Alnuctamab + Mezigdomide for Multiple Myeloma

Not currently recruiting at 27 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment combination for individuals with multiple myeloma, a type of blood cancer, who have not succeeded with previous treatments. The study aims to determine the optimal dose and schedule for alnuctamab (an experimental treatment) and mezigdomide (a cereblon modulator) to ensure safety and potential effectiveness. Participants must have a diagnosis of relapsed or refractory multiple myeloma and have undergone at least one prior treatment. This trial will help researchers understand how well these medicines might work together for those who have exhausted other options. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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.

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

Research shows that both alnuctamab and mezigdomide are under investigation for their safety in treating multiple myeloma. Previous studies tested mezigdomide, a drug that helps the immune system attack cancer cells, on patients with multiple myeloma. These studies found that patients could tolerate it, although some experienced side effects.

For alnuctamab, less safety information is available because research is still in the early stages. However, testing these treatments together in clinical trials suggests that researchers believe they could be safe for people with multiple myeloma. Since this trial is in an early phase, it mainly focuses on understanding how the treatments work together and finding the best dose. Safety remains a key focus of the study. If considering joining this trial, discussing these findings with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Alnuctamab and Mezigdomide because they offer a fresh approach to treating multiple myeloma. Unlike standard treatments like proteasome inhibitors and immunomodulatory drugs, Alnuctamab is designed to engage the immune system differently by targeting specific proteins on cancer cells, potentially enhancing the body’s natural ability to fight the cancer. Mezigdomide introduces a novel mechanism as a cereblon E3 ligase modulator, aiming to degrade proteins that help cancer cells survive. This combination could offer a more targeted and effective treatment option, providing hope for better outcomes in patients with multiple myeloma.

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

Research has shown that alnuctamab, one of the treatments in this trial, has strong effects against tumors in people with relapsed and hard-to-treat multiple myeloma. In one study, 77% of participants responded well to the treatment over time, with patients living an average of 10.1 months without disease progression.

Mezigdomide, another treatment option in this trial, is a new drug that targets a protein involved in cell growth. It has shown promising results when combined with dexamethasone, especially for patients whose multiple myeloma has returned after other treatments. This combination has been effective for patients who have undergone many previous treatments. The trial will explore whether alnuctamab and mezigdomide work better together than individually. ^{6 7 8 9 10}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2011/498889/Alnuctamab-ALNUC-BMS-986349-CC-93269-a-2-1-B-Cell

Alnuctamab (ALNUC; BMS-986349; CC-93269), a 2+1 B-Cell ... Secondary objectives included preliminary efficacy and pharmacokinetics. The data cutoff for the results included herein was Apr 3, 2023; ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10431068/

BMS-986349; CC-93269), A BCMA × CD3 T-CELL ... ALNUC, a 2 + 1 T-cell engager (TCE) with bivalent binding to BCMA, has demonstrated clinical activity in pts with RRMM in an open-label phase 1 study.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06232707

NCT06232707 | A Study to Evaluate Efficacy and Safety of ... The purpose of this study is to evaluate the efficacy and safety of alnuctamab compared to standard of care regimens in participants with relapsed or refractory ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123086147

Alnuctamab (ALNUC; BMS-986349; CC-93269), a 2+1 B- ... High antitumor activity was observed at target doses ≥ 30 mg and specifically at the 30-mg target dose. Enrollment in the phase 1 study is ongoing.

5. sparkcures.com sparkcures.com/treatment/311/alnuctamab

Alnuctamab Myeloma Trials Median time to response was 1.2 mo (range, 0.9–4.0) and 77% (30/39) of responses were ongoing at data cutoff. Among efficacy-evaluable pts, median PFS was 10.1 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10969776/

Mezigdomide—A Novel Cereblon E3 Ligase Modulator ... Preclinical studies of mezigdomide have demonstrated its anti-proliferative and apoptotic effects in MM, along with its immune-stimulatory effects and its ...

7. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)00238-6/abstract

Cereblon E3 Ligase Modulators Mezigdomide and ... A study to evaluate safety, drug levels and effectiveness of CC-92480 (BMS-986348) in combination with other treatments in participants with ...

8. tandfonline.com tandfonline.com/doi/full/10.1080/14728214.2025.2575570?src=

Mezigdomide for multiple myeloma: a focus on phase 2 ... Mezigdomide (CC-92480), a novel cereblon E3 ligase modulator, induces vulnerability of multiple myeloma cells to T-cell-mediated killing.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12399888/

The Role of CELMoD Agents in Multiple Myeloma - PMC Iberdomide (CC-220) and mezigdomide (CC-92480) are promising oral CELMoD™ agents currently being evaluated for the treatment of patients with ...

10. clin.larvol.com clin.larvol.com/trial-detail/NCT03374085

A Safety, PK and Efficacy Study of CC-92480 Monotherapy ... The median duration of response (DOR) in the overall population was 7.6 months (95% CI, 5.4-9.5), although these data were immature, and the median progression- ...