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

AbbVie

Status and phase: Terminated; Phase 1

Conditions: B-cell Lymphoma

Treatments: Drug: ABBV-623; Drug: ABBV-992

Study type: Interventional

Funder types: Industry

Identifiers

NCT04804254

2020-005196-12 (EudraCT Number)

M20-208

Details and patient eligibility

About

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.

Enrollment: 5 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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5 participants in 6 patient groups

Monotherapy in Dose Escalation: ABBV-623

Experimental group

Description:

Participants with Relapsed/Refractory (R/R) B-cell malignancies will receive escalating doses of ABBV-623.

Treatment:

Drug: ABBV-623

Monotherapy in Dose Escalation: ABBV-992

Experimental group

Description:

Participants with R/R B-cell malignancies will receive escalating doses of ABBV-992.

Treatment:

Drug: ABBV-992

Combination in Dose Escalation

Experimental group

Description:

Participants with R/R B-cell malignancies will receive escalating doses of ABBV-623 and ABBV-992.

Treatment:

Drug: ABBV-623

Drug: ABBV-992

Monotherapy in Dose Expansion: ABBV-623

Experimental group

Description:

Participants with R/R B-cell malignancies will receive ABBV-623 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.

Treatment:

Drug: ABBV-623

Monotherapy in Dose Expansion: ABBV-992

Experimental group

Description:

Participants with R/R B-cell malignancies will receive ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.

Treatment:

Drug: ABBV-992

Combination in Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: ABBV-623

Drug: ABBV-992