ABBV-383 for Multiple Myeloma

(CERVINO Trial)

Recruiting at 147 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Proteasome inhibitors, Immunomodulatory imides

Must not be taking: BCMA-targeted therapy

Disqualifiers: Neurologic, Psychiatric, Cardiovascular, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3.5 years

380 Participants Needed

Trial Summary

What is the purpose of this trial?

Multiple myeloma (MM) is a cancer of the blood's plasma cells. The cancer is typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can cause bone pain, fractures, infections, weaker bones, and kidney failure. Treatments are available, but MM can come back (relapsed) or may not get better (refractory) with treatment. This is a study to determine change in disease symptoms of etentamig compared to standard available therapies in adult participants with relapsed/refractory (R/R) MM. Etentamig is an investigational drug being developed for the treatment of R/R MM. This study is broken into 2 Arms; Arm A and Arm B. In Arm A, participants will receive etentamig as a monotherapy. In Arm B, participants will receive the standard available therapy (SAT) identified by the Investigator during screening, in accordance with the local (or applicable) approved label, package insert, summary of product characteristics, and/or the institutional guidelines, as applicable. Around 380 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 140 sites across the world. In Arm A participants will receive etentamig as an infusion into the vein in 28 day cycles, during the 3.5 year study duration. In Arm B, participants will receive the SAT identified by the Investigator during screening, in accordance with the local (or applicable) approved label, package insert, summary of product characteristics, and/or the institutional guidelines, as applicable, during the 3.5 year 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 a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. However, in Arm B, you will receive standard available therapy based on your previous treatment history, which might mean continuing some existing medications.

What data supports the effectiveness of the drug ABBV-383 for treating multiple myeloma?

Research shows that ABBV-383, a bispecific antibody targeting BCMA and CD3, has shown promising results in early human trials for patients with relapsed or hard-to-treat multiple myeloma. Similar treatments targeting BCMA have demonstrated the ability to effectively kill multiple myeloma cells and activate the immune system to fight the cancer. ^{1 2 3 4 5}

What safety data exists for ABBV-383 in humans?

In a phase I study, ABBV-383 was tested in patients with relapsed/refractory multiple myeloma and showed promising safety outcomes. Another study on a similar bispecific antibody, TNB-383B, indicated mild increases in cytokines (proteins involved in inflammation) but no significant safety concerns. ^{1 2 3 4 6}

What makes the drug ABBV-383 unique for treating multiple myeloma?

ABBV-383 is a novel treatment for multiple myeloma that works by engaging the body's own T-cells to target and kill cancer cells. It is a bispecific antibody, meaning it can bind to two different targets: the B-cell maturation antigen (BCMA) on myeloma cells and CD3 on T-cells, effectively redirecting the immune system to attack the cancer. ^{1 3 4 5 6}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults with multiple myeloma that has returned or hasn't improved after treatment. They must have had at least two prior therapies, including specific inhibitors and antibodies, but not BCMA-targeted therapy. Participants need to be physically able to perform daily activities with some limitations (ECOG <=2) and meet certain lab criteria.

Inclusion Criteria

I can do most of my daily activities on my own.

You have more than 200 milligrams of M-protein in your urine over a 24-hour period.

If you don't have a specific protein in your blood or urine, another type of protein in your blood needs to be above a certain level.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive etentamig or standard available therapy in 28-day cycles for up to 3.5 years

3.5 years

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• ABBV-383

Trial Overview The study compares ABBV-383 given intravenously in 28-day cycles against standard available therapies chosen by the investigator. It aims to see how well ABBV-383 works compared to these treatments over a period of 3.5 years in about 380 participants worldwide.

Participant Groups

Group I: Standard Available Therapy (SAT) Experimental Treatment 6 Interventions

Participants will receive SAT, in accordance with the local (or applicable) approved label, package insert, summary of product characteristics, and/or the institutional guidelines, as applicable. SAT choices are carfilzomib + dexamethasone (Kd), elotuzumab + pomalidomide + dexamethasone (EloPd), selinexor + bortezomib + dexamethasone (SVd).

Group II: Etentamig Experimental Treatment 1 Intervention

Participants will receive etentamig as a monotherapy.

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

Findings from Research

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]

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]

The bispecific antibody BiFab-BCMA effectively redirects T cells to attack multiple myeloma cells, showing up to 20 times greater potency than a similar antibody targeting CS1.

BiFab-BCMA not only activates T cells in laboratory settings but also leads to rapid tumor regression in animal models, suggesting it could be a promising alternative to existing CAR-T therapies for treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-B cell maturation antigen bispecific antibody for multiple myeloma. Ramadoss, NS., Schulman, AD., Choi, SH., et al.[2015]

The fully human bispecific antibody REGN5458, which targets B-cell maturation antigen (BCMA) and CD3, effectively induces T-cell killing of multiple myeloma cells and shows strong antitumor activity in mouse models, demonstrating its potential as a rapid therapeutic option.

In head-to-head comparisons, REGN5458 cleared tumors more quickly than anti-BCMA CAR T cells, suggesting that bispecific antibodies can engage existing T cells at the tumor site for immediate action, while CAR T cells require time to activate and expand before they can attack the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A BCMAxCD3 bispecific T cell-engaging antibody demonstrates robust antitumor efficacy similar to that of anti-BCMA CAR T cells. DiLillo, DJ., Olson, K., Mohrs, K., et al.[2021]

References

1. United States 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Bispecific antibodies and dual-targeting CAR-T cells for multiple myeloma: latest updates from the 2023 ASCO annual meeting. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Ex vivo efficacy of BCMA-bispecific antibody TNB-383B in relapsed/refractory multiple myeloma. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

An anti-B cell maturation antigen bispecific antibody for multiple myeloma. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

A BCMAxCD3 bispecific T cell-engaging antibody demonstrates robust antitumor efficacy similar to that of anti-BCMA CAR T cells. [2021]