TNB-383B for Multiple Myeloma

Not currently recruiting at 35 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Teneobio, Inc.

Must be taking: Proteasome inhibitors, Immunomodulatory imides, Anti-CD38 antibodies

Must not be taking: BCMA-targeted therapy

Disqualifiers: Other malignancy, CNS involvement, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a new treatment called TNB-383B for people with multiple myeloma, a type of blood cancer. Participants can try this treatment if their myeloma has returned or hasn't responded to at least three previous treatments. The trial will test different doses to determine the best one and assess its effects on the body. It suits those who have already undergone certain treatments and seek new options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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, you cannot have received any cancer treatment or major surgery within 21 days before starting the trial.

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

Research has shown that TNB-383B, a new treatment for multiple myeloma, has promising safety results from earlier studies. Patients generally tolerated TNB-383B well. In these studies, many patients responded positively, especially at higher doses, with 79% showing improvement at doses of 40 mg or more. This suggests the treatment can be effective while keeping side effects manageable.

In summary, earlier research indicates that TNB-383B is well-tolerated, with few severe side effects reported. However, as with any new treatment, individual experiences may vary, and ongoing trials will continue to collect more safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for multiple myeloma involve chemotherapy, targeted therapy, and immunotherapy. However, TNB-383B is unique because it works as a bispecific antibody, targeting both BCMA on myeloma cells and CD3 on T-cells, effectively bringing these immune cells directly to the cancer cells to destroy them. This dual-targeting approach could enhance the immune response against myeloma cells more effectively than current treatments. Researchers are excited about TNB-383B because it offers a more direct and potentially more powerful way to engage the body’s own immune system in fighting the disease. Additionally, the potential for different dosing strategies, as explored in the trial, might offer more flexibility and effectiveness in treatment.

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

Research has shown that TNB-383B could effectively treat relapsed or hard-to-treat multiple myeloma, a type of blood cancer. In studies, patients generally tolerated TNB-383B well, with 79% experiencing an improvement in their cancer symptoms at doses of 40 mg or more. This indicates that most participants saw a reduction in their cancer symptoms. TNB-383B aids the immune system in specifically targeting and destroying cancer cells. Early results suggest that TNB-383B might be a promising option for those who have already tried several other treatments. This trial will explore various dosing strategies, including dose escalation and expansion cohorts, to determine the most effective and tolerable dose for participants. ^{1 2 5 6 7}

Who Is on the Research Team?

TeneoOne Inc

Principal Investigator

TeneoOne Inc.

Are You a Good Fit for This Trial?

This trial is for people with Multiple Myeloma who've tried at least three previous treatments, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. They need to have certain levels of M-protein or free light chains in their blood and good kidney function. People can't join if they've had other cancers (with some exceptions), major heart issues, severe nerve damage, recent cancer treatment or surgery, or active infections.

Inclusion Criteria

You have a high level of M-protein in your blood.

Your blood test shows high levels of a specific protein called free light chain and an abnormal ratio of this protein in your blood.

Consents to a fresh pretreatment bone marrow tumor biopsy or has adequate archival bone marrow tumor tissue that was collected within 6 months prior to screening and without intervening treatment.

Exclusion Criteria

Has any medical or psychiatric condition which in the opinion of the investigator or study Medical Monitor places the participant at an unacceptably high risk for toxicities, could interfere with successful or safe delivery of therapy, or could interfere with evaluation of the investigational product or interpretation of participant safety or study results.

I have a history of specific blood, nerve, organ, hormone, protein, or skin conditions.

I have severe nerve damage in my hands or feet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of TNB-383B to determine the maximum tolerated dose or recommended phase 2 dose

Up to 21 days per cohort

Multiple visits (in-person) for dose administration and monitoring

Dose Expansion

Participants receive the recommended phase 2 dose to further evaluate safety and pharmacokinetics

Up to 48 months

Regular visits (in-person) every 3-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 48 months

What Are the Treatments Tested in This Trial?

Interventions

• TNB-383B

Trial Overview TNB-383B is being tested on patients with relapsed/refractory Multiple Myeloma. The study has four parts: testing different doses every three weeks (Arm A), expanding the dose group once the best dose is found (Arm B), and then further testing this dose every four weeks (Arm E) and every three weeks (Arm F).

How Is the Trial Designed?

Group I: Arm F: Monotherapy Dose C Experimental Treatment 1 Intervention

An expansion cohort will be enrolled at the recommended phase 2 Dose C.

Group II: Arm E: Monotherapy Once Every 4 Weeks (Q4W) Experimental Treatment 1 Intervention

An expansion cohort will be enrolled at the recommended phase 2 Dose A.

Group III: Arm B: Dose Expansion Dose B Experimental Treatment 1 Intervention

An expansion cohort will be enrolled at the recommended phase 2 Dose B.

Group IV: Arm B: Dose Expansion Dose A Experimental Treatment 1 Intervention

An expansion cohort will be enrolled at the recommended phase 2 Dose A.

Group V: Arm A: Dose Escalation Experimental Treatment 1 Intervention

Up to 15 cohorts of participants receiving sequentially ascending doses of TNB-383B are planned until maximum tolerated dose is reached or recommended phase 2 dose is identified.

Who Is Running the Clinical Trial?

Teneobio, Inc.

Lead Sponsor

Trials

4

Recruited

490+

TeneoOne Inc.

Lead Sponsor

Trials

5

Recruited

860+

AbbVie

Industry 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 treatment landscape for multiple myeloma (MM) has significantly improved, with four new drugs approved in 2015 alone, leading to better patient outcomes than seen in any other cancer over the past decade.

Several new investigational agents, such as Isatuximab and marizomib, show promising efficacy in clinical trials, indicating a strong potential for future regulatory approval and further advancements in MM treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New investigational drugs with single-agent activity in multiple myeloma. Rajan, AM., Kumar, S.[2022]

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]

DETT effectively inhibits the NFκB signaling pathway by downregulating key proteins and promoting apoptosis in multiple myeloma cells, as demonstrated through various assays and immunoblotting techniques.

In animal studies, DETT showed the ability to delay tumor growth in multiple myeloma without causing significant toxicity, highlighting its potential as a safe therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-leishmanial thiadiazine agent induces multiple myeloma cell apoptosis by suppressing the nuclear factor kappaB signalling pathway. Chen, G., Han, K., Xu, X., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9175895/

Ex vivo efficacy of BCMA‐bispecific antibody TNB‐383B in ... We assessed ex vivo efficacy of this drug to mediate killing of bone marrow mononuclear cells (BMMCs) freshly isolated from 10 patients with relapsed multiple ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121028871

A Phase 1 First-in-Human Study of Tnb-383B, a BCMA x ... TNB-383B in pts with RRMM is well tolerated with an ORR of 79% observed at doses ≥40 mg in the dose-escalation cohorts. Despite having a shorter ...

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. myeloma.org myeloma.org/videos/phase-1-first-human-study-tnb-383b-bcma-x-cd3-bispecific-t-cell-redirecting-antibody

A Phase 1 First-in-Human Study of TNB-383B, a BCMA x ... TNB-383B in pts with RRMM is well tolerated with an ORR of 79% observed at doses greater than or equal to 40 mg in the dose-escalation cohorts.

5. 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.

6. cancernetwork.com cancernetwork.com/view/strong-early-safety-efficacy-data-for-novel-bcma-targeted-therapy-tnb-383b-to-treat-relapsed-refractory-myeloma

Strong Early Safety, Efficacy Data for Novel BCMA ... TNB-383B was well tolerated and researchers saw significant responses when it was administered at a higher dose level for heavily pretreated ...

7. 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 ...