ABBV-383 for Multiple Myeloma

(CERVINO Trial)

Recruiting at 212 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, etentamig (also known as ABBV-383), for individuals with multiple myeloma, a type of blood cancer that has returned after treatment or hasn't improved. The study compares etentamig to standard therapies to determine which is more effective at reducing symptoms. Participants will receive either etentamig alone or a standard therapy chosen by their doctor. Those who have undergone multiple myeloma treatments and whose disease has returned or not responded may be suitable for this trial. Participants must visit the hospital or clinic regularly for check-ups and tests. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that ABBV-383, also known as etentamig, has promising results. Early human studies tested etentamig for safety and its effects, suggesting it is generally well-tolerated. Although some participants experienced side effects, these were mostly manageable. These studies provided important information on the body's reaction to the treatment.

Being in a later phase of trials indicates that researchers have already collected extensive safety information. This stage of research usually focuses more on the drug's effectiveness, suggesting that early safety tests were successful.

For those considering joining a trial, it's important to know that while risks exist, researchers will closely monitor side effects and overall health throughout the study. This helps ensure participant safety as much as possible. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for multiple myeloma?

Researchers are excited about the treatments in this trial because they offer promising new ways to tackle multiple myeloma. Unlike the standard of care options like carfilzomib, elotuzumab, and selinexor combinations, ABBV-383 introduces a novel therapeutic approach. ABBV-383 is an innovative treatment that targets specific proteins on cancer cells, potentially leading to more effective and targeted attacks on the disease. Additionally, the trial includes etentamig, which is being tested as a monotherapy, offering a simplified treatment option that could reduce the complexity and side effects associated with combination therapies. These advancements might provide better outcomes and improved quality of life for patients battling this challenging condition.

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

Research has shown that ABBV-383, also known as etentamig, may help treat relapsed or refractory multiple myeloma. It targets a protein called BCMA on cancer cells and assists the body's T-cells (a type of immune cell) in attacking these cancer cells. Early studies have demonstrated that this method can reduce cancer in patients with multiple myeloma. Although more research is needed, the initial results are promising for those whose cancer hasn't improved with other treatments. In this trial, participants will receive either ABBV-383 or standard available therapy (SAT), which includes options like carfilzomib + dexamethasone, elotuzumab + pomalidomide + dexamethasone, or selinexor + bortezomib + dexamethasone. This experimental treatment aims to provide another option for patients facing this challenging condition. ^{1 2 3 4 5}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01504

A Phase I First-in-Human Study of ABBV-383, a B-Cell ... ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study.

2. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/etentamig

Definition of anti-BCMA/anti-CD3 T-cell engaging bispecific ... Upon administration, anti-BCMA/anti-CD3 T-cell engaging bispecific antibody ABBV-383 binds to both CD3 on cytotoxic T lymphocytes (CTLs) and BCMA found on BCMA- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03933735

NCT03933735 | A Study of TNB-383B in Participants With ... This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of TNB-383B, a BCMA x CD3 T-cell engaging bispecific ...

4. 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 killing ...

5. 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 ...