Talquetamab + Iberdomide + Dexamethasone for Multiple Myeloma

Overseen By UCSF Hematopoietic Malignancies Clinical Trial Recruitment

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Thomas Martin, MD

Must not be taking: Cytotoxic, Biologic, Targeted, others

Disqualifiers: Peripheral neuropathy, Infections, Cardiovascular, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments to help people with multiple myeloma, a type of blood cancer that has either returned after treatment or not responded to previous treatments. The study examines the safety of these drugs, potential side effects, and the optimal dose. The trial involves three drugs: talquetamab, which aids T-cells in killing cancer cells; iberdomide, an experimental drug that targets and destroys proteins that help cancer cells survive; and dexamethasone, which reduces inflammation and is often used in cancer treatment. People with multiple myeloma who have tried other treatments without success might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that certain treatments should not have been received within specific time frames before starting the trial, such as cytotoxic treatments within 3 weeks and biologic treatments within 2 weeks. It's best to discuss your current medications with the trial team to get specific guidance.

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

Previous studies have shown that talquetamab helps the body's T-cells attack and kill myeloma cancer cells. The FDA has approved talquetamab for patients who have tried several other treatments, indicating it is reasonably safe.

Iberdomide remains under study. It works by breaking down proteins that help cancer cells survive. Although still under investigation, no major safety concerns have been widely reported.

Dexamethasone, a well-known drug, reduces swelling and is often used in cancer treatments. It has a long history of use and is generally considered safe when used as directed.

This trial is in an early phase, focusing on the safety of these drugs when used together. Researchers are closely monitoring for any side effects. While talquetamab and dexamethasone have established safety records, iberdomide's safety is still under close examination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Talquetamab combined with Iberdomide and Dexamethasone for multiple myeloma because it offers a novel approach compared to standard treatments like proteasome inhibitors and immunomodulatory drugs. Talquetamab is unique because it targets a specific protein on myeloma cells called GPRC5D, which is different from typical targets like CD38 or BCMA. This targeted approach could lead to more precise destruction of cancer cells with potentially fewer side effects. Additionally, Iberdomide is an emerging drug with a new mechanism, designed to boost the immune response against cancer cells, offering a fresh angle in the fight against multiple myeloma.

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

Research shows that talquetamab can help fight multiple myeloma by guiding T-cells (a type of immune cell) to attack cancer cells. In this trial, participants will receive talquetamab with iberdomide and dexamethasone. Iberdomide targets proteins that myeloma cells need to survive, aiding in their destruction. While the FDA has approved talquetamab, iberdomide is still under evaluation for effectiveness. Dexamethasone, a steroid, reduces inflammation and is commonly used to treat multiple myeloma. Together, these drugs aim to combat myeloma in different ways, offering hope for patients whose cancer has returned or resisted other treatments. ^{1 2 5 6 7}

Who Is on the Research Team?

Thomas Martin, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for patients with multiple myeloma that has returned (relapsed) or hasn't improved with treatment (refractory). Participants should have previously tried and not responded well to certain other treatments, including BCMA targeted therapy.

Inclusion Criteria

Must have at least 2 negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test result obtained prior to initiating therapy if female

I agree to use birth control methods if I can have children.

My blood counts are within a healthy range.

Exclusion Criteria

I have a serious heart condition.

I have had previous treatments targeting GPRC5D or received Iber.

I still have major side effects from past cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive Talquetamab, Iberdomide, and Dexamethasone in escalating doses to determine the maximum tolerated dose

Up to 1 cycle (28 days)

Visits every 2 weeks

Dose Expansion

Participants receive the recommended phase 2 dose of the drug combination to further assess safety and efficacy

28-day cycles, repeated as long as there is clinical benefit

Visits every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 8 weeks for up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bone Marrow Biopsy
• Dexamethasone
• Talquetamab

Trial Overview The trial tests a combination of talquetamab, iberdomide, and dexamethasone for safety and effectiveness. Talquetamab is FDA-approved alone but is being studied here with the investigational drug iberdomide and the corticosteroid dexamethasone.

How Is the Trial Designed?

Group I: Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone) Experimental Treatment 4 Interventions

Participants receive the recommended phase 2 dose of Iberdomide in combination with Talquetamab and 20-40mg of Dexamethasone which may be continued at the discretion of the investigator. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo bone marrow biopsy, imaging scans, tissue and blood sample collection throughout the study.

Group II: Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone) - Starting Dose Experimental Treatment 4 Interventions

Participants receive 0.8 mg/kg Talquetamab (Tal) subcutaneously (SQ) over 1-3 minutes every 2 weeks (days 1 and 15 of each cycle), 0.75 mg Iberdomide orally (PO) once a day (QD) on days 1-21 of each 28-day cycle, and 20-40mg of Dexamethasone PO weekly, but may be continued at the discretion of the investigator. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo bone marrow biopsy, skeletal x-ray, CT, Positron Emission Tomography (PET)/CT, or MRI, tissue and blood sample collection throughout the study.

Group III: Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone) Experimental Treatment 4 Interventions

Participants receive 0.8 mg/kg Talquetamab (Tal) subcutaneously (SQ) over 1-3 minutes every 2 weeks (days 1 and 15 of each cycle), 1.0 mg Iberdomide orally (PO) once a day (QD) on days 1-21 of each 28-day cycle, and 20-40mg of Dexamethasone PO weekly, but may be continued at the discretion of the investigator. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo bone marrow biopsy, skeletal x-ray, CT, Positron Emission Tomography (PET)/CT, or MRI, tissue and blood sample collection throughout the study.

Talquetamab is already approved in United States, European Union for the following indications:

Approved in United States as Talquetamab for:

• Relapsed or refractory multiple myeloma

Approved in European Union as Talquetamab for:

• Relapsed or refractory multiple myeloma

Who Is Running the Clinical Trial?

Thomas Martin, MD

Lead Sponsor

Trials

4

Recruited

130+

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

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

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

Published Research Related to This Trial

Talquetamab, a bispecific T-cell engager targeting GPRC5D and CD3, has received accelerated approval in the USA and conditional marketing authorization in the EU for treating adults with relapsed or refractory multiple myeloma, highlighting its potential as a new treatment option.

This approval marks a significant milestone in the development of talquetamab, indicating its efficacy and safety in addressing a challenging form of cancer that has not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talquetamab: First Approval. Keam, SJ.[2023]

Talquetamab, a bispecific antibody targeting GPRC5D and CD3, shows similar efficacy and durability of response in treating relapsed or refractory multiple myeloma compared to teclistamab, the first bispecific antibody approved for this condition.

While talquetamab has a lower incidence of infections than teclistamab, it presents unique side effects related to skin, oral, and nails, yet remains a well-tolerated and effective treatment option for patients with heavily pretreated multