Novel Drug Combinations for Multiple Myeloma

Recruiting at 29 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Disqualifiers: CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

117 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine a safe dose of a new drug combination for individuals with relapsed or hard-to-treat multiple myeloma, a type of blood cancer. The trial tests the main drug, BMS-986393, alongside other treatments such as alnuctamab (ALNUC), mezigdomide, iberdomide, and elranatamab. Individuals who have undergone at least one other treatment for their multiple myeloma but still require assistance might be suitable candidates. 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 this new treatment.

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 the treatments in this study appear promising in terms of safety. Alnuctamab, combined with BMS-986393, is being tested to determine a safe and comfortable dose. Although detailed safety data for this combination is not yet available, studies on similar treatments suggest they are generally well-tolerated.

Mezigdomide, another treatment in the study, has been tested in other trials and demonstrated a manageable safety profile. Patients in these studies often tolerated the treatment well, with side effects similar to those seen in other multiple myeloma treatments.

Iberdomide, when combined with other drugs in past studies, showed a safety profile that met expectations. It was generally safe for patients who had already tried many other treatments.

Elranatamab has been used in special cases for patients with no other options. In these situations, it demonstrated effectiveness against the disease and had a manageable safety profile.

Overall, these treatments are in early testing stages, meaning they are still under study to ensure safety. Previous studies suggest they are generally well-tolerated, but side effects can still occur. Participants should discuss potential risks and benefits with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they introduce novel combinations targeting this complex blood cancer. Unlike traditional treatments like proteasome inhibitors or immunomodulatory drugs, BMS-986393, combined with other agents like Alnuctamab, Mezigdomide, and Iberdomide, offers a fresh approach. BMS-986393 works by enhancing the immune system's ability to recognize and attack cancer cells. Each combination aims to harness different pathways, potentially leading to more effective and personalized treatment strategies. This innovative approach could offer new hope for patients who have exhausted standard options.

What evidence suggests that this trial's treatments could be effective for relapsed and/or refractory multiple myeloma?

This trial will evaluate various novel drug combinations for multiple myeloma. Research has shown that BMS-986393, a type of CAR T-cell therapy, may help treat multiple myeloma by targeting specific proteins on cancer cells. In this trial, participants may receive BMS-986393 in combination with different investigational drugs.

Arm A will study BMS-986393 combined with Alnuctamab, which aids the immune system in fighting cancer by focusing on BCMA, a protein often found on myeloma cells. Arm B will evaluate BMS-986393 with Mezigdomide, and Arm C will test BMS-986393 with Iberdomide. Both Mezigdomide and Iberdomide belong to a group called cereblon E3 ligase modulators, which help break down proteins that cancer cells need to grow. Arm D will explore BMS-986393 combined with Elranatamab, which has demonstrated better survival rates in real-world settings compared to other treatments, with an average survival time of 10.1 months. These experimental treatments are being studied for their potential to offer new options for people with relapsed or hard-to-treat multiple myeloma. ^{1 2 3 4 6}

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 must have had at least one but not more than three prior treatments and be in good physical condition. People can't join if their cancer has spread to the brain or they have other health issues that could affect the study results.

Inclusion Criteria

I have multiple myeloma that has come back or didn't respond to treatment, and I've had 1-3 prior treatments.

I am fully active or can carry out light work.

My multiple myeloma can be measured.

Exclusion Criteria

My multiple myeloma has affected or previously affected my brain or spinal cord.

You have a health condition that could make it hard to understand the study results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986393 in combination with either alnuctamab, mezigdomide, or iberdomide to establish a safe and tolerable dose

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alnuctamab
• BMS-986393
• Iberdomide
• Mezigdomide

Trial Overview The trial is testing BMS-986393 combined with alnuctamab, mezigdomide, and iberdomide to find a safe dose for patients whose multiple myeloma has relapsed or isn't responding to treatment.

How Is the Trial Designed?

Group I: Arm D: BMS-986393 + Elranatamab Experimental Treatment 2 Interventions

Group II: Arm C: BMS-986393 + Iberdomide Experimental Treatment 2 Interventions

Group III: Arm B: BMS-986393 + Mezigdomide Experimental Treatment 2 Interventions

Group IV: Arm A: BMS-986393 + Alnuctamab Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Lead Sponsor

Trials

19

Recruited

3,100+

Published Research Related to This Trial

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 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]

Immunomodulatory drugs (IMiDs) like lenalidomide and pomalidomide have significantly improved outcomes for patients with multiple myeloma, being effective in various treatment settings including newly diagnosed and relapsed cases.

The mechanism of action for IMiDs involves binding to cereblon, which regulates the ubiquitination of important transcription factors, enhancing their therapeutic effects while also raising concerns about potential risks for secondary malignancies and thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience. Holstein, SA., McCarthy, PL.[2018]

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]

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]

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]

Cereblon-targeting immunomodulatory agents like lenalidomide and pomalidomide are crucial in treating Multiple Myeloma due to their ability to enhance anti-tumor effects and work well with other therapies.

Next-generation cereblon E3 ligase modulators, such as iberdomide and CC-92480, are being developed to improve treatment outcomes, highlighting the importance of understanding drug mechanisms and patient-specific factors in creating effective combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing next generation immunomodulatory drugs and their combinations in multiple myeloma. Thakurta, A., Pierceall, WE., Amatangelo, MD., et al.[2021]

Novel cereblon E3 ligase modulators (CELMoDs) show promise for treating relapsed or refractory multiple myeloma (RRMM), particularly in patients resistant to lenalidomide, by enhancing degradation efficiency and kinetics.

CC-92480 is the first CELMoD to enter clinical development, specifically designed for rapid protein degradation, which may improve treatment outcomes for patients with RRMM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma. Hansen, JD., Correa, M., Nagy, MA., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06121843

NCT06121843 | A Study to Evaluate the Safety ... The purpose of this study is to establish a safe and tolerable dose of arlocabtagene autoleucel (BMS-986393) in combinations with alnuctamab, mezigdomide, ...

2. news.bms.com news.bms.com/news/details/2022/Bristol-Myers-Squibb-Announces-First-Disclosures-and-New-Data-at-ASH-2022-Demonstrating-Commitment-to-Raising-Standards-in-Treatment-Through-Broad-Multiple-Myeloma-Portfolio/default.aspx

Corporate news details Bristol Myers Squibb (NYSE: BMY) today announced the first disclosure of results and presentation of new research from its multiple myeloma portfolio.

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/433715

A Study to Evaluate the Safety, Effectiveness and Tolerable ... The purpose of this study is to establish a safe and tolerable dose of BMS-986393 in combinations with alnuctamab, mezigdomide, ...

4. myeloma.org myeloma.org/sparkcures/trial/1795/NCT06121843

CA088-1005 - Clinical Trial The purpose of this study is to establish a safe and tolerable dose of BMS-986393 in combinations with alnuctamab, mezigdomide, and iberdomide in participants ...

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

Alnuctamab Myeloma Trials CC-93269 is a T-cell bi-specific antibody targeting both BCMA and CD3 in patients with multiple myeloma. ... Results: Of 73 pts treated with SC ALNUC in ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20578640

Clinical Trials The purpose of this study is to establish a safe and tolerable dose of BMS-986393 in combinations with alnuctamab, mezigdomide, and iberdomide ...