CC-92480 + Standard Treatments for Multiple Myeloma

Not currently recruiting at 105 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Celgene

Must not be taking: Immunosuppressants

Disqualifiers: Plasma cell leukemia, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CC-92480, a cereblon modulator, for individuals with multiple myeloma, a type of blood cancer. It evaluates the safety and effectiveness of CC-92480 when combined with standard treatments like bortezomib, carfilzomib, and dexamethasone. Participants will join different groups to assess the effectiveness of these combinations. Those with a documented diagnosis of multiple myeloma, measurable disease, and disease progression after previous treatments may be suitable for this study. As a Phase 1, Phase 2 trial, the study aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you have not taken immunosuppressive medication within the last 14 days before starting the study treatment. Other specific medication requirements are not mentioned, so it's best to discuss your current medications with the trial team.

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

A previous study combined CC-92480, also known as mezigdomide, with dexamethasone and demonstrated a promising safety profile. Patients with multiple myeloma tolerated the treatment well, with manageable side effects. When combined with daratumumab and dexamethasone, the safety results remained positive, with few serious side effects reported, suggesting the combination is generally safe.

Early data on combinations with isatuximab and elotuzumab also indicate good safety, as the treatment did not cause many severe reactions, making it a viable option for further testing. For combinations with bortezomib and carfilzomib, the side effects were manageable, meaning they were not too severe or unexpected.

In summary, CC-92480, when used with various standard treatments, has shown a safety profile that supports continued research. Participants generally tolerated these combinations well, with manageable side effects across the board. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CC-92480 for treating multiple myeloma because it represents a novel approach compared to existing therapies. Unlike traditional treatments, which often focus on destroying cancer cells directly, CC-92480 is a cereblon E3 ligase modulator (CELMoD) that promotes the degradation of proteins crucial for myeloma cell survival and proliferation. This new mechanism of action could potentially overcome resistance to standard therapies like bortezomib and lenalidomide. Additionally, CC-92480 is being tested in combination with other powerful drugs such as daratumumab and isatuximab, potentially enhancing its effectiveness and offering new hope for patients with resistant forms of multiple myeloma.

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

Research shows that CC-92480, also known as mezigdomide, holds promise for treating multiple myeloma. This trial will administer different combinations of CC-92480 with standard treatments. One treatment arm will test CC-92480 with bortezomib and dexamethasone, which studies have shown to provide significant benefits. Another arm will evaluate CC-92480 with carfilzomib and dexamethasone, particularly effective for patients who have undergone many treatments. Additionally, CC-92480 with daratumumab and dexamethasone is being tested for its effectiveness in fighting cancer cells. Early data shows potential for the combination of CC-92480 with elotuzumab and dexamethasone. Lastly, another arm will study CC-92480 with isatuximab and dexamethasone, with initial results suggesting effectiveness. These findings support that CC-92480, in various combinations, could be a strong option for those battling multiple myeloma. ^{1 6 7 8 9}

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 who've seen their cancer grow despite treatment and responded at least once to prior therapy. They should be fairly active and able to care for themselves (ECOG score of 0-2). People can't join if they have myeloma in the brain, took strong immune drugs recently, or have certain other blood disorders or uncontrolled conditions like high blood pressure.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I have multiple myeloma with measurable disease and it has worsened after treatment but I responded to at least one prior treatment.

Exclusion Criteria

I have not taken immunosuppressive medication in the last 14 days.

Other protocol-defined inclusion/exclusion criteria apply

My myeloma has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CC-92480 in combination with standard treatments such as bortezomib, dexamethasone, daratumumab, carfilzomib, isatuximab, or elotuzumab over 21-day or 28-day cycles

6-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Carfilzomib
• CC-92480
• Daratumumab
• Dexamethasone
• Elotuzumab
• Isatuximab

Trial Overview The study tests CC-92480 combined with standard myeloma treatments (like Isatuximab, Bortezomib) to see how safe it is and if it works against cancer that's come back or didn't respond well before. Participants will receive different combinations based on which group they're assigned to.

How Is the Trial Designed?

