ABBV-383 Combo for Multiple Myeloma

Recruiting at 79 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must be taking: Etentamig, Pomalidomide, Lenalidomide, Daratumumab

Disqualifiers: Nonsecretory MM, Plasma cell leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

320 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of a new drug, etentamig, for individuals with relapsed or hard-to-treat multiple myeloma, a blood cancer affecting plasma cells in the bone marrow. Participants will receive etentamig combined with other medications such as pomalidomide, lenalidomide, or daratumumab to evaluate the effectiveness of these combinations. The trial includes multiple treatment groups to determine the best dose of etentamig. This trial may suit those previously treated for multiple myeloma who need new options, especially if they haven't tried etentamig or similar drugs targeting BCMA (a protein on plasma cells). Participants must visit the study site regularly for check-ups and assessments. As a Phase 1 trial, this research focuses on understanding how etentamig works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves new drug combinations, it's best to discuss your current medications with the study doctors to ensure safety and compatibility.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ABBV-383, also known as etentamig, holds promise for treating relapsed or refractory multiple myeloma. An ongoing study is testing ABBV-383 with other drugs—pomalidomide, lenalidomide, and daratumumab—all combined with dexamethasone. These combinations are under study to evaluate their effectiveness and safety.

ABBV-383 targets a protein called BCMA on cancer cells, aiding the immune system in attacking these cells. Earlier studies found that ABBV-383 was generally well-tolerated by patients, with mostly mild or moderate side effects reported. Serious side effects were less common.

Pomalidomide, lenalidomide, and daratumumab are already used in other multiple myeloma treatments, and their safety profiles are well-known. Most patients tolerate them well, though some experience side effects like tiredness or low blood counts.

The current study is in an early phase, with researchers still determining the optimal dose of etentamig. While more data is needed, existing research suggests that the treatment combinations are generally safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they incorporate etentamig, which introduces a novel approach compared to existing therapies. Most standard treatments, like bortezomib and lenalidomide, target specific proteins in cancer cells to inhibit their growth. However, etentamig works differently by potentially engaging the immune system in a more targeted way to fight multiple myeloma cells. This innovative mechanism could offer a new avenue for treating relapsed or refractory multiple myeloma, possibly improving effectiveness for patients who haven't responded well to traditional therapies.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that etentamig (ABBV-383) could be a promising treatment for relapsed or refractory multiple myeloma (R/R MM). It targets a protein called BCMA on myeloma cells and another protein called CD3 on T-cells, helping T-cells attack the cancer cells. In this trial, participants will receive etentamig in combination with other drugs. Specifically, some participants will receive etentamig with pomalidomide and dexamethasone, others with lenalidomide and dexamethasone, and others with daratumumab and dexamethasone. Studies have found these combinations effective in treating this type of cancer, with patients in earlier studies experiencing a decrease in disease activity. In summary, etentamig shows promise as part of a combination therapy for people with hard-to-treat multiple myeloma. ^{6 7 8 9 10}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with relapsed/refractory multiple myeloma who've had previous treatments can join this trial. They must have a certain level of physical ability (ECOG <=2), measurable disease, and no prior BCMA-targeted therapy. Exclusions include recent major surgery, active infections or uncontrolled conditions like diabetes or hypertension, recent stem cell transplants, unresolved side effects from past cancer therapies, central nervous system involvement in MM, and certain other medical conditions.

Inclusion Criteria

My multiple myeloma has returned or didn't respond to treatment, as confirmed by tests.

I can take care of myself but might not be able to do heavy physical work.

You must have a specific amount of disease that can be measured as described in the study plan.

Exclusion Criteria

I have severe nerve pain or damage in my hands or feet.

My multiple myeloma has spread to my brain or spinal cord.

You have a current infection of hepatitis B, hepatitis C, or HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of etentamig to determine the best dose

28 days

Regular visits at an approved institution

Dose Expansion

Participants receive the confirmed dose of etentamig to further assess safety and efficacy

28-day cycles

Regular visits at an approved institution

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-383
• Daratumumab
• Dexamethasone
• Lenalidomide
• Nirogacestat
• Pomalidomide

Trial Overview The study is testing ABBV-383 combined with anti-cancer regimens (Pd/Rd/Dd/Niro) for safety and effect on disease activity in multiple myeloma patients. Participants are grouped to receive different combinations intravenously over 28-day cycles. The trial includes phases to find the best dose of ABBV-383 and confirm it through more participants at various global sites.

