Mezigdomide + Carfilzomib + Dexamethasone for Multiple Myeloma

(SUCCESSOR-2 Trial)

Recruiting at 408 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Mezigdomide, Carfilzomib

Disqualifiers: Allogeneic transplant, Recent autologous transplant, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

525 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for people with multiple myeloma, a type of blood cancer affecting plasma cells in the bone marrow. Researchers aim to determine if adding Mezigdomide (an experimental treatment) to the current regimen of carfilzomib and dexamethasone is more effective than using carfilzomib and dexamethasone alone. Individuals with multiple myeloma who have undergone at least one prior treatment and experienced disease progression might find this trial suitable. Participants must not have previously received mezigdomide or carfilzomib. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if 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 has shown that the combination of mezigdomide, carfilzomib, and dexamethasone is generally well-tolerated. Previous studies found this treatment effective for patients whose multiple myeloma returned after earlier treatments.

When mezigdomide and dexamethasone were used together, patients demonstrated promising results, even after trying many other treatments. Regarding safety, the combination of mezigdomide, carfilzomib, and dexamethasone has a manageable safety profile. While some side effects may occur, they are usually not severe and can be managed with proper medical care.

Overall, patients have handled the treatment at different dose levels without serious issues. Although side effects may still occur, most people can tolerate the treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple myeloma, like lenalidomide and bortezomib, Mezigdomide (also known as CC-92480) offers a novel approach by targeting proteins for degradation, which could lead to more effective elimination of cancer cells. Researchers are excited about this treatment because it's combined with Carfilzomib and Dexamethasone to potentially enhance its efficacy and overcome resistance seen with current therapies. This combination could offer a new hope for patients, providing a more powerful punch against multiple myeloma with possibly improved outcomes.

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

Research has shown that combining Mezigdomide with dexamethasone yields promising results for patients with multiple myeloma, especially those who have undergone many prior treatments. Mezigdomide attaches more effectively to cereblon, a protein that helps the body fight cancer, enhancing its ability to target cancer cells. In this trial, participants may receive Mezigdomide with carfilzomib and dexamethasone (MeziKd), which has demonstrated good results and manageable side effects in studies. Alternatively, participants may receive the combination of carfilzomib and dexamethasone (Kd), already known to be effective for treating relapsed multiple myeloma. Both treatment options in this trial aim to control the disease and improve patient outcomes. ^{1 2 3 6 7}

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 individuals with multiple myeloma who've had at least one prior treatment, including lenalidomide and an anti-CD38 monoclonal antibody. They should have shown some response to previous treatments and must have disease progression after the last regimen. Those previously treated with mezigdomide or carfilzomib, or recent stem cell transplant recipients cannot participate.

Inclusion Criteria

I have been treated with lenalidomide and an anti-CD38 drug for at least 2 cycles.

I have been diagnosed with multiple myeloma and it can be measured.

I have undergone treatment for myeloma before.

Exclusion Criteria

I have previously been treated with mezigdomide or carfilzomib.

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

Treatment

Participants receive Mezigdomide in combination with Carfilzomib and Dexamethasone or Carfilzomib and Dexamethasone alone

Up to 12 months

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

• Carfilzomib
• CC-92480
• Dexamethasone

Trial Overview The SUCCESSOR-2 study is testing Mezigdomide combined with Carfilzomib and Dexamethasone (MeziKD) against just Carfilzomib and Dexamethasone (Kd). The goal is to see which combination works better for relapsed or refractory multiple myeloma.

How Is the Trial Designed?

Group I: MeziKd (Mezigdomide + Carfilzomib + Dexamethasone) Experimental Treatment 3 Interventions

Group II: Kd (Carfilzomib + Dexamethasone) Active Control 2 Interventions

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

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

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

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]

Carfilzomib, when used in combination with lenalidomide and dexamethasone, significantly prolongs progression-free survival (PFS) by 8.7 months in patients with relapsed multiple myeloma, based on results from the phase III ASPIRE study involving a multinational patient population.

The combination therapy has a manageable safety profile, with low incidences of severe adverse events, suggesting it is a viable treatment option for patients who have received prior therapies, although overall survival data is still pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma. Hoy, SM.[2018]

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]

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 real-world study of 152 patients with relapsed and/or refractory multiple myeloma treated with carfilzomib plus dexamethasone, the overall response rate was 71.1%, indicating that this treatment is effective in a clinical setting.

Patients classified as trial-unfit had significantly shorter progression-free survival (3.6 months) and overall survival (15.0 months) compared to trial-fit patients (7.3 months and 36.8 months, respectively), highlighting the importance of patient fitness in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment outcomes of carfilzomib plus dexamethasone in patients with relapsed and/or refractory multiple myeloma, focusing on the impact of trial-fitness: CAtholic REsearch network for Multiple Myeloma study (CAREMM-2203). Park, SS., Goo, SY., Jeon, YW., et al.[2023]

Carfilzomib is a proteasome inhibitor that effectively treats relapsed and refractory multiple myeloma, showing durable antimyeloma activity with manageable side effects, leading to its approval in several countries including the USA.

Ongoing Phase III studies are exploring carfilzomib's use in earlier treatment stages, which may expand its indications and support regulatory approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib for the treatment of patients with relapsed and/or refractory multiple myeloma. Stewart, AK.[2015]

Carfilzomib is a selective and irreversible proteasome inhibitor that leads to tumor cell growth arrest and apoptosis, making it an effective treatment for multiple myeloma.

Initially approved for advanced cases, carfilzomib is now also used in earlier relapse settings, often in combination with lenalidomide and dexamethasone, showing improved clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib boosted combination therapy for relapsed multiple myeloma. Steiner, RE., Manasanch, EE.[2020]

In the phase I IFM2012-03 study involving 30 elderly patients with newly diagnosed multiple myeloma, the maximum tolerated dose (MTD) of carfilzomib was determined to be 70 mg/m² when administered weekly, with a notable overall response rate of 93.3% and a complete response rate of 46.6%.

The safety profile of weekly carfilzomib was generally acceptable, although there were specific risks of cardiovascular events and other toxicities, particularly in older patients, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Weekly plus Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Multiple Myeloma (IFM 2012-03): A Phase I Trial. Leleu, X., Fouquet, G., Richez, V., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05552976

NCT05552976 | A Study to Evaluate Mezigdomide in ... The purpose of the study is to compare Mezigdomide (CC-92480/BMS-986348) with carfilzomib and dexamethasone (MeziKD) against carfilzomib and dexamethasone (Kd) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06627751

Study Details | NCT06627751 | Mezigdomide, Carfilzomib ... This phase II trial studies how well mezigdomide/carfilzomib/dexamethasone (MeziKD) works in treating patients with multiple myeloma (MM) that has come back ...

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. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper198408.html

Mezigdomide (MEZI) Plus Dexamethasone (DEX) ... Conclusions: With longer follow-up, MeziVd and MeziKd in RRMM confirmed promising efficacy and a manageable safety profile at all dose levels tested, with no ...

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

Mezigdomide for multiple myeloma: a focus on phase 2 ... Mezigdomide, which is not currently approved for the treatment of MM, has higher cereblon binding affinity and greater potency for substrate ...

6. 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 ...

7. myeloma.org myeloma.org/sparkcures/trial/2111/description

Mezigdomide, Carfilzomib, and Dexamethasone This phase II trial studies how well mezigdomide/carfilzomib/dexamethasone (MeziKD) works in treating patients with multiple myeloma (MM) that has come back ...