Group I: Subcohort E3: CC-92480 with daratumumab and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at RP2D administered over a 28-day cycle Either Intravenous (IV) DARA administered at a dose of 16 mg/kg or Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle

Group II: Subcohort E2: CC-92480 with daratumumab and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at RP2D administered over a 21-day cycle from Cycle 1 to Cycle 8 and over a 28-day cycle from Cycle 9 onwards Either Intravenous (IV) DARA administered at a dose of 16 mg/kg or Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight, administered over a 21-day cycle from Cycle 1 to Cycle 8 and over a 28-day cycle from Cycle 9 onwards

Group III: Subcohort E1: CC-92480 with daratumumab and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at RP2D administered over a 28-day cycle Either IV DARA administered at a dose of 16 mg/kg or SC DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle

Group IV: Subcohort B3: CC-92480 with daratumumab and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at specified cohort B dose administered over a 28-day cycle Either Intravenous (IV) DARA administered at a dose of 16 mg/kg or Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle

Group V: Subcohort B2: CC-92480 with daratumumab and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at specified cohort dose administered over a 21-day cycle from Cycle 1 to Cycle 8 and over a 28-day cycle from Cycle 9 onwards Either Intravenous (IV) DARA administered at a dose of 16 mg/kg or Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight, administered over a 21-day cycle from Cycle 1 to Cycle 8 and over a 28-day cycle from Cycle 9 onwards

Group VI: Subcohort B1: CC-92480 with daratumumab and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at specified cohort dose administered over a 28-day cycle Either Intravenous (IV) DARA administered at a dose of 16 mg/kg or Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle

Group VII: Cohort K: CC-92480 with isatuximab and dexamethasone Experimental Treatment 3 Interventions

Group VIII: Cohort J: CC-92480 with elotuzumab and dexamethasone Experimental Treatment 3 Interventions

Group IX: Cohort I: CC-92480 with isatuximab and dexamethasone Experimental Treatment 3 Interventions

Group X: Cohort H: CC-92480 with elotuzumab and dexamethasone Experimental Treatment 3 Interventions

Group XI: Cohort G: CC-92480 with bortezomib and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at RP2D administered over a 21-day cycle Subcutaneous bortezomib 1.3 mg/m2 administered over a 21-day cycle up to Cycle 6 Oral dexamethasone 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle up to Cycle 6

Group XII: Cohort F: CC-92480 with carfilzomib and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at RP2D administered over a 28-day cycle Intravenous (IV) carfilzomib 20 mg/m2 then 56 mg/m2 administered over a 28-day cycle Oral/IV dexamethasone 40 mg/day (20 mg/day for subjects > 75 years old) administered over a 28-day cycle

Group XIII: Cohort D: CC-92480 with bortezomib and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at RP2D administered over a 21-day cycle Subcutaneous bortezomib 1.3 mg/m2 administered over a 21-day cycle Oral dexamethasone 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle in the first 8 cycles and on days 1, 2, 8 and 9 after Cycle 8

Group XIV: Cohort C: CC-92480 with carfilzomib and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at specified cohort C dose administered over a 28-day cycle Intravenous (IV) carfilzomib 20 mg/m2 then 56 mg/m2 administered over a 28-day cycle Oral/IV dexamethasone 40 mg/day (20 mg/day for subjects > 75 years old) administered over a 28-day cycle

Group XV: Cohort A: CC-92480 with bortezomib and dexamethasone Experimental Treatment 3 Interventions

Oral CC-92480 at specified cohort A dose administered over a 21-day cycle Subcutaneous bortezomib 1.3 mg/m2 administered over a 21-day cycle Oral dexamethasone 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle in the first 8 cycles and on days 1, 2, 8 and 9 after Cycle 8

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

Top Products

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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 II trial involving 300 patients, carfilzomib combined with cyclophosphamide and dexamethasone (KCd) showed a higher overall response rate (84.0%) compared to bortezomib with the same regimen (VCd, 68.1%), indicating that KCd is at least as effective as VCd for treating myeloma.

