CC-92480 + Other Drugs for Multiple Myeloma

Recruiting at 26 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bristol-Myers Squibb

Must not be taking: Investigational agents

Disqualifiers: CNS involvement, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CC-92480 to determine its safety and effectiveness for people with multiple myeloma, a type of blood cancer that has returned or is not responding to treatment. Researchers aim to assess how well CC-92480 works when combined with other drugs. The trial seeks participants whose multiple myeloma has returned after treatment or is not responding to existing therapies. Participants must have noticeable symptoms of the disease to qualify. 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.

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 used any systemic anti-myeloma drug therapy within 14 days before starting the study treatment.

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

Research shows that CC-92480, when combined with other drugs, has delivered promising results in earlier studies. Patients with difficult-to-treat multiple myeloma, a type of blood cancer, participated in these studies. The treatment was generally well-tolerated by these patients.

Some side effects, common in cancer treatments, were noted but mostly manageable. Researchers have tested the treatment enough in humans to understand its safety. While side effects may occur, the potential benefits of using CC-92480 with other drugs make further exploration worthwhile.

So far, evidence suggests that CC-92480 could be a safe option for patients whose multiple myeloma has not responded to other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CC-92480 for multiple myeloma because it introduces a novel mechanism of action compared to current treatments like proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Unlike these standard options, CC-92480 is a cereblon E3 ligase modulator (CELMoD), which enhances the degradation of specific proteins to inhibit cancer cell growth. This unique approach not only targets cancer cells more precisely but also has the potential to overcome resistance seen with existing therapies. By offering a different pathway to attack multiple myeloma, CC-92480 could significantly improve outcomes for patients who have limited options.

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

Research has shown that CC-92480, also known as mezigdomide, holds promise for treating multiple myeloma. In this trial, participants may receive CC-92480 combined with other drugs. Earlier studies demonstrated that CC-92480, when used with dexamethasone, was effective for patients who had tried many other treatments. CC-92480 works by breaking down certain proteins in cancer cells, causing them to die. Early evidence also suggests that combinations with mezigdomide could be beneficial, encouraging further research. This treatment offers hope for those with relapsed or hard-to-treat multiple myeloma, where other options may not have worked. ^{1 3 6 7 8}

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 adults with Multiple Myeloma that has come back or didn't respond to treatment. They must have measurable disease, be in good physical condition (ECOG PS of 0 or 1), and not suitable for other effective treatments. Participants can't join if they've had certain prior therapies, recent stem-cell transplants, CNS involvement by MM, recent SARS-CoV-2 infection, major surgery, radiation therapy, anti-myeloma drugs or investigational agents within specific time frames.

Inclusion Criteria

My multiple myeloma has worsened despite treatment.

My multiple myeloma hasn't responded to, or I can't tolerate, standard treatments.

Agree to follow the CC-92480 Pregnancy Prevention Plan (PPP)

Exclusion Criteria

I have previously been treated with CC-92480, tazemetostat, BMS-986158, or trametinib.

I haven't had major surgery, certain therapies, or a COVID-19 vaccine recently.

I have had a stem-cell transplant from a donor or my own within the last 12 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Participants receive varying doses of CC-92480 in combination with other treatments to determine the optimal dose

8-12 weeks

Dose Expansion

Participants receive the optimal dose of CC-92480 in combination with other treatments to further assess safety and efficacy

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986158
• CC-92480
• Dexamethasone
• Tazemetostat
• Trametinib

Trial Overview The study tests the safety and effectiveness of CC-92480 (BMS-986348) combined with other drugs like BMS-986158, Trametinib, Dexamethasone and Tazemetostat in treating Relapsed/Refractory Multiple Myeloma. It aims to find out how well these combinations work together.

How Is the Trial Designed?

