Mezigdomide + Carfilzomib + Dexamethasone for Multiple Myeloma

(SUCCESSOR-2 Trial)

Recruiting at 401 trial locations

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

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Bristol-Myers Squibb

Must not be taking: Mezigdomide, Carfilzomib

Disqualifiers: Allogeneic transplant, Recent autologous transplant, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called Mezigdomide combined with two other drugs to treat patients whose blood cancer has come back or not responded to previous treatments. The new drug aims to stop cancer cells from growing and spreading.

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.

What data supports the effectiveness of the drug combination Mezigdomide, Carfilzomib, and Dexamethasone for treating multiple myeloma?

Carfilzomib, a key component of the combination, has shown effectiveness in treating multiple myeloma, especially in patients who have relapsed or are resistant to other treatments. Studies have demonstrated that carfilzomib, when used in combination with other drugs like dexamethasone, can significantly prolong the time patients live without their disease getting worse. ^{1 2 3 4 5}

What makes the drug combination of Mezigdomide, Carfilzomib, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because it includes Mezigdomide, a novel cereblon modulator, alongside Carfilzomib, a second-generation proteasome inhibitor, and Dexamethasone, a steroid. This combination aims to enhance the effectiveness of treatment by targeting multiple pathways involved in multiple myeloma, potentially offering benefits over existing therapies that use different drug combinations. ^{1 4 6 7 8}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Carfilzomib (Proteasome Inhibitor)
• CC-92480 (Small Molecule)
• Dexamethasone (Corticosteroid)

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.

Participant Groups

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

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

Carfilzomib is already approved in Canada, Japan for the following indications:

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

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]

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]

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 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]

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]

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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

Carfilzomib boosted combination therapy for relapsed multiple myeloma. [2020]

4. France pubmed.ncbi.nlm.nih.gov

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

5. United States 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. [2020]

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

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

7. 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]

8. Germany 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). [2023]