CC-92480 + Standard Treatments for Multiple Myeloma

Recruiting at 95 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

424 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called CC-92480 to see if it can help patients who are already getting standard treatments. The goal is to find out if adding this new drug can make their treatment work better.

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.

What data supports the effectiveness of the drug combination CC-92480 and standard treatments for multiple myeloma?

Research shows that carfilzomib, a component of the treatment, is effective in patients with multiple myeloma, especially those who are resistant to bortezomib, another drug in the treatment. Carfilzomib has been shown to have a higher overall response rate and less neurotoxicity compared to bortezomib, making it a promising option for patients with relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

Is the combination of CC-92480 and standard treatments for multiple myeloma safe for humans?

Carfilzomib, a component of the treatment, is generally well tolerated with minimal nerve-related side effects compared to bortezomib, which can cause more nerve damage. The combination of carfilzomib with other drugs like dexamethasone and daratumumab has shown tolerable safety in patients with relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

What makes the drug CC-92480 combined with standard treatments unique for multiple myeloma?

The combination of CC-92480 with standard treatments for multiple myeloma is unique because it includes a novel drug, CC-92480, which is a cereblon modulator that may enhance the effectiveness of existing therapies like bortezomib and dexamethasone, potentially leading to better outcomes for patients. ^{6 7 8 9 10}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

References

1. Italy 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). [2021]

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

KD-PACE Salvage Therapy for Aggressive Relapsed Refractory Multiple Myeloma, Plasma Cell Leukemia and Extramedullary Myeloma. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Emerging role of carfilzomib in treatment of relapsed and refractory lymphoid neoplasms and multiple myeloma. [2023]

4. England 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. [2020]

5. England 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. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Bortezomib a safe treatment for patients with multiple myeloma and cystic fibrosis. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Proteasome inhibition in multiple myeloma. [2015]

8. China pubmed.ncbi.nlm.nih.gov

[Bortezomib in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma]. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Bortezomib for the treatment of multiple myeloma. [2015]

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

Proteasome inhibition for treatment of multiple myeloma: clinical update. [2015]