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: third line or later of treatment (3L) + 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 and a dose expansion phase to determine the change in disease activity in participants with CLL or non-GCB DLBCL. Approximately 128 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 60 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101, as part of the approximately 60 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: Recruiting
• Conditions: Hematologic Cancer
• Intervention / Treatment: Drug: ABBV-101

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Israel
  • HaMerkaz
    • Zerifin, HaMerkaz, Israel, 70300
      • Recruiting
      • Assaf Harofeh Medical Center /ID# 254566
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • Recruiting
      • The Chaim Sheba Medical Center /ID# 251122
    • Tel Aviv, Tel-Aviv, Israel, 6423906
      • Recruiting
      • Tel Aviv Sourasky Medical Center /ID# 259608
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 91120
      • Recruiting
      • Hadassah Medical Center-Hebrew University /ID# 251123
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East /ID# 250684
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 606-8507
      • Recruiting
      • Kyoto University Hospital /ID# 261837
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital /ID# 250680
    • Koto-ku, Tokyo, Japan, 135-8550
      • Recruiting
      • The Cancer Institute Hospital Of JFCR /ID# 260375
• United States
  • Arizona
    • Tempe, Arizona, United States, 85284-1812
      • Recruiting
      • Arizona Oncology Associates, PC-HOPE /ID# 252351
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Recruiting
      • Rocky Mountain Cancer Centers /ID# 252237
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey /ID# 249323
  • New York
    • Albany, New York, United States, 12206-5013
      • Recruiting
      • New York Oncology Hematology - Albany Cancer Center /ID# 252240
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Northwell Health - Monter Cancer Center /ID# 250422
    • Rochester, New York, United States, 14642-0001
      • Recruiting
      • University of Rochester Medical Center /ID# 249324
  • Oregon
    • Eugene, Oregon, United States, 97401-6036
      • Recruiting
      • Oncology Assoc. of Oregon PC - WVCI and Research Ctr - Springfield /ID# 249309
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania /ID# 250341
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • 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: Participants with documented diagnosis for one of the following 3L+ B-cell malignancies, from one of the following WHO-defined histologies (Swerdlow et al 2016):

  • Chronic lymphocytic leukemia (CLL)
  • Small lymphocytic lymphoma (SLL)
  • 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 2) only: Participants with documented diagnosis of CLL who are 3L+ including those with Bruton's tyrosine kinase (BTK) mutations or CAR-T/HCT R/R or ineligible non-GCB DLBCL who are 3L+ with histology based on criteria established by the World Health Organization (WHO).
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.
• 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.
• Participants with prior central nervous system (CNS) disease that have been effectively treated may be eligible.

Exclusion Criteria:

• Previously treated with a Bruton's tyrosine kinase (BTK) degrader.
• Known active CNS disease, or primary CNS lymphoma.
• Uncontrolled active systemic infection, or active cytomegalovirus infection, known history of human immunodeficiency virus (HIV), active hepatitis B or C 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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 60 month study duration.	Drug: ABBV-101; Oral:Tablet
Experimental: Dose Expansion ABBV-101 R/R Chronic Lymphocytic Lymphoma (CLL); Participants with R/R CLL will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 60 month study duration.	Drug: ABBV-101; Oral:Tablet
Experimental: 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 60 month study duration.	Drug: ABBV-101; Oral:Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Two Years
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

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
Number of Participants with Response of Partial Response (PR) or Better per Disease-Specific Criteria	Number of participants with response of PR or better per disease-specific criteria.	Up to Approximately Two Years
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

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): June 7, 2027
• Study Completion (Estimated): June 7, 2027

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): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

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); Relapsed/refractory (R/R) or ineligible Diffuse large b-cell lymphoma (DLBCL); Waldenström macroglobulinemia (WM); Transformed Indolent non-Hodgkin's lymphoma (INHL); ABBV-101
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• 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