ABBV-383 for Amyloidosis

Recruiting at 20 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AbbVie

Must be taking: Proteasome inhibitors, Anti-CD38 antibodies

Disqualifiers: Multiple myeloma, Plasma cell leukemia, others

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

Compensation: Varies

Number of Visits: Unknown

76 Participants Needed

Trial Summary

Do I need to stop my current medications for the ABBV-383 trial?

The trial information does not specify if you need to stop taking 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 amyloidosis?

The drug ABBV-383 has shown promising results in a study for multiple myeloma, a type of blood cancer, by effectively targeting and killing cancer cells. This suggests potential effectiveness in treating amyloidosis, as both conditions involve abnormal protein accumulation. ^{1 2 3 4 5}

What safety data exists for ABBV-383 in humans?

In a phase I study of ABBV-383 for multiple myeloma, the most common side effect was cytokine release syndrome (a reaction that can cause fever and low blood pressure), which was manageable with medications like tocilizumab or steroids. Safety evaluations in animal studies suggested that the bispecific antibody format, like ABBV-383, might have a better safety profile compared to other treatment formats. ^{1 2 4 5 6}

How does the drug ABBV-383 differ from other treatments for amyloidosis?

ABBV-383 is a unique drug because it is a bispecific antibody that targets both BCMA (a protein found on certain cancer cells) and CD3 (a protein on T-cells), helping the immune system to directly attack and kill cancer cells. This mechanism is different from traditional treatments, as it actively engages the body's own T-cells to fight the disease. ^{1 2 4 5 7}

What is the purpose of this trial?

Immunoglobulin light chain (AL) amyloidosis is the most common form of systemic amyloidosis. AL amyloidosis has many root causes and is characterized by the overproduction of AL that are secreted by clonal bone marrow plasma cells. This is a study to determine adverse events and change in disease activity in adult participants with AL amyloidosis treated with ABBV-383. Etentamig (ABBV-383) is an investigational drug being developed for the treatment of AL amyloidosis. This study in broken into 2 parts (dose escalation and safety expansion) with 5 arms. During dose escalation (arms 1-3) participants will receive 1 of 3 doses of ABBV-383 to determine the part 2 doses. After completion of the dose escalation portion of the study, the safety expansion (part 2) portion of the study will begin. Two arms (arm 4-5) will begin and participants will receive 1 of 2 doses as determined during the dose escalation portion (part 1). Around 76 adult participants with relapsed/refractory AL amyloidosis will be enrolled at approximately 20 sites across the world. Participants will receive Etentamig (ABBV-383) as an infusion into the vein for up to approximately 2 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.

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults with AL amyloidosis, a condition where abnormal proteins build up in organs. Participants must have had prior treatments including proteasome inhibitors and anti-CD38 antibodies, be moderately healthy (ECOG <=2), and have measurable disease impact on at least one organ.

Inclusion Criteria

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

I have been treated with drugs targeting proteins and CD38 before.

I have been diagnosed with AL amyloidosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive one of three doses of ABBV-383 to determine the doses for the next phase

Up to 2 years

Regular visits at a hospital or clinic

Safety Expansion

Participants receive one of two doses determined during the dose escalation phase

Up to 2 years

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• ABBV-383

Trial Overview The study tests ABBV-383, an experimental drug for AL amyloidosis. It has two parts: first to find the right dose and second to assess safety at selected doses. Patients receive the drug through IV over approximately two years across various global sites.

Participant Groups

Group I: Safety Expansion: ABBV-383 (etentamig) Expansion B Experimental Treatment 1 Intervention

Participants will receive ABBV-383 (etentamig) expansion dose B during the approximately 2 year study duration.

Group II: Safety Expansion: ABBV-383 (etentamig) Expansion A Experimental Treatment 1 Intervention

Participants will receive ABBV-383 (etentamig) expansion dose A during the approximately 2 year study duration.

Group III: Dose Escalation: ABBV-383 (etentamig) Dose C Experimental Treatment 1 Intervention

Participants will receive ABBV-383 (etentamig) dose C during the approximately 2 year study duration.

Group IV: Dose Escalation: ABBV-383 (etentamig) Dose B Experimental Treatment 1 Intervention

Participants will receive ABBV-383 (etentamig) dose B during the approximately 2 year study duration.

Group V: Dose Escalation: ABBV-383 (etentamig) Dose A Experimental Treatment 1 Intervention

Participants will receive ABBV-383 (etentamig) dose A during the approximately 2 year 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

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]

In a phase 3 trial involving 260 newly diagnosed patients with AL amyloidosis, birtamimab did not show a significant improvement in overall survival or hospitalization rates compared to placebo, leading to the trial's early termination due to futility.

However, a post hoc analysis revealed that patients with Mayo stage IV AL amyloidosis treated with birtamimab had a significant survival advantage at 9 months, with 74% survival compared to 49% in the placebo group, suggesting potential efficacy in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Birtamimab plus standard of care in light-chain amyloidosis: the phase 3 randomized placebo-controlled VITAL trial. Gertz, MA., Cohen, AD., Comenzo, RL., et al.[2023]

BCMA-targeting bispecific antibodies, like teclistamab, show significant effectiveness in treating heavily pretreated multiple myeloma patients, utilizing mechanisms such as T-cell redirection to eliminate cancer cells.

Cytokine release syndrome is the most common side effect of these treatments, but it can be effectively managed with medications like tocilizumab or steroids, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell redirecting bispecific antibodies targeting BCMA for the treatment of multiple myeloma. Verkleij, CPM., Frerichs, KA., Broekmans, M., et al.[2020]

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 study compared the efficacy of a CD3 bispecific antibody and two types of antibody-drug conjugates (ADCs) targeting B-cell maturation antigen (BCMA) in treating myeloma, showing that both modalities effectively killed myeloma cells in vitro and in vivo.

The CD3 bispecific antibody demonstrated superior potency and consistency in killing primary patient cells compared to ADCs, leading to its advancement into phase I clinical trials due to its better efficacy and improved toxicity profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma. Panowski, SH., Kuo, TC., Zhang, Y., et al.[2020]

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

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

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

Birtamimab plus standard of care in light-chain amyloidosis: the phase 3 randomized placebo-controlled VITAL trial. [2023]

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

T-cell redirecting bispecific antibodies targeting BCMA for the treatment of multiple myeloma. [2020]

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

Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma. [2020]

7. 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]