How Is the Trial Designed?

Group I: Part 2: Arm E (Etentamig with Pomalidomide and Dexamethasone) Experimental Treatment 3 Interventions

Participants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone, after 1-3 prior lines of therapy.

Group II: Part 1: Arm C (Etentamig with Daratumumab and Dexamethasone) Experimental Treatment 3 Interventions

Participants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Daratumumab and Dexamethasone.

Group III: Part 1: Arm B (Etentamig with Lenalidomide and Dexamethasone) Experimental Treatment 3 Interventions

Participants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Lenalidomide and Dexamethasone.

Group IV: Part 1: Arm A (Etentamig with Pomalidomide and Dexamethasone) Experimental Treatment 3 Interventions

Participants with relapsed or refractory (R/R) multiple myeloma (MM) who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

TeneoOne Inc.

Lead Sponsor

Trials

5

Recruited

860+

Published Research Related to This Trial

TNB-383B effectively induces the killing of plasma cells in bone marrow from patients with relapsed multiple myeloma, showing dose-dependent lysis starting at very low doses (0.001 μg).

The treatment leads to significant degranulation of cytotoxic T lymphocytes (CTLs) and modulates cytokine responses, with notable increases in IL-2/TNFα and IP10, indicating a robust immune response without significant T cell expansion or severe cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo efficacy of BCMA-bispecific antibody TNB-383B in relapsed/refractory multiple myeloma. Foureau, DM., Bhutani, M., Robinson, M., et al.[2023]

The study developed several bispecific BCMA-CD3 antibodies that effectively target and kill multiple myeloma cells, demonstrating specific binding and cytotoxic activity in vitro with a strong affinity in the nanomolar range.

In vivo testing in a mouse model showed that these BCMA bispecific antibodies had high efficacy against multiple myeloma, supporting their potential for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth. Wu, L., Huang, Y., Sienkiewicz, J., et al.[2022]

A 76-year-old female patient with relapsed/refractory multiple myeloma achieved stringent complete remission after receiving a multi-agent salvage therapy called Pom-PAD-Dara, which includes pomalidomide, bortezomib, doxorubicin, dexamethasone, and the CD38 antibody daratumumab, after previously failing treatment with pomalidomide and another CD38 antibody.

The patient has maintained progression-free survival for over 12 months, highlighting the potential effectiveness of retreating with CD38 antibodies in patients who have developed resistance to prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma. Steinhardt, MJ., Zhou, X., Krummenast, F., et al.[2021]

The antibody-drug conjugate MEDI2228 enhances the effectiveness of immunotherapies for multiple myeloma by activating key signaling pathways that increase CD38 expression and improve immune response, even in drug-resistant cancer cells.

In combination with the CD38 monoclonal antibody daratumumab, MEDI2228 significantly boosts NK cell-mediated cytotoxicity against multiple myeloma cells, suggesting a promising strategy for improving treatment outcomes in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCMA-Specific ADC MEDI2228 and Daratumumab Induce Synergistic Myeloma Cytotoxicity via IFN-Driven Immune Responses and Enhanced CD38 Expression. Xing, L., Wang, S., Liu, J., et al.[2022]

Immunotherapies, particularly bispecific antibodies (BsAb) targeting BCMA, are showing promise as innovative treatments for multiple myeloma (MM) by effectively engaging the immune system to attack cancer cells.

BsAb can bind to both tumor cell antigens and T cell receptors, creating a stronger immune response, but there are concerns about potential mechanisms of resistance that may limit their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bispecific antibodies in multiple myeloma]. Escure, G., Manier, S.[2021]

BCMA-directed T-cell immunotherapies, like CAR T-cells and bispecific antibodies, have significantly improved survival rates in patients with triple-class refractory multiple myeloma, but many still experience disease progression, highlighting the need for new treatments.

