Alnuctamab + Mezigdomide for Multiple Myeloma

Recruiting at 26 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Celgene

Must not be taking: Alnuctamab, Mezigdomide

Disqualifiers: Others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 5 years

156 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the recommended dose and schedule, and evaluate the safety and preliminary efficacy of alnuctamab in combination with mezigdomide in participants with relapsed and/or refractory multiple myeloma.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 Alnuctamab + Mezigdomide for treating multiple myeloma?

Mezigdomide, part of the treatment, has shown strong anti-cancer activity in lab studies for multiple myeloma, even in cases where other drugs like lenalidomide and pomalidomide didn't work. Drugs similar to Mezigdomide, which target a protein called cereblon, have been key in improving outcomes for multiple myeloma patients. ^{1 2 3 4 5}

What makes the drug combination of Alnuctamab and Mezigdomide unique for treating multiple myeloma?

The combination of Alnuctamab and Mezigdomide is unique because Mezigdomide is a new type of drug that targets cereblon, a protein involved in cell growth, and has shown strong effects against multiple myeloma, even in cases where other similar drugs have failed. This makes it a promising option for patients with resistant forms of the disease. ^{1 2 3 5 6}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for people with multiple myeloma that has come back or didn't respond to treatment. They should have tried at least three other treatments before joining Part A, and one to three prior treatments for Parts B and C. Those who've already taken alnuctamab or mezigdomide can't participate.

Inclusion Criteria

I have relapsed or refractory multiple myeloma and have undergone 3 or more treatments for Part A, and 1 to 3 treatments for Parts B and C.

Exclusion Criteria

I have never been treated with alnuctamab or mezigdomide.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alnuctamab in combination with mezigdomide to determine the recommended dose and schedule, and evaluate safety and preliminary efficacy

Up to approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

Treatment Details

Interventions

• Alnuctamab
• Mezigdomide

Trial Overview The study is testing a combination of two drugs, Alnuctamab and Mezigdomide, along with Dexamethasone, in patients with relapsed/refractory multiple myeloma. It aims to find the best dose, schedule, safety profile, and early signs of effectiveness.

Participant Groups

Group I: Part A Experimental Treatment 3 Interventions

Group II: Arm C2 Experimental Treatment 1 Intervention

Group III: Arm C1 Experimental Treatment 3 Interventions

Group IV: Arm B2 Experimental Treatment 3 Interventions

Group V: Arm B1 Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Findings from Research

In a phase 1-2 study involving 178 patients with relapsed and refractory multiple myeloma, the combination of mezigdomide and dexamethasone demonstrated an overall response rate of 41%, indicating promising efficacy for this treatment in heavily pretreated patients.

The most common side effects were neutropenia and infections, which were mostly reversible, suggesting that while the treatment has myelotoxic effects, it does not present unexpected toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. Richardson, PG., Trudel, S., Popat, R., et al.[2023]

The study identified argonaute 2 (AGO2) as a key cereblon binding partner that is regulated by the immunomodulatory drug lenalidomide, which affects multiple myeloma (MM) cell survival.

Silencing AGO2 in MM cells led to significant cell death, suggesting that targeting AGO2 could be a promising strategy to overcome resistance to IMiDs like lenalidomide in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of the cereblon binding protein argonaute 2 plays an important role for multiple myeloma cell growth and survival. Xu, Q., Hou, YX., Langlais, P., et al.[2020]

Thalidomide and its derivatives, lenalidomide and pomalidomide, are FDA-approved immunomodulatory drugs that play a crucial role in treating multiple myeloma, confirmed by large phase 3 trials.

The review highlights the recently understood mechanism of action of these drugs, which involves binding to cereblon, and discusses potential resistance mechanisms that may limit their effectiveness in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cereblon binding molecules in multiple myeloma. Kortüm, KM., Zhu, YX., Shi, CX., et al.[2020]

Immunomodulatory drugs (IMiDs) have significantly improved the prognosis for multiple myeloma (MM) patients by targeting the cereblon (CRBN) protein, leading to the degradation of survival proteins in MM cells.

The review highlights the potential of next-generation CRBN E3 ligase modulators (CELMoDs) and proteolysis targeting chimeras (PROTACs) as innovative strategies for treating MM and other cancers by expanding the range of targetable proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CRL4CRBN E3 Ligase Complex as a Therapeutic Target in Multiple Myeloma. Barankiewicz, J., Salomon-Perzyński, A., Misiewicz-Krzemińska, I., et al.[2022]

Thalidomide and similar drugs are important treatments for multiple myeloma, as they target cereblon, a protein that plays a crucial role in protein degradation.

By binding to cereblon, these drugs change how the ubiquitin ligase complex works, leading to the destruction of Ikaros and Aiolos, which are key transcription factors needed for the growth of multiple myeloma cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From anecdote to targeted therapy: the curious case of thalidomide in multiple myeloma. Licht, JD., Shortt, J., Johnstone, R.[2021]

Iberdomide combined with dexamethasone demonstrated meaningful clinical activity in heavily pretreated patients with relapsed or refractory multiple myeloma, achieving an overall response rate of 32% in the dose-escalation cohort and 26% in the dose-expansion cohort, indicating its potential effectiveness even in difficult-to-treat cases.

The treatment was generally safe, with a recommended phase 2 dose established at 1.6 mg, although some patients experienced serious adverse events, including neutropenia and infections, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lonial, S., Popat, R., Hulin, C., et al.[2022]

References

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

Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Expression of the cereblon binding protein argonaute 2 plays an important role for multiple myeloma cell growth and survival. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Cereblon binding molecules in multiple myeloma. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

CRL4CRBN E3 Ligase Complex as a Therapeutic Target in Multiple Myeloma. [2022]

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

From anecdote to targeted therapy: the curious case of thalidomide in multiple myeloma. [2021]

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

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. [2022]