CC-92480 + Dexamethasone for Multiple Myeloma

Recruiting at 106 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Celgene

Must be taking: Lenalidomide, Pomalidomide, Proteasome inhibitors, CD38 antibody

Must not be taking: Strong CYP3A modulators, Proton-pump inhibitors

Disqualifiers: Dialysis, Cardiac disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 28 days

201 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multi-center, international, Phase 1/2 study to assess the safety, PK and efficacy of CC-92480 monotherapy and in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma (RRMM). All eligible subjects must be previously treated with at least 3 prior regimens including lenalidomide, pomalidomide, a proteasome inhibitor and an anti-CD38 antibody and be refractory to their last line of therapy.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot take strong CYP3A modulators or proton-pump inhibitors within 2 weeks before starting the trial medication.

What data supports the effectiveness of the drug CC-92480 combined with Dexamethasone for treating multiple myeloma?

Research shows that Mezigdomide, a drug similar to CC-92480, has strong anti-cancer effects in multiple myeloma, even in cases resistant to other treatments. Additionally, CC-92480 itself has shown potent activity against multiple myeloma in preclinical studies. ^{1 2 3 4 5}

Is the combination of Mezigdomide (CC-92480) and Dexamethasone safe for humans?

The safety of Mezigdomide (CC-92480) combined with Dexamethasone has been evaluated in clinical settings for multiple myeloma, showing it has potent activity against the disease. However, specific safety data for humans is not detailed in the available research abstracts. ^{1 2 4 5 6}

What makes the drug CC-92480 unique for treating multiple myeloma?

CC-92480, also known as Mezigdomide, is a novel drug that targets cereblon, a protein involved in the growth of multiple myeloma cells, and has shown strong activity even in cases resistant to other similar drugs like lenalidomide and pomalidomide. This makes it a promising option for patients with relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults over 18 with relapsed and refractory multiple myeloma who've had at least 3 prior treatments, including specific medications, and are not responding to their last therapy. They must have measurable disease, meet certain lab value criteria, be able to follow the study plan, and use contraception if of childbearing potential.

Inclusion Criteria

My myeloma worsened within 2 months after my last treatment.

Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

Subject has a significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

I have had a bone marrow transplant from another person.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of CC-92480 monotherapy or in combination with dexamethasone

Up to approximately 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 3 years

Treatment Details

Interventions

• CC-92480
• Dexamethasone

Trial Overview The trial is testing CC-92480 alone and combined with Dexamethasone in patients whose multiple myeloma has returned or resisted treatment. It's an open-label Phase 1/2 study assessing safety, how the body processes the drug (PK), and its effectiveness against this cancer.

Participant Groups

Group I: Administration of CC-92480 monotherapy Experimental Treatment 1 Intervention

Escalating doses of CC-92480 Monotherapy administered according to different dosing schedules

Group II: Administration of CC-92480 in combination with dexamethasone Experimental Treatment 2 Interventions

Part 1: Escalating doses of CC-92480 plus a fixed dose of dexamethasone Part 2: RP2D of CC-92480 in combination with dexamethasone

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

Findings from Research

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]

A sensitive method was developed to measure CC-92480 levels in rat plasma, showing excellent accuracy and reliability, which is crucial for understanding its pharmacokinetics.

CC-92480 demonstrated a high oral bioavailability of over 63%, and its metabolic pathways were identified, indicating potential routes for drug metabolism that could inform future studies on its efficacy in treating myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, bioavailability and metabolism of CC-92480 in rat by liquid chromatography combined with electrospray ionization tandem mass spectrometry. You, W., Pang, J.[2021]

Thalidomide and similar drugs are important treatments for multiple myeloma, as they target cereblon, a protein that plays a crucial role in protein degradation.

By binding to cereblon, these drugs change how the ubiquitin ligase complex works, leading to the destruction of Ikaros and Aiolos, which are key transcription factors needed for the growth of multiple myeloma cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From anecdote to targeted therapy: the curious case of thalidomide in multiple myeloma. Licht, JD., Shortt, J., Johnstone, R.[2021]

Iberdomide combined with dexamethasone demonstrated meaningful clinical activity in heavily pretreated patients with relapsed or refractory multiple myeloma, achieving an overall response rate of 32% in the dose-escalation cohort and 26% in the dose-expansion cohort, indicating its potential effectiveness even in difficult-to-treat cases.

The treatment was generally safe, with a recommended phase 2 dose established at 1.6 mg, although some patients experienced serious adverse events, including neutropenia and infections, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lonial, S., Popat, R., Hulin, C., et al.[2022]

The study identified argonaute 2 (AGO2) as a key cereblon binding partner that is regulated by the immunomodulatory drug lenalidomide, which affects multiple myeloma (MM) cell survival.

Silencing AGO2 in MM cells led to significant cell death, suggesting that targeting AGO2 could be a promising strategy to overcome resistance to IMiDs like lenalidomide in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of the cereblon binding protein argonaute 2 plays an important role for multiple myeloma cell growth and survival. Xu, Q., Hou, YX., Langlais, P., et al.[2020]

Cereblon (CRBN) is a key target for thalidomide and its derivatives, which are known as immunomodulatory drugs (IMiDs), including lenalidomide and pomalidomide, highlighting their role in modulating CRBN activity.

Recent structural analyses have shown that IMiDs uniquely control the degradation of specific transcription factors through the CRBN-CRLA ubiquitin ligase pathway, suggesting a targeted mechanism of action that is particularly relevant for treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Thalidomide, cereblon and multiple myeloma]. Ogura, T.[2020]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, bioavailability and metabolism of CC-92480 in rat by liquid chromatography combined with electrospray ionization tandem mass spectrometry. [2021]

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

From anecdote to targeted therapy: the curious case of thalidomide in multiple myeloma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Expression of the cereblon binding protein argonaute 2 plays an important role for multiple myeloma cell growth and survival. [2020]

6. Japan pubmed.ncbi.nlm.nih.gov

[Thalidomide, cereblon and multiple myeloma]. [2020]