Iberdomide + Daratumumab + Carfilzomib + Dexamethasone for Multiple Myeloma

(Iber-KDd Trial)

Overseen By Michelle D Armogan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Benjamin T Diamond, MD

Must be taking: Thromboprophylactic agents

Disqualifiers: Plasma cell leukemia, COPD, Amyloidosis, Uncontrolled hypertension, Active hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new combination of medications to help people with multiple myeloma, a type of blood cancer, when other treatments have stopped working. Researchers aim to determine if this combination can prevent the cancer from returning or growing. The trial will assess the effectiveness of these drugs together and their tolerability for patients. Individuals diagnosed with multiple myeloma, whose condition has worsened despite previous treatments, might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires a 2-week period without prior multiple myeloma treatments before starting the study medications. However, some medications like corticosteroids for non-myeloma conditions and bone-targeting agents are allowed. 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?

Studies have shown that the combination of iberdomide, carfilzomib, daratumumab, and dexamethasone is generally well-tolerated in patients with multiple myeloma. Research indicates that this combination, often called Iber-KDd, was safe for patients who had already received many treatments. Its safety profile aligns with findings from earlier studies involving similar drugs.

Iberdomide, when used alone, has also demonstrated general safety. It showed promising results even in patients who had undergone many previous treatments. Overall, the available data suggest that these treatments are well-tolerated, with no major safety concerns reported so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they combine several innovative therapies that work together to tackle the disease more effectively. Unlike traditional treatments that might focus on a single pathway or mechanism, this combination uses Iberdomide, which modulates the immune system to enhance anti-cancer responses, alongside Carfilzomib and Daratumumab, which target and destroy cancer cells directly. Additionally, the use of Dexamethasone helps reduce inflammation and enhances the efficacy of the other drugs. This multi-faceted approach aims to improve treatment outcomes and provide a more comprehensive attack on multiple myeloma, offering hope for better patient responses compared to existing options.

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

Studies have shown that using the drugs carfilzomib, daratumumab, and dexamethasone together effectively treats multiple myeloma, a type of blood cancer. In this trial, participants will receive a combination of these drugs with iberdomide, known as Iber-KDd therapy, which has shown promising results for patients who haven't had success with other treatments. Patients using similar drug combinations have experienced significant reductions in their cancer. Additionally, research on iberdomide alone has demonstrated that it can help patients live longer. These findings suggest that Iber-KDd therapy could be a strong option for managing multiple myeloma. ^{1 2 3 4 6}

Who Is on the Research Team?

Carl Landgren, MD

Principal Investigator

University of Miami

Benjamin Diamond, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for adults under 75 with relapsed/refractory multiple myeloma who've had 1-3 prior treatments, including a lenalidomide regimen. They must have adequate blood counts, liver function, and kidney clearance. Those with certain heart or lung conditions, active infections like HIV or hepatitis B/C, significant neuropathy, or are pregnant can't join.

Inclusion Criteria

I am using birth control and have had a recent negative pregnancy test.

My liver tests are within normal limits.

I have multiple myeloma that got worse after or during my last treatment, and I've had 1-3 prior treatments including one with lenalidomide.

Exclusion Criteria

Pregnant or lactating females

You have HIV, hepatitis B, or hepatitis C.

I have not had major surgery in the last 3 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Iber-KDd Combination Therapy

Participants receive up to eight 28-day cycles of Iberdomide, Carfilzomib, Daratumumab, and Dexamethasone therapy

8 months

Iber Monotherapy

Participants receive up to twelve 28-day cycles of Iberdomide monotherapy in the absence of disease progression

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Daratumumab
• Dexamethasone
• Iberdomide

Trial Overview

The study tests a new combination therapy called Iber-KDd (iberdomide with carfilzomib, daratumumab & dexamethasone) against standard treatments for multiple myeloma to see if it's more effective and tolerable in shrinking the cancer or preventing its return.

How Is the Trial Designed?

Group I: Iber-KDd Combination Therapy Experimental Treatment 7 Interventions

Prior to Iber-KDd combination therapy, participants will receive Acetaminophen, Diphenhydramine and Montelukast therapy per protocol. Participants will receive up to eight (8) 28-day cycles of combination Iberdomide (I), Carfilzomib (K), Daratumumab (D), and Dexamethasone (d) (Iber-KDd) therapy. Participants will receive Iber-KDd combination therapy for approximately 8 months. In the absence of disease progression, participants will continue on to Iber monotherapy. Participants with disease progression will discontinue study therapy but will continue to be followed for up to three (3) years after conclusion of Iber-KDd combination therapy.