Group I: Part 2 Arm G: Dose Expansion Experimental Treatment 3 Interventions

Group II: Part 2 Arm E: Dose Expansion Experimental Treatment 3 Interventions

Group III: Part 1 Arm C: Dose Finding Experimental Treatment 3 Interventions

Group IV: Part 1 Arm B: Dose Finding Experimental Treatment 3 Interventions

Group V: Part 1 Arm A: Dose Finding Experimental Treatment 3 Interventions

Group VI: Part 2 Arm D: Dose Expansion Active Control 2 Interventions

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

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]

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]

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]

A sensitive method was developed to measure CC-92480 levels in rat plasma, showing excellent accuracy and reliability, which is crucial for understanding its pharmacokinetics.

CC-92480 demonstrated a high oral bioavailability of over 63%, and its metabolic pathways were identified, indicating potential routes for drug metabolism that could inform future studies on its efficacy in treating myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, bioavailability and metabolism of CC-92480 in rat by liquid chromatography combined with electrospray ionization tandem mass spectrometry. You, W., Pang, J.[2021]

Cereblon (CRBN) is a key target for thalidomide and its derivatives, which are known as immunomodulatory drugs (IMiDs), including lenalidomide and pomalidomide, highlighting their role in modulating CRBN activity.

Recent structural analyses have shown that IMiDs uniquely control the degradation of specific transcription factors through the CRBN-CRLA ubiquitin ligase pathway, suggesting a targeted mechanism of action that is particularly relevant for treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Thalidomide, cereblon and multiple myeloma]. Ogura, T.[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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303194

Mezigdomide plus Dexamethasone in Relapsed and ... The all-oral combination of mezigdomide plus dexamethasone showed promising efficacy in patients with heavily pretreated multiple myeloma.

2. multiplemyelomahub.com multiplemyelomahub.com/medical-information/celmods-for-the-treatment-of-mm-latest-clinical-trial-data

CELMoDs for the treatment of MM: Latest clinical trial data Here, we summarize the latest clinical trial data from studies evaluating the novel CELMoDs, iberdomide and mezigdomide, for the treatment ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06048250

Study Details | NCT06048250 | Mezigdomide (CC-92480) ... CC-92480 works by binding to a protein called CRBN that triggers the breakdown of proteins: Ikaros and Aiolos, leading to cell death in multiple myeloma cells.

4. onclive.com onclive.com/view/preliminary-efficacy-safety-data-drive-further-exploration-of-mezigdomide-based-combinations-in-r-r-myeloma

Preliminary Efficacy, Safety Data Drive Further Exploration ... Siegel, MD, PhD, discusses early safety and efficacy data that support further development of mezigdomide-based combinations in multiple myeloma

5. investors.karyopharm.com investors.karyopharm.com/2023-10-30-Karyopharm-Announces-Clinical-Trial-Collaboration-with-Bristol-Myers-Squibb-to-Evaluate-Novel-CELMoD-TM-Agent-CC-92480-Mezigdomide-in-Combination-with-Selinexor-in-Patients-with-Relapsed-Refractory-Multiple-Myeloma

92480 Mezigdomide in Combination with Selinexor ... This trial will evaluate mezigdomide in combination with selinexor doses of either 40mg or 60mg plus dexamethasone in patients who have prior exposure to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05372354

NCT05372354 | A Study to Evaluate Safety, Drug Levels ... The purpose of this study is to assess the safety, tolerability and preliminary effectiveness of CC-92480 (BMS-986348) in novel therapeutic combinations for the ...

7. bmsstudyconnect.com bmsstudyconnect.com/cz/en/clinical-trials/NCT03374085.html

A Safety, PK and Efficacy Study of CC-92480 Monotherapy ... A safety, PK and efficacy study of CC-92480 monotherapy and in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma (RRMM)

8. bmsstudyconnect.com bmsstudyconnect.com/ca/en/clinical-trials/NCT05372354.html

study connect - BMS Clinical Trials The purpose of this study is to assess the safety, tolerability and preliminary effectiveness of CC-92480 (BMS-986348) in novel therapeutic ...