criteria	Number of participants with response of PR or better response (overall response) per disease-specific criteria.	Up to Approximately Two Years
Maximum Observed Serum Concentration (Cmax) of Venetoclax	Maximum observed serum concentration of venetoclax.	Up to Approximately One Year
Time to Cmax (Tmax) of Venetoclax	Time to Cmax of venetoclax.	Up to Approximately One Year
Area Under the Serum Concentration Versus Time Curve (AUC) of Venetoclax	Area under the serum concentration versus time curve (AUC) of venetoclax.	Up to Approximately One Year

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related info

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2023
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): March 1, 2031

Study Registration Dates

• First Submitted: February 22, 2023
• First Submitted That Met QC Criteria: February 22, 2023
• First Posted (Actual): March 3, 2023

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Follicular lymphoma (FL); Chronic lymphocytic leukemia (CLL); Small lymphocytic lymphoma (SLL); Hematopoietic cell transplant (HCT); Mantle cell lymphoma (MCL); Marginal zone lymphoma (MZL); Hematologic Cancer; Chimeric antigen receptor T-cells (CAR-T); Waldenström macroglobulinemia (WM); Transformed Indolent non-Hodgkin's lymphoma (INHL); ABBV-101; Relapsed/refractory (R/R) or ineligible Diffuse large B-cell lymphoma (DLBCL)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Hematologic Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone; venetoclax
• Other Study ID Numbers: M23-647; 2023-503594-38-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No