Mezigdomide Combo vs. Pomalidomide Combo for Multiple Myeloma

(SUCCESSOR-1 Trial)

Recruiting at 535 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Celgene

Must not be taking: Mezigdomide, Pomalidomide

Disqualifiers: Progression on proteasome inhibitors, 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

810 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two different medication combinations to determine which works better for people with relapsed or refractory multiple myeloma, a type of blood cancer that has returned or resisted treatment. The trial compares the effectiveness and safety of a new drug combination, mezigdomide (also known as CC-92480) with bortezomib and dexamethasone, against an existing combination, pomalidomide with bortezomib and dexamethasone. It targets those who have undergone multiple myeloma treatments before, especially if they have tried lenalidomide but need a new option. Participants should have measurable signs of the disease and have shown at least some response to past treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 shows that both treatment combinations in this trial have been studied for safety in people with multiple myeloma, a type of blood cancer.

For the mezigdomide combination (MeziVd), studies have found a manageable safety profile. While side effects occurred, they were generally tolerable. The combination showed promise even in patients who had undergone many treatments before, indicating it is safe enough for further testing.

The pomalidomide combination (PVd) is also considered safe. One study showed it was well-tolerated, with a good safety record in newly diagnosed patients. However, it did not work for as long as hoped.

Both treatment sets have demonstrated they can be used without causing major safety issues in people with this type of cancer. This is promising for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for multiple myeloma, which typically involves treatments like pomalidomide, the investigational drug mezigdomide offers a new approach by potentially enhancing the immune response against cancer cells. Researchers are excited about mezigdomide because it promises a novel mechanism of action that might more effectively target and destroy myeloma cells, possibly improving outcomes for patients. Additionally, this new combination with bortezomib and dexamethasone could offer a more potent therapeutic option with the potential for better efficacy and tolerability compared to existing regimens.

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

This trial will compare two treatment combinations for relapsed or refractory multiple myeloma. One group of participants will receive the combination of mezigdomide, bortezomib, and dexamethasone, called MeziVd. Studies have shown that MeziVd holds promise for treating this type of blood cancer, with patients responding well and experiencing manageable side effects. Another group will receive the combination of pomalidomide, bortezomib, and dexamethasone, known as PVd. PVd has been a standard treatment for some time and remains effective and safe, working well even for patients who did not respond to previous treatments like lenalidomide. Both treatment options are effective, but ongoing research in this trial aims to determine which combination works better for patients. ^{1 2 3 4 6}

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 people with Multiple Myeloma who've had 1-3 previous treatments and were previously treated with lenalidomide. They must have measurable disease, responded at least minimally to past therapy, and not have had a poor reaction or no response to bortezomib. Those who progressed on proteasome inhibitors recently or have been treated with mezigdomide/pomalidomide can't join.

Inclusion Criteria

I have had 1 to 3 treatments for my myeloma.

M-protein ≥ 0.5 grams per deciliter (g/dL) by serum protein electrophoresis (sPEP) or M-protein ≥ 200 milligrams (mg) per 24-hour urine collection by urine protein electrophoresis (uPEP) or serum free light chain (sFLC) levels > 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio for participants without measurable disease in sPEP or uPEP

I have shown improvement after receiving treatment for myeloma.

Exclusion Criteria

I stopped using bortezomib due to side effects or did not respond well to it.

My condition worsened during or soon after my last proteasome inhibitor treatment, but not with low-frequency bortezomib.

I have been treated with mezigdomide or pomalidomide before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Mezigdomide (CC-92480), Bortezomib and Dexamethasone (MEZIVd) or Pomalidomide, Bortezomib and Dexamethasone (PVd) for relapsed or refractory multiple myeloma

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

• Bortezomib
• CC-92480
• Dexamethasone
• Pomalidomide

Trial Overview The study compares two drug combinations for relapsed/refractory Multiple Myeloma: Mezigdomide with Bortezomib and Dexamethasone (MeziVd) versus Pomalidomide with the same additional drugs (PVd). It aims to see which combo works better after prior therapies including lenalidomide.

How Is the Trial Designed?

Group I: PVd (pomalidomide, bortezomib and dexamethasone) Experimental Treatment 3 Interventions

Group II: MeziVd (mezigdomide, bortezomib and dexamethasone) Experimental Treatment 3 Interventions

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

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

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

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

Pomalidomide is a new immunomodulatory drug (IMiD) that has shown more potent anti-myeloma activity compared to existing IMiDs like thalidomide and lenalidomide, with a similar safety profile.

In clinical trials, pomalidomide combined with low-dose dexamethasone has demonstrated effectiveness in myeloma patients who are resistant to other treatments, leading to its accelerated approval by the FDA and EMA as a new strategy for relapsed and refractory myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide for the treatment of relapsed-refractory multiple myeloma: a review of biological and clinical data. Offidani, M., Corvatta, L., Caraffa, P., et al.[2014]

Pretomanid is an effective drug for treating pulmonary extensive drug-resistant tuberculosis (TB) as part of the BPaL regimen, which also includes bedaquiline and linezolid, and it works by inhibiting mycolic acid synthesis, leading to bacterial cell death.

