ABBV-383 for Multiple Myeloma

Recruiting at 16 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must not be taking: BCMAxCD3 bispecific

Disqualifiers: None

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

Compensation: Varies

Number of Visits: Unknown

Duration: 151 weeks

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ABBV-383, a bispecific antibody, for individuals with multiple myeloma—a type of blood cancer affecting plasma cells that can cause bone pain and kidney issues. The trial aims to assess the safety and efficacy of this treatment, particularly for those whose cancer has returned or not improved after previous treatments. Participants will receive the treatment through injections and infusions over approximately three years, with regular check-ups. Those who have undergone multiple treatments and have not yet tried ABBV-383 may be suitable candidates for this study. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects on people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that ABBV-383, a new treatment being tested for multiple myeloma, has shown promising results in early studies. This drug targets specific cells involved in the disease, helping the immune system fight the cancer more effectively.

In earlier studies with ABBV-383, most patients handled the treatment well, although some side effects were reported. The most common side effects included tiredness, nausea, and reactions at the injection site. These are similar to side effects seen with other treatments that work in the same way.

Since ABBV-383 is still in the early stages of testing, its full safety profile remains unknown. However, its testing in humans suggests that earlier lab and animal tests indicated reasonable safety. Every new treatment carries some risk, and participants in trials like this help researchers learn more about the safety and effectiveness of new drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ABBV-383 for multiple myeloma because it introduces a unique approach compared to existing treatments like proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Unlike these standard therapies, ABBV-383 is designed to be administered both as a subcutaneous injection and intravenous infusion, potentially offering flexibility and convenience in how patients receive treatment. Additionally, ABBV-383 targets specific pathways in multiple myeloma cells, which may enhance its effectiveness against the cancer. This innovative approach could mean improved outcomes and new hope for patients battling this challenging condition.

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

Research shows that ABBV-383, a new bispecific antibody, may help treat relapsed or refractory multiple myeloma (R/R MM). This drug targets a protein called BCMA on cancerous plasma cells and aids the immune system's T-cells in attacking these cancer cells. Early studies suggest that ABBV-383 can effectively help the body fight the cancer. In this trial, participants will receive different doses of ABBV-383. Initial trials showed positive responses, with cancer either reduced or halted in growth. These findings offer hope for those whose multiple myeloma hasn't responded to other treatments. ^{1 3 6 7 8}

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. Participants must have tried at least one prior therapy and be new to ABBV-383, with a decent ability to perform daily activities (ECOG <=2).

Inclusion Criteria

I have never been treated with ABBV-383.

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

I have multiple myeloma and have been treated with 3-5 different therapies including specific drug types.

Exclusion Criteria

I have received BCMAxCD3 bispecific antibody treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ABBV-383 as subcutaneous injections and intravenous infusions over a 151-week study duration

151 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-383

Trial Overview The study tests the safety and how the body processes ABBV-383, given as an injection under the skin (SC) or into a vein (IV). It's divided into three parts: two dosage levels in Arm A (both SC and IV), and selected dose from Arm A in Arm B.

How Is the Trial Designed?

Group I: ABBV-383 Expansion Experimental Treatment 1 Intervention

Participants will receive the selected dose from Arm A of ABBV-383 as SC injections, during the 151 week study duration.

Group II: ABBV-383 Dose B Experimental Treatment 2 Interventions

Participants will receive Dose B of ABBV-383 as an SC injection and IV infusions, during the 151 week study duration.

Group III: ABBV-383 Dose A Experimental Treatment 2 Interventions

Participants will receive Dose A of ABBV-383 as a subcutaneous (SC) injection and intravenous (IV) infusions, during the 151 week study duration.

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

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9622641/

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. nature.com nature.com/articles/s41408-024-01139-y

Bispecific antibodies in the treatment of multiple myeloma ABBV-383 (TNB-383B) is a next generation fully human BsAb targeting BCMA with low affinity binding to CD3 which at this time does not ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT228187

Pre-clinical development of TNB-383B, a fully human T-cell ... Pre-clinical development of TNB-383B, a fully human T-cell engaging bispecific antibody targeting BCMA for the treatment of multiple myeloma. download.

4. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=TNB383B.0001

A Study of TNB-383B in Participants With Relapsed or ... 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

5. researchgate.net researchgate.net/publication/346691339_Initial_Results_of_a_Phase_I_Study_of_TNB-383B_a_BCMA_x_CD3_Bispecific_T-Cell_Redirecting_Antibody_in_RelapsedRefractory_Multiple_Myeloma

Initial Results of a Phase I Study of TNB-383B, a BCMA x ... TNB-383B is a unique fully-human triple-chain BCMA × CD3 BsAb which is designed to have a unique αCD3 moiety that lyses target cells with ...

6. 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 ...

7. 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 ...

8. ash.confex.com ash.confex.com/ash/2023/webprogram/Paper182388.html

Updated Safety and Efficacy Results of Abbv-383, a BCMA ... ABBV-383 is an off-the-shelf, fully human B-cell maturation antigen (BMCA) X CD3 bispecific antibody with bivalent BCMA domain and low CD3 affinity.