Clinical trial NCT05753501: 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
Official title: First-in-Human Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of the BTK Degrader, ABBV-101, in Participants With B-cell Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hematologic Cancer
Keywords: 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)
Mantle cell lymphoma (MCL)
Follicular lymphoma (FL)
Marginal zone lymphoma (MZL)
Waldenström macroglobulinemia (WM)
Transformed Indolent non-Hodgkin's lymphoma (INHL)
Hematologic Cancer
ABBV-101
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2023-03-03
Enrollment: 244
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, 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 244 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 88 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101, as part of the approximately 88 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 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. 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.
* 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 or less than 12 weeks since achieving undetectable viral load in cases of prior active hepatitis C.

Primary outcomes:
measure: Number of Participants with Adverse Events (AE)
timeFrame: Up to Approximately 88 Months
measure: Change in Laboratory Parameters
timeFrame: Up to Approximately Two Years
measure: Change in Vital Signs
timeFrame: Up to Approximately Two Years
measure: Change in Electrocardiogram (ECG)
timeFrame: Up to Approximately Two Years
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of ABBV-101
timeFrame: Up to Approximately One Year
measure: Time to Cmax (Tmax) of ABBV-101
timeFrame: Up to Approximately One Year
measure: Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-101
timeFrame: Up to Approximately One Year
measure: Number of Participants with Response of Partial Response (PR) or Better Response (Overall Response) per Disease-Specific Criteria
timeFrame: Up to Approximately Two Years
measure: Duration of Response (DOR)
timeFrame: Up to Approximately Two Years
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Arizona Oncology Associates, PC-HOPE /ID# 252351
state: Arizona
city: Orange
country: United States
facility: UC Irvine Medical Center /ID# 263020
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center - Palo Alto /ID# 249683
state: California
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers - Lone Tree /ID# 252237
state: Colorado
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 249347
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center /ID# 249302
state: Massachusetts
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey /ID# 249323
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology - Albany Cancer Center /ID# 252240
state: New York
city: Lake Success
country: United States
facility: Northwell Health - Monter Cancer Center /ID# 250422
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center /ID# 249324
state: New York
city: Cincinnati
country: United States
facility: UC Health - Cincinnati /ID# 249299
state: Ohio
city: Eugene
country: United States
facility: Oncology Assoc. of Oregon PC - WVCI and Research Ctr - Springfield /ID# 249309
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 250341
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center /ID# 249293
state: Texas
city: Montreal
country: Canada
facility: CHUM Notre-Dame Hospital /ID# 253428
state: Quebec
city: Bordeaux
country: France
facility: Institut Bergonie /ID# 253664
state: Gironde
city: Montpellier Cedex 5
country: France
facility: CHU Montpellier - Hopital Saint Eloi /ID# 253666
state: Herault
city: Lille
country: France
facility: CHRU Lille - Hopital Claude Huriez /ID# 253665
state: Nord
city: Nantes
country: France
facility: CHU de Nantes, Hotel Dieu -HME /ID# 256248
state: Pays-de-la-Loire
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy /ID# 253662
state: Val-de-Marne
city: Paris
country: France
facility: Hôpital Saint-Louis /ID# 253663
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm /ID# 253742
state: Baden-Wuerttemberg
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg /ID# 254636
state: Bayern
city: Rostock
country: Germany
facility: Universitaetsmedizin Rostock /ID# 259657
state: Mecklenburg-Vorpommern
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes /ID# 257435
state: Saarland
city: Berlin
country: Germany
facility: Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 257431
city: Zerifin
country: Israel
facility: Yitzhak Shamir Medical Center /ID# 254566
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 251122
state: Tel-Aviv
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 259608
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 251123
state: Yerushalayim
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele /ID# 253531
state: Milano
city: Torino
country: Italy
facility: A.O.U. CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO - Ospedale Molinette /ID# 253530
state: Piemonte
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 250684
state: Chiba
city: Kyoto-shi
country: Japan
facility: Kyoto University Hospital /ID# 261837
state: Kyoto
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 250680
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital Of JFCR /ID# 260375
state: Tokyo
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda /ID# 260196
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 260447
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal /ID# 260450
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro /ID# 253655
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca /ID# 253656
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital /ID# 256242
state: Cambridgeshire
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary /ID# 255171
state: England
city: London
country: United Kingdom
facility: University College London Hospital /ID# 260202
state: Greater London
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust /ID# 253670
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: