Study to Evaluate Adverse Events, Change in Disease Activity, Movement of Oral ABBV-623 and ABBV-992 Tablets in the Body of Adult Participants With B-cell Cancers

A Phase 1 First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of ABBV-623 and ABBV-992 in Subjects With B-cell Malignancies

B-cell cancer is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). The main objective of this study is to evaluate the safety and efficacy of ABBV-623 and ABBV-992 given alone and in combination in treating B-cell cancers. Adverse events, change in disease activity and how the drug moves through the body of adult participants with B-cell cancers will be evaluated.

ABBV-623 and ABBV-992 are investigational drugs being developed for the treatment of B-cell cancer. Study doctors assign participants to one of six groups, called treatment arms. Approximately 105 adult participants with a diagnosis of B-cell cancer will be enrolled in the study at approximately 50 sites worldwide.

Participants in the combination expansion treatment arms will receive oral tablets of ABBV-623 and/or ABBV-992 once daily for 24 months. All other arms are treated until progression.

Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be evaluated by medical assessments and blood tests. Adverse events will be collected and assessed throughout the clinical trial.

Study Overview

• Status: Active, not recruiting
• Conditions: B-cell Lymphoma
• Intervention / Treatment: Drug: ABBV-623; Drug: ABBV-992

• Study Type: Interventional
• Enrollment (Anticipated): 105
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 226754
    • Tel Aviv-Yafo, Tel-Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 226755
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Hospital del Centro Comprensivo de Cancer de la UPR /ID# 225646
• Turkey
  • Ankara, Turkey, 06200
    • Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 226087
  • Izmir, Turkey, 35340
    • Dokuz Eylul University Medical Faculty /ID# 226085

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants must have documented diagnosis for one of the following B-cell malignancies: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Waldenström's macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), with measurable disease requiring treatment.
• Participants have relapsed or refractory to at least 2 prior systemic therapies.
• Combination Dose Expansion Only: Participants with documented diagnosis of CLL/SLL with measurable disease requiring treatment per by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• CLL/SLL, MCL, WM, MZL only: Prior Bruton's tyrosine kinase inhibitor (BTKi) exposure will be allowed if participant did not progress on active treatment and there is no evidence of resistance mutations.
• Renal, liver and hematological function lab values as determined in the protocol.
• For participants with prior BTK inhibitor exposure, no evidence of mutations which confer resistance to covalent BTK inhibitors.

Exclusion Criteria:

• Participants with indolent forms of non-Hodgkin lymphoma (NHL) that require immediate cytoreduction.
• Participants with prior B-cell lymphoma 2 (BCL2) inhibitor (BCL2i) exposure (except for participants in the ABBV-992 monotherapy cohort).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy in Dose Escalation: ABBV-623; Participants with Relapsed/Refractory (R/R) B-cell malignancies will receive escalating doses of ABBV-623.	Drug: ABBV-623; Oral Tablets
Experimental: Monotherapy in Dose Escalation: ABBV-992; Participants with R/R B-cell malignancies will receive escalating doses of ABBV-992.	Drug: ABBV-992; Oral Tablets
Experimental: Combination in Dose Escalation; Participants with R/R B-cell malignancies will receive escalating doses of ABBV-623 and ABBV-992.	Drug: ABBV-623; Oral Tablets; Drug: ABBV-992; Oral Tablets
Experimental: Monotherapy in Dose Expansion: ABBV-623; Participants with R/R B-cell malignancies will receive ABBV-623 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.	Drug: ABBV-623; Oral Tablets
Experimental: Monotherapy in Dose Expansion: ABBV-992; Participants with R/R B-cell malignancies will receive ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.	Drug: ABBV-992; Oral Tablets
Experimental: Combination in Dose Expansion; Participants with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) will receive ABBV-623 and ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.	Drug: ABBV-623; Oral Tablets; Drug: ABBV-992; Oral Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.	Up to approximately 25 months.
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-623	The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that ABBV-623 achieves in the blood after administration in a dosing interval.	Up to approximately 96 weeks
Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-623	The area under the plasma concentration-time curve (AUC; measured in h*ng/mL/mg) is a method of measurement of the total exposure of ABBV-623 in blood plasma.	Up to approximately 96 weeks
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-992	The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that ABBV-992 achieves in the blood after administration in a dosing interval.	Up to approximately 96 weeks.
Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-992	The area under the plasma concentration-time curve (AUC; measured in h*ng/mL/mg) is a method of measurement of the total exposure of ABBV-992 in blood plasma.	Up to approximately 96 weeks
Combination Dose Expansion: Overall Response Rate (ORR) (PR or Better by IWCLL Criteria) in Participants With R/R CLL/SLL	ORR is the proportion of R/R CLL/SLL participants achieving a response of PR or better per IWCLL without the use of new anti-cancer therapy.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation in Participants With R/R B-cell Malignancies: Percentage of Participants Achieving a Response of Partial Response (PR) or Better per Disease-Specific Response Criteria (e.g., IWCLL, Lugano, IWWM)	Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol.	Up to approximately 2 years
Dose Escalation in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better	Duration of Response (DOR) is defined as the time from the date of the participant's documented first response of PR or better to the date of documented disease progression or death due to the disease, whichever occurs first.	Up to approximately 2 years
Dose Escalation in Participants With R/R B-cell Malignancies: Time to Response (TTR)	Time to response, defined as the length of time from the date of first dose of study drug to the date of first response of PR or better per disease-specific response criteria.	Up to approximately 2 years
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Achievement of a Response of PR or Better	Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol.	Up to approximately 2 years
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better	Duration of Response (DOR) is defined as the time from the date of the participant's documented first response of PR or better to the date of documented disease progression or death due to the disease, whichever occurs first.	Up to approximately 2 years
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Time to Response (TTR)	Time to response, defined as the length of time from the date of first dose of study drug to the date of first response of PR or better per disease-specific response criteria.	Up to approximately 2 years
Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)	Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells.	Up to approximately 6 months
Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)	Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells.	Up to approximately 1 Year
Combination Dose Expansion in Participants With CLL/SLL: Percentage of Participants With Achievement of Peripheral Blood uMRD	Peripheral blood Undetectable minimal residual disease (uMRD) is described as less than one CLL cell per 10,000 leukocytes (or below 10^-4) or as specified in the protocol.	Up to approximately 96 weeks
Combination Dose Expansion in Participants With CLL/SLL: Duration of Response for Participants With a Response of PR or Better	Duration of response is defined as the time from the initial objective response to disease progression or death, whichever occurs first.	Up to approximately 2 years
Combination Dose Expansion in Participants With CLL/SLL: Time to Response	Time to response is defined by the time between the date of the first drug intake and the date of the first assessment having documented the response.	Up to approximately 2 years
Combination Dose Expansion in Participants with CLL/SLL: Progression Free Survival	Progression free survival (PFS) is defined as the duration from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first.	Approximately 2 years after study drug discontinuation
Combination Dose Expansion in Participants With CLL/SLL: Overall Survival	Overall Survival is defined as the number of days from the date the participant was randomized to the date of death.	Approximately 2 years after study drug discontinuation

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2021
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 16, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Estimate): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Cancer; Follicular Lymphoma; B-cell lymphoma; Diffuse Large B-cell Lymphoma; ABBV-623; ABBV-992; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL); Mantle Cell Lymphoma (MCL); Marginal Zone Lymphoma (MZL); Waldenström's Macroglobulinemia (WM)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: M20-208; 2020-005196-12 (EudraCT Number)

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.: Yes