While pretomanid has shown promising results and was approved by the FDA in August 2019, it can cause side effects like peripheral neuropathy and increased liver enzymes, and further research is needed to understand its effects in children, the elderly, and those with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretomanid: The latest USFDA-approved anti-tuberculosis drug. Deb, U., Biswas, S.[2021]

Pomalidomide, in combination with dexamethasone, significantly improves progression-free survival in adult patients with relapsed and refractory multiple myeloma, with a median of 15.7 weeks compared to 8.0 weeks for high-dose dexamethasone alone, based on a phase III study with previously treated patients.

Common side effects of pomalidomide include anemia, neutropenia, and thrombocytopenia, with a notable risk of teratogenic effects, highlighting the need for careful monitoring and management of adverse reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European medicines agency review of pomalidomide in combination with low-dose dexamethasone for the treatment of adult patients with multiple myeloma: summary of the scientific assessment of the committee for medicinal products for human use. Hanaizi, Z., Flores, B., Hemmings, R., et al.[2018]

The combination of pretomanid (PMD) and bedaquiline (BDQ) with linezolid (LZD) showed strong sterilizing activity against tuberculosis (TB) in a murine model, comparable to a previously tested combination with sutezolid (SZD) and superior to first-line treatments.

Adding pyrazinamide (PZA) to the BDQ+PMD+LZD regimen further enhanced its effectiveness, suggesting that these novel combinations could lead to safer and shorter treatment options for drug-resistant TB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contribution of Oxazolidinones to the Efficacy of Novel Regimens Containing Bedaquiline and Pretomanid in a Mouse Model of Tuberculosis. Tasneen, R., Betoudji, F., Tyagi, S., et al.[2020]

Pretomanid is an oral medication developed for treating tuberculosis (TB) and has been approved in the USA as part of the BPaL regimen for adults with extensively drug-resistant (XDR) or treatment-intolerant multidrug-resistant (MDR) TB.

The development of pretomanid involved collaboration with the Global Alliance for TB Drug Development and is now licensed for manufacturing by Mylan, highlighting its importance in addressing TB in both low- and middle-income countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretomanid: First Approval. Keam, SJ.[2020]

In a study of 385 Mycobacterium tuberculosis isolates in Taiwan, 4.7% showed mutations in the pncA gene associated with pyrazinamide resistance, and 7.0% had mutations in gyrA or gyrB linked to fluoroquinolone resistance, indicating a notable prevalence of drug resistance.

The presence of pncA and gyrA/gyrB mutations was significantly associated with more severe forms of tuberculosis, such as MDR-TB, highlighting the importance of routine susceptibility testing for pyrazinamide and fluoroquinolones to inform effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic surveillance and outcomes of pyrazinamide and fluoroquinolones-resistant tuberculosis in Taiwan. Huang, HT., Lin, WH., Chan, TH., et al.[2023]

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]

In a study of 85 newly diagnosed multiple myeloma patients, a high-dose bortezomib regimen (1.6 mg/m2) resulted in a significantly higher complete response rate (43.6%) compared to a low-dose regimen (1.3 mg/m2) which had a response rate of only 12.8%.

While the high-dose regimen showed improved efficacy, particularly in younger patients and those with advanced disease, it was associated with a higher incidence of severe diarrhea, leading to more dose reductions in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients. Li, F., Yao, FS., Zhu, XJ., et al.[2021]

Pomalidomide is a powerful second-generation treatment for multiple myeloma that has shown more effective anti-myeloma activity compared to earlier drugs like thalidomide and lenalidomide, especially in patients who are resistant to those treatments.

In clinical trials, combining pomalidomide with low-dose dexamethasone resulted in better patient responses and survival rates compared to using high-dose dexamethasone or pomalidomide alone, making it a promising option for patients with limited treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pomalidomide in the treatment of relapsed and refractory multiple myeloma]. Roziaková, L., Mistrík, M., Bátorová, A.[2019]

A new procedure was developed to measure 2-ethyl-2-phenylmalonamide levels in the serum of epilepsy patients taking primidone, achieving a sensitivity limit of 1.0 mg/L and demonstrating high precision with low variability in measurements.

In patients co-medicated with phenytoin, the mean steady-state concentration of primidone was significantly higher compared to those also taking carbamazepine, indicating that drug interactions may affect primidone levels in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring 2-ethyl-2-phenylmalonamide in serum by gas-liquid chromatography: application to retrospective study in epilepsy patients dosed with primidone. Haidukewych, D., Rodin, EA.[2019]

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[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. 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.

3. 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, ...

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

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 tested, with no ...

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

6. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-0719.html

A phase 3, two-stage,randomized, multicenter, open-label ... The purpose of this study is to compare the efficacy and safety of mezigdomide (CC-92480), bortezomib and dexamethasone (MeziVd) versus pomalidomide, bortezomib ...