Carfilzomib maintenance therapy significantly improved progression-free survival, with a median of 11.9 months compared to 5.6 months for those not receiving maintenance, highlighting its efficacy in prolonging treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib or bortezomib in combination with cyclophosphamide and dexamethasone followed by carfilzomib maintenance for patients with multiple myeloma after one prior therapy: results from a multicenter, phase II, randomized, controlled trial (MUKfive). Yong, KL., Hinsley, S., Auner, HW., et al.[2021]

Bortezomib is the first proteasome inhibitor approved for treating multiple myeloma (MM), showing significant survival benefits as a mono-therapy and in combination with other drugs.

The neurotoxicity associated with bortezomib has been reduced through subcutaneous administration and weekly dosing, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib for the treatment of multiple myeloma. Grosicki, S., Barchnicka, A., Jurczyszyn, A., et al.[2015]

In a study of 16 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone resulted in a high clinical response rate of 87.5%, with 6 patients achieving near complete response.

The treatment was associated with manageable side effects, primarily gastrointestinal issues and thrombocytopenia, which were alleviated with supportive care, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bortezomib in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma]. Yuan, ZG., Hou, J., Zhou, F., et al.[2015]

In a phase 3 study involving 466 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib, dexamethasone, and daratumumab (KdD) significantly improved progression-free survival compared to carfilzomib and dexamethasone alone (Kd), with a hazard ratio of 0.63, indicating a 37% reduction in the risk of disease progression.

Despite a higher incidence of grade 3 or higher adverse events in the KdD group (82%) compared to the Kd group (74%), the overall safety profile was considered favorable, with similar rates of treatment discontinuation due to adverse events in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Dimopoulos, M., Quach, H., Mateos, MV., et al.[2020]

The KD-PACE regimen, which includes carfilzomib instead of bortezomib, was found to be a feasible bridging therapy for 52 patients with relapsed or refractory multiple myeloma, showing no unexpected toxicities.

Patients who were successfully bridged to autologous or allogenic stem cell transplants or clinical trials had significantly better progression-free survival (8.3 months) and overall survival (16.7 months) compared to those who were not bridged (2.3 months and 4.3 months, respectively).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KD-PACE Salvage Therapy for Aggressive Relapsed Refractory Multiple Myeloma, Plasma Cell Leukemia and Extramedullary Myeloma. Alsouqi, A., Khan, M., Dhakal, B., et al.[2022]

In a study involving 929 patients with relapsed or refractory multiple myeloma, carfilzomib combined with dexamethasone significantly improved median progression-free survival (18.7 months) compared to bortezomib with dexamethasone (9.4 months), indicating greater efficacy of carfilzomib.

While both treatments had serious adverse events, carfilzomib was associated with a higher rate of serious adverse events (48%) compared to bortezomib (36%), suggesting that while carfilzomib may be more effective, it also carries a higher risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Dimopoulos, MA., Moreau, P., Palumbo, A., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1025/531470/Mezigdomide-MEZI-Plus-Dexamethasone-DEX-and

Mezigdomide (MEZI) Plus Dexamethasone (DEX) and ... Conclusions: With longer follow-up, MeziVd and MeziKd in RRMM confirmed promising efficacy and a manageable safety profile at all dose levels ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05519085

NCT05519085 | A Study to Evaluate Mezigdomide, ... The purpose of this study is to compare the efficacy and safety of mezigdomide (CC-92480), bortezomib and dexamethasone (MeziVd) versus pomalidomide, ...

3. 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.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124037728

Mezigdomide (MEZI) Plus Dexamethasone (DEX) and ... In the phase 1/2 CC-92480-MM-002 trial (NCT03989414), MEZI combined with DEX and BORT (MeziVd) or DEX and CFZ (MeziKd) showed meaningful clinical activity and ...

5. 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 The CC-92480-MM-002 trial (NCT03989414) is a phase I/II, multicenter study evaluating the optimal dosing, safety, and efficacy of mezigdomide in ...

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. 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 ... David S. Siegel, MD, PhD, discusses early safety and efficacy data that support further development of mezigdomide-based combinations in multiple myeloma.

8. 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)

9. 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 ...