Mezigdomide + Talquetamab for Multiple Myeloma

(MAGENTA Trial)

Not yet recruiting at 2 trial locations

Overseen By Andrew J. Yee, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must be taking: Thromboembolism prophylaxis

Must not be taking: Investigational agents

Disqualifiers: Primary refractory disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: Estimated 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, mezigdomide and talquetamab, to determine the optimal dose and schedule for treating relapsed and refractory multiple myeloma—a type of blood cancer that has returned or resisted treatment. The study involves two groups: one will start with talquetamab, and the other will start with mezigdomide. Researchers aim to assess how these drugs affect the cancer. The trial seeks participants who have undergone multiple myeloma treatments but still experience disease progression. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these potentially groundbreaking therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you cannot have had myeloma therapy or investigational drugs within 2 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that talquetamab is effective and manageable for patients with relapsed or refractory multiple myeloma. The FDA recently approved it for patients who have already tried several treatments, indicating that talquetamab is generally well-tolerated in humans.

Early results for mezigdomide show a promising safety profile when combined with other treatments for multiple myeloma. Patients who took mezigdomide reported manageable side effects, meaning it did not cause severe problems for most people.

These findings suggest that both talquetamab and mezigdomide have been tested in people with similar conditions and are considered relatively safe. However, this is a phase 1 trial, which aims to determine the right dosages and potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Mezigdomide and Talquetamab because they offer a novel approach to treating multiple myeloma. Most current treatments for this condition, like lenalidomide and bortezomib, target existing cancer cells, but these new drugs have unique mechanisms of action. Mezigdomide is designed to modulate the immune system by enhancing the body's ability to target cancer cells, while Talquetamab specifically targets a protein called GPRC5D found on multiple myeloma cells. This dual-action approach not only aims to better control the disease but also minimizes damage to healthy cells, potentially reducing side effects compared to traditional therapies.

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

Research has shown that talquetamab is effective for patients with relapsed or hard-to-treat multiple myeloma, with earlier studies finding that 73% of patients responded well to talquetamab. In this trial, participants in Cohort A will initially receive talquetamab and dexamethasone, with mezigdomide added in subsequent cycles. When used with other treatments, mezigdomide has also shown promising results, prompting further research on its use for multiple myeloma. Early data suggest that combinations with mezigdomide can be effective against this type of cancer. Participants in Cohort B will start with mezigdomide and dexamethasone, followed by the addition of talquetamab. Together, these drugs have a strong record of helping patients with difficult-to-treat multiple myeloma. ^{1 2 4 5 6}

Who Is on the Research Team?

Andrew J. Yee, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with relapsed and refractory multiple myeloma, meaning their cancer has returned or didn't respond to treatment. Participants must meet specific health criteria not detailed here.

Inclusion Criteria

I can perform daily activities with little or no assistance.

My platelet count is at least 50,000 and I haven't had platelet transfusions or certain medications in the last week.

My hemoglobin level is at least 8 g/dL.

Exclusion Criteria

I am on low dose steroids for a condition other than myeloma.

I have not undergone plasmapheresis within the last week.

I have previously been treated with a GPRC5D-targeting therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mezigdomide, talquetamab, and dexamethasone in a dose escalation schedule until disease progression or withdrawal

Estimated 1 year

Multiple visits per cycle, including Days 1, 4, 8, 15 for initial cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years post last-dose

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Mezigdomide
• Talquetamab

Trial Overview The study is testing the combination of mezigdomide and talquetamab with dexamethasone in two steps to find the best dose and schedule for treating multiple myeloma. Cohort A gets one drug combo first, then both; Cohort B starts with another combo followed by a gradual increase of talquetamab.

How Is the Trial Designed?

Group I: Cohort B Experimental Treatment 3 Interventions

Cohort B takes place after Cohort A. Pre-phase 7 day cycle: Mezigdomide is administered orally once per day on Days 1-7. Dexamethasone is administered orally on Days 1 and 2. Cycle 1 (28 day cycle): Talquetamab is subcutaneously injected on Day 1, 4, 8, and 15 at a pre-determined escalating dose. Mezigdomide is given orally on days 1-14. Dexamethasone is administered orally as pre-medications before receiving talquetamab. Cycle 2+ (28 day cycle): Talquetamab on Days 1 and 15 of cycles 2-6; then Day 1 of cycles 7-12. Mezigdomide on Days 1-21 of cycles 2+ until disease progression or withdrawal. Dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, 23 of cycles 2-6.

Group II: Cohort A Experimental Treatment 3 Interventions

Cycle 1: Talquetamab and dexamethasone at a pre-determined escalating dose of talquetamab. Talquetamab is subcutaneously injected on Day 1, 4, 8, and 15 of the 28-day cycle. Dexamethasone is administered orally before receiving talquetamab (Days 1, 4, 8, 15). Cycle 2+: Mezigdomide, talquetamab, and dexamethasone Talquetamab is administered on Day 1 and 15 of cycles 2-6 and on Day 1 of cycles 7-12. Mezigdomide is administered orally once per day on days 1-21 of each 28-day cycle starting with cycle 2. This can continue until disease progression or withdrawal. Dexamethasone is administered orally once per week starting on Day 1 of Cycle 2 through cycle 6; the weekly dose will be split into 2 days.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Janssen Research and Development LLC

Collaborator

Trials

1

Recruited

80+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11798766/

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ... The efficacy data showed were overlapping for both dose levels. Efficacy outcomes, assessed according to International Myeloma Working Group ( ...

2. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00385-5/fulltext

Safety and activity of talquetamab in patients with relapsed ... Talquetamab continued to demonstrate high overall response rates in heavily pretreated patients with relapsed or refractory multiple myeloma ...

3. onclive.com onclive.com/view/preliminary-efficacy-safety-data-drive-further-exploration-of-mezigdomide-based-combinations-in-r-r-myeloma

Preliminary Efficacy, Safety Data Drive Further Exploration ... David S. Siegel, MD, PhD, discusses early safety and efficacy data that support further development of mezigdomide-based combinations in multiple myeloma.

4. myeloma.org myeloma.org/videos/mezigdomide-new-drug-combination-trial-results-multiple-myeloma-treatment

Mezigdomide: New Drug Combination Trial Results for ... MEZId combined with TAZ, BMS-986158, or TRAM demonstrated significant efficacy in RRMM. Primary endpoints included defining recommended phase 2 ...

5. ahdbonline.com ahdbonline.com/issues/2024/november-2024-vol-17-payers-guide/ongoing-analyses-and-recent-data-for-talvey-in-multiple-myeloma

Ongoing Analyses and Recent Data for Talvey in Multiple ... MonumenTAL-1 (NCT03399799/NCT04634552) was a phase 1/2 study that had shown a 73% overall response rate (ORR) in 100 patients receiving a 0.4-mg ...

6. myeloma.org myeloma.org/videos/mezigdomide-mezi-plus-dexamethasone-dex-daratumumab-dara-or-elotuzumab-elo-patients-pts

MEZI Combo Therapy for Relapsed Myeloma From the abstract: “MeziDd showed promising efficacy and a manageable safety profile in patients with RRMM and 2 to 4 prior lines of therapy, as ...