Novel bispecific antibodies targeting alternative antigens, such as GPRC5D and FcRH5, show promise in heavily pretreated multiple myeloma patients, although they come with potential toxicities like cytokine-release syndrome and specific side effects like rash and nail disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA. van de Donk, NWCJ., O'Neill, C., de Ruijter, MEM., et al.[2023]

ABBV-383, a bispecific antibody targeting B-cell maturation antigen and CD3, showed a promising overall response rate (ORR) of 68% in patients with relapsed/refractory multiple myeloma (RRMM) at doses of 40 mg or higher, indicating its potential efficacy as a treatment option.

The treatment was generally well tolerated, with common side effects including neutropenia (37%) and cytokine release syndrome (57%), and no deaths were deemed related to the study drug, suggesting a favorable safety profile for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen × CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma. D'Souza, A., Shah, N., Rodriguez, C., et al.[2023]

Bispecific antibodies (BsAbs) and dual-targeted CAR T cells have shown promising results in treating relapsed/refractory multiple myeloma (RRMM) patients, particularly those who have not responded to at least three prior therapies.

Recent data from the 2023 ASCO annual meeting highlight that combinations targeting BCMA/CD3 and GPRC5D/CD3 lead to stronger and more durable responses in patients, indicating their potential effectiveness in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific antibodies and dual-targeting CAR-T cells for multiple myeloma: latest updates from the 2023 ASCO annual meeting. Hou, J., Li, Y., Lin, Q.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10657518/

Bispecific antibody treatment of multiple myeloma This article provides an overview of the latest advances in BsAbs immunotherapy for refractory and relapsed MM and highlights significant findings from the ...

2. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper205083.html

Paper: ABBV-383 Plus Daratumumab-Dexamethasone in ... ABBV-383 is a fully human bispecific antibody that targets B-cell maturation antigen (BCMA) and CD3 on the surface of multiple myeloma (MM) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06892522

NCT06892522 | A Study to Assess Change in Disease ... A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving Etentamig (ABBV-383) as an ...

4. multiplemyelomahub.com multiplemyelomahub.com/medical-information/etentamig-combined-with-daratumumabdexamethasone-for-rr-mm-results-from-the-phase-i-kilimanjaro-trial

Etentamig combined with daratumumab/dexamethasone ... Etentamig (ABBV-383) is a BCMA- and CD3-directed bispecific antibody with previously demonstrated efficacy in treating heavily pretreated ...

5. withpower.com withpower.com/trial/phase-1-neoplasms-plasma-cell-3-2022-083fb

ABBV-383 Combo for Multiple Myeloma This trial tests a new drug, ABBV-383, combined with other medications to treat adults with difficult-to-treat multiple myeloma. The study aims to find the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9175895/

Ex vivo efficacy of BCMA‐bispecific antibody TNB‐383B in ... TNB‐383B is a fully human BCMA‐targeting T‐cell engaging bispecific monoclonal antibody (T‐BsAb). We assessed ex vivo efficacy of this drug to mediate ...

7. myeloma.org myeloma.org/sparkcures/trial/2149

Etentamig (ABBV-383) Carfilzomib Carfilzomib is a kind of medication called a proteasome inhibitor that interferes with the growth and spread of cancer cells in the body.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05259839

NCT05259839 | A Study to Assess Adverse Events and ... The purpose of this study is to assess the safety and toxicity of etentamig (ABBV-383) when co-administered with pomalidomide-dexamethasone (Pd), lenalidomide- ...

9. news.abbvie.com news.abbvie.com/2024-06-05-AbbVie-Advances-Oncology-Pipeline-With-Start-of-Multiple-Myeloma-Phase-3-Clinical-Trial-for-Investigational-Asset-ABBV-383

AbbVie Advances Oncology Pipeline With Start of Multiple ... ABBV-383 is a B-cell maturation antigen (BCMA) bispecific antibody T-cell engager being evaluated in relapsed/refractory multiple myeloma ...

10. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.22.01504

A Phase I First-in-Human Study of ABBV-383, a B-Cell ... This trial describes outcomes with ABBV-383, an anti B-cell maturation antigen 3 CD3 bispecific monoclonal antibody in patients with relapsed/ ...