ABBV-383 Combo for Multiple Myeloma

Recruiting at66 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: TeneoOne Inc.

Must be taking: Etentamig, Pomalidomide, Lenalidomide, Daratumumab

Disqualifiers: Nonsecretory MM, Plasma cell leukemia, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, ABBV-383, combined with other medications to treat adults with difficult-to-treat multiple myeloma. The study aims to find the safest and most effective dose while monitoring side effects and disease response. Participants will receive ongoing medical check-ups and tests throughout the trial.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves new drug combinations, it's best to discuss your current medications with the study doctors to ensure safety and compatibility.

What data supports the effectiveness of the drug ABBV-383 Combo for Multiple Myeloma?

Research shows that ABBV-383, a type of bispecific antibody, has shown promising results in early studies for patients with multiple myeloma who have not responded to other treatments. Bispecific antibodies, which target specific proteins on cancer cells and T-cells, have been effective in improving survival rates in similar cases. ^{1 2 3 4 5}

Is ABBV-383 safe for humans?

In a phase I study, ABBV-383, a bispecific antibody for multiple myeloma, showed promising safety results, with ongoing evaluations to ensure its safety in humans. ^{1 2 3 6 7}

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

The ABBV-383 Combo drug is unique because it includes ABBV-383, a bispecific antibody that targets BCMA (a protein found on multiple myeloma cells) and CD3 (a protein on T-cells), helping the immune system directly attack cancer cells. This approach is novel compared to traditional treatments, as it engages the body's own immune cells to fight the cancer more effectively. ^{1 2 3 7 8}

Research Team

TeneoOne Inc

Principal Investigator

TeneoOne Inc.

Eligibility Criteria

Adults with relapsed/refractory multiple myeloma who've had previous treatments can join this trial. They must have a certain level of physical ability (ECOG <=2), measurable disease, and no prior BCMA-targeted therapy. Exclusions include recent major surgery, active infections or uncontrolled conditions like diabetes or hypertension, recent stem cell transplants, unresolved side effects from past cancer therapies, central nervous system involvement in MM, and certain other medical conditions.

Inclusion Criteria

My multiple myeloma has returned or didn't respond to treatment, as confirmed by tests.

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

You must have a specific amount of disease that can be measured as described in the study plan.

Exclusion Criteria

I have severe nerve pain or damage in my hands or feet.

My multiple myeloma has spread to my brain or spinal cord.

You have a current infection of hepatitis B, hepatitis C, or HIV.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of etentamig to determine the best dose

28 days

Regular visits at an approved institution

Dose Expansion

Participants receive the confirmed dose of etentamig to further assess safety and efficacy

28-day cycles

Regular visits at an approved institution

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 3 years

Treatment Details

Interventions

• ABBV-383 (Monoclonal Antibodies)
• Daratumumab (Monoclonal Antibodies)
• Dexamethasone (Other)
• Lenalidomide (Other)
• Nirogacestat (Other)
• Pomalidomide (Other)

Trial Overview The study is testing ABBV-383 combined with anti-cancer regimens (Pd/Rd/Dd/Niro) for safety and effect on disease activity in multiple myeloma patients. Participants are grouped to receive different combinations intravenously over 28-day cycles. The trial includes phases to find the best dose of ABBV-383 and confirm it through more participants at various global sites.

Participant Groups

Group I: Part 2: Arm E (Etentamig with Pomalidomide and Dexamethasone) Experimental Treatment 3 Interventions

Participants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone, after 1-3 prior lines of therapy.

Group II: Part 1: Arm C (Etentamig with Daratumumab and Dexamethasone) Experimental Treatment 3 Interventions

Participants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Daratumumab and Dexamethasone.

Group III: Part 1: Arm B (Etentamig with Lenalidomide and Dexamethasone) Experimental Treatment 3 Interventions

Participants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Lenalidomide and Dexamethasone.

Group IV: Part 1: Arm A (Etentamig with Pomalidomide and Dexamethasone) Experimental Treatment 3 Interventions

Participants with relapsed or refractory (R/R) multiple myeloma (MM) who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone.

Who Is Running the Clinical Trial?

TeneoOne Inc.

Lead Sponsor

Trials

5

Recruited

860+

Findings from Research

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 antibody-drug conjugate MEDI2228 enhances the effectiveness of immunotherapies for multiple myeloma by activating key signaling pathways that increase CD38 expression and improve immune response, even in drug-resistant cancer cells.

In combination with the CD38 monoclonal antibody daratumumab, MEDI2228 significantly boosts NK cell-mediated cytotoxicity against multiple myeloma cells, suggesting a promising strategy for improving treatment outcomes in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCMA-Specific ADC MEDI2228 and Daratumumab Induce Synergistic Myeloma Cytotoxicity via IFN-Driven Immune Responses and Enhanced CD38 Expression. Xing, L., Wang, S., Liu, 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]

Immunotherapies, particularly bispecific antibodies (BsAb) targeting BCMA, are showing promise as innovative treatments for multiple myeloma (MM) by effectively engaging the immune system to attack cancer cells.

BsAb can bind to both tumor cell antigens and T cell receptors, creating a stronger immune response, but there are concerns about potential mechanisms of resistance that may limit their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bispecific antibodies in multiple myeloma]. Escure, G., Manier, S.[2021]

BCMA-directed T-cell immunotherapies, like CAR T-cells and bispecific antibodies, have significantly improved survival rates in patients with triple-class refractory multiple myeloma, but many still experience disease progression, highlighting the need for new treatments.

Novel bispecific antibodies targeting alternative antigens, such as GPRC5D and FcRH5, show promise in heavily pretreated multiple myeloma patients, although they come with potential toxicities like cytokine-release syndrome and specific side effects like rash and nail disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA. van de Donk, NWCJ., O'Neill, C., de Ruijter, MEM., et al.[2023]

A 76-year-old female patient with relapsed/refractory multiple myeloma achieved stringent complete remission after receiving a multi-agent salvage therapy called Pom-PAD-Dara, which includes pomalidomide, bortezomib, doxorubicin, dexamethasone, and the CD38 antibody daratumumab, after previously failing treatment with pomalidomide and another CD38 antibody.

The patient has maintained progression-free survival for over 12 months, highlighting the potential effectiveness of retreating with CD38 antibodies in patients who have developed resistance to prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma. Steinhardt, MJ., Zhou, X., Krummenast, F., 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 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]

References

1. 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]

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

BCMA-Specific ADC MEDI2228 and Daratumumab Induce Synergistic Myeloma Cytotoxicity via IFN-Driven Immune Responses and Enhanced CD38 Expression. [2022]

3. 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]

4. France pubmed.ncbi.nlm.nih.gov

[Bispecific antibodies in multiple myeloma]. [2021]

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

T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma. [2021]

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

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

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