What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, particularly those involving combinations with dexamethasone, daratumumab, and lenalidomide, often result in a range of side effects. These can include hematologic toxicities such as neutropenia and thrombocytopenia, and nonhematologic toxicities like diarrhea, fatigue, upper respiratory tract infections, and muscle spasms. Specific regimens may also cause hyperglycemia, hypertension, and gastrointestinal issues like constipation and nausea. Additionally, treatments involving bortezomib and carfilzomib can lead to peripheral neuropathy, cardiac events, and renal failure. Monitoring and managing these side effects is crucial for patient safety and treatment efficacy.

What prior FDA approvals exist?

The FDA has approved several treatments for relapsed/refractory multiple myeloma that are similar to the regimens being studied with ABBV-453. These include combinations of dexamethasone with other agents such as bortezomib, lenalidomide, and daratumumab. Bortezomib, a proteasome inhibitor, was approved for use with dexamethasone after showing significant efficacy in clinical trials. Lenalidomide, an immunomodulatory drug, is often combined with dexamethasone and has shown improved outcomes in multiple myeloma patients. Daratumumab, an anti-CD38 monoclonal antibody, has been approved in combination with both lenalidomide and dexamethasone, as well as with bortezomib and dexamethasone, demonstrating high response rates and manageable toxicity profiles.

What other types of research exist?

Promising novel alternatives to ABBV-453 for treating relapsed/refractory multiple myeloma include CB-5083, a p97 inhibitor that disrupts protein homeostasis and has shown efficacy in preclinical models. Additionally, other investigational drugs such as venetoclax (a BCL2 inhibitor) and various Bruton tyrosine kinase (BTK) inhibitors like ibrutinib, acalabrutinib, and zanubrutinib are being explored for their potential in multiple myeloma treatment.

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Monoclonal Antibodies

ABBV-453 for Multiple Myeloma

Q: What is the mechanism of action of this treatment?

Common treatments for Multiple Myeloma (MM) include dexamethasone, daratumumab, and lenalidomide, often used in combination. Dexamethasone reduces inflammation and suppresses immune responses, helping control MM cell growth. Daratumumab targets CD38 on MM cells, leading to their destruction. Lenalidomide enhances the immune system's ability to attack MM cells and inhibits their growth. These mechanisms are crucial for selecting effective treatment combinations and managing side effects, ultimately improving patient outcomes.

Phase 1

Waitlist Available

Research Sponsored by AbbVie

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Documented diagnosis of multiple myeloma (MM) based on standard International Myeloma Working Group (IMWG) criteria

Eastern Cooperative Oncology Group (ECOG) performance status <= 1

Must not have

Part 2 only: Previous treatment with venetoclax or BCL-2 inhibitor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 36 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests ABBV-453, a new drug for adults with multiple myeloma that has come back or didn't respond to other treatments. The drug aims to stop cancer cell growth and is tested alone or with other medications to find the best treatment combination.

Who is the study for?

Adults with relapsed or refractory Multiple Myeloma who have measurable disease, meet specific lab criteria, and are in good enough health to participate. Those in earlier parts of the trial must have tried all other beneficial treatments without success. Later parts require having had 1-3 prior therapies but no previous treatment with certain inhibitors.

What is being tested?

The safety and effectiveness of ABBV-453 tablets for Multiple Myeloma are being tested. Participants will receive different combinations of ABBV-453 with dexamethasone, daratumumab, and lenalidomide across various groups to find the best dose and assess changes in their condition.

What are the potential side effects?

Potential side effects include those common to cancer medications such as fatigue, nausea, blood count changes, potential heart issues (due to ECG exclusions), and possibly unique effects from ABBV-453 which are being studied.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with multiple myeloma according to IMWG standards.

Select...

I am fully active and can carry on all pre-disease activities without restriction.

Select...

My multiple myeloma has not responded to or I cannot tolerate standard treatments including PIs, IMIDs, and anti-CD38.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been treated with venetoclax or a BCL-2 inhibitor before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 36 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 36 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 36 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Response Rate (ORR) per International Myeloma Working Group (IMWG) Criteria

Secondary study objectives

Neoplasm, Residual

Duration of Response (DOR)

Overall Survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Part 2: Arm 3Experimental Treatment4 Interventions

Participants will receive continuous doses of ABBV-453 in combination with daratumumab, lenalidomide, and dexamethasone in 28-day cycles.

Group II: Part 2: Arm 2Experimental Treatment3 Interventions

Participants will receive continuous doses of ABBV-453 in combination with daratumumab and dexamethasone in 28-day cycles.

Group III: Part 2: Arm 1Experimental Treatment2 Interventions

Participants will receive continuous doses of ABBV-453 in combination with dexamethasone in 28-day cycles.

Group IV: Part 1: Monotherapy Dose EscalationExperimental Treatment1 Intervention

Participants with relapsed or refractory (R/R) multiple myeloma (MM) will receive escalating doses of ABBV-453, until the maximum tolerated dose (MTD) is determined.

Group V: Japan CohortExperimental Treatment1 Intervention

Participants with R/R MM will receive escalating doses of ABBV-453, until the MTD is determined.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lenalidomide

2005

Completed Phase 3

~2240

Daratumumab

2014

Completed Phase 3

~2380

Dexamethasone

2007

Completed Phase 4

~2650

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Multiple Myeloma (MM) include dexamethasone, daratumumab, and lenalidomide, often used in combination. Dexamethasone reduces inflammation and suppresses immune responses, helping control MM cell growth. Daratumumab targets CD38 on MM cells, leading to their destruction. Lenalidomide enhances the immune system's ability to attack MM cells and inhibits their growth. These mechanisms are crucial for selecting effective treatment combinations and managing side effects, ultimately improving patient outcomes.

How best to use new therapies in multiple myeloma.The role of thalidomide in multiple myeloma.