ABBV-383 for Multiple Myeloma

Recruiting at 14 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

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 the safety and pharmacokinetics of ABBV-383 in adult participants with relapsed/refractory (R/R) MM. ABBV-383 is an investigational drug being developed for the treatment of R/R MM. This study is broken into 3 Arms: Arm A with 2 parts and Arm B as an expansion. Participants will receive ABBV-383 as a subcutaneous (SC) injection and intravenous (IV) infusion in Arm A and SC injections of ABBV-383 in Arm B. Around 55 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 25 sites across the world In Arm A participants will receive one of two doses of ABBV-383 as an SC injection and (IV) infusions, during the 151 week study duration. In Arm B, participants will receive the selected dose from Arm A as SC injections, during the 151 week 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. It's best to discuss this with the trial coordinators or your doctor.

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 cell signaling) associated with immune responses, suggesting a generally manageable safety profile. ^{2 3 4 5 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 2 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. 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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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

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

2. 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]

3. 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]

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

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]