Mezigdomide Combo vs. Pomalidomide Combo for Multiple Myeloma

(SUCCESSOR-1 Trial)

Recruiting in Palo Alto (17 mi)

+476 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Celgene

Must not be taking: Mezigdomide, Pomalidomide

Disqualifiers: Progression on proteasome inhibitors, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing two drug combinations to find out which one is better and safer for patients with multiple myeloma that has come back or not responded to previous treatments. The drugs work together to kill cancer cells by stopping their growth, helping the immune system attack them, and making it harder for them to survive.

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.

What data supports the effectiveness of the drug combination Mezigdomide and Pomalidomide for treating multiple myeloma?

Pomalidomide, when combined with dexamethasone, has shown better responses and longer survival in patients with relapsed and refractory multiple myeloma compared to high-dose dexamethasone alone. Mezigdomide has demonstrated strong anti-cancer activity in preclinical models of multiple myeloma, including those resistant to other treatments. ^{1 2 3 4 5}

Is the Mezigdomide Combo vs. Pomalidomide Combo treatment generally safe for humans?

Pomalidomide, when used with dexamethasone, has shown a favorable safety profile similar to other treatments like thalidomide and lenalidomide, with common side effects being blood-related issues such as low white blood cell count, low platelet count, and anemia. Bortezomib, when combined with other drugs, has also demonstrated significant safety for newly diagnosed multiple myeloma patients. Mezigdomide is a newer drug with promising preclinical results, but specific safety data in humans is not detailed in the provided research. ^{1 3 4 5 6}

What makes the Mezigdomide Combo treatment for multiple myeloma unique?

The Mezigdomide Combo treatment is unique because it combines mezigdomide, a novel cereblon modulator, with other drugs like bortezomib and dexamethasone, potentially offering a new mechanism of action by targeting protein degradation pathways in cancer cells, which may enhance treatment efficacy compared to existing therapies. ^{7 8 9 10 11}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Bortezomib (Proteasome Inhibitor)
• CC-92480 (Other)
• Dexamethasone (Corticosteroid)
• Pomalidomide (Immunomodulatory Agent)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pomalidomide for the treatment of relapsed-refractory multiple myeloma: a review of biological and clinical data. [2014]

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

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. [2022]

3. Czech Republic pubmed.ncbi.nlm.nih.gov

[Pomalidomide in the treatment of relapsed and refractory multiple myeloma]. [2019]

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

Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. [2023]

5. England 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. [2018]

6. Germany 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. [2021]

7. India pubmed.ncbi.nlm.nih.gov

Pretomanid: The latest USFDA-approved anti-tuberculosis drug. [2021]

8. England 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. [2019]

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

Contribution of Oxazolidinones to the Efficacy of Novel Regimens Containing Bedaquiline and Pretomanid in a Mouse Model of Tuberculosis. [2020]

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

Pretomanid: First Approval. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Genetic surveillance and outcomes of pyrazinamide and fluoroquinolones-resistant tuberculosis in Taiwan. [2023]