Group II: Iber Monotherapy Experimental Treatment 1 Intervention

After completion of Iber-KDd combination therapy, and In the absence of disease progression, participants will then receive up to twelve (12) 28-day cycles of Iberdomide (Iber) monotherapy. Participants will receive Iber monotherapy for up to 12 months or until disease progression. Participants will be followed for up to three (3) years after conclusion of Iber monotherapy. Total study participation is up to five (5) years.

Carfilzomib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Benjamin T Diamond, MD

Lead Sponsor

Trials

1

Recruited

30+

Carl Ola Landgren, MD, PhD

Lead Sponsor

Trials

2

Recruited

80+

Bristol-Myers Squibb

Industry 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

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 phase 3 study involving 466 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib, dexamethasone, and daratumumab (KdD) significantly improved progression-free survival compared to carfilzomib and dexamethasone alone (Kd), with a hazard ratio of 0.63, indicating a 37% reduction in the risk of disease progression.

Despite a higher incidence of grade 3 or higher adverse events in the KdD group (82%) compared to the Kd group (74%), the overall safety profile was considered favorable, with similar rates of treatment discontinuation due to adverse events in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Dimopoulos, M., Quach, H., Mateos, MV., et al.[2020]

In a phase 3 study (CASTOR) with a median follow-up of 19.4 months, the combination of daratumumab, bortezomib, and dexamethasone significantly improved progression-free survival (16.7 months) compared to bortezomib and dexamethasone alone (7.1 months), indicating its efficacy in treating relapsed/refractory multiple myeloma.

Daratumumab plus bortezomib and dexamethasone also showed a higher overall response rate (83.8% vs. 63.2%) and was particularly beneficial for patients with one prior line of therapy, demonstrating a favorable safety profile consistent over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Spencer, A., Lentzsch, S., Weisel, K., et al.[2019]

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 3 CANDOR study involving 466 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib, daratumumab, and dexamethasone (KdD) demonstrated a significantly longer median progression-free survival of 28.6 months compared to 15.2 months for carfilzomib and dexamethasone (Kd), indicating KdD's potential as a new standard-of-care treatment.

While KdD showed improved efficacy, it was associated with a higher incidence of grade 3 or worse treatment-emergent adverse events (87% in KdD vs. 76% in Kd), including thrombocytopenia and pneumonia, highlighting the need for careful monitoring of patients receiving this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Usmani, SZ., Quach, H., Mateos, MV., et al.[2022]

The combination therapy of daratumumab, carfilzomib, lenalidomide, and dexamethasone (D-KRd) was well tolerated in a study of 22 patients with newly diagnosed multiple myeloma, with a high overall response rate of 95%.

Most treatment-emergent adverse events were mild, with the most common being diarrhea and lymphopenia, and infusion-related reactions were primarily mild, indicating a favorable safety profile for D-KRd therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab Plus Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma. Jakubowiak, A., Usmani, SZ., Krishnan, A., et al.[2022]

In a study involving 792 patients with relapsed multiple myeloma, the combination of carfilzomib with lenalidomide and dexamethasone significantly improved progression-free survival, with a median of 26.3 months compared to 17.6 months for the control group.

The carfilzomib group also showed a higher overall response rate (87.1% vs. 66.7%) and better health-related quality of life, indicating a favorable risk-benefit profile despite similar rates of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. Stewart, AK., Rajkumar, SV., Dimopoulos, MA., et al.[2022]

Citations

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This study will examine the tolerability and efficacy of this combination therapy for all participants and the ability of this combination therapy to shrink or ...

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Induction therapy with KID appears safe and effective leading to deep responses and adequate stem cell collection despite short tx duration.

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Iberdomide, Daratumumab, Carfilzomib, and ...

This phase II trial tests how well iberdomide, daratumumab, carfilzomib and dexamethasone work in treating patients with multiple myeloma.

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In pts with heavily pretreated RRMM, IberDd, IberVd, and IberKd showed a tolerable safety profile and promising efficacy.

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myeloma.org/treatment/multiple-myeloma-medications/iberdomide

Iberdomide

Induction therapy with proteasome inhibitor Kyprolis® (carfilzomib), iberdomide, and the steroid dexamethasone [KID] appears safe and did not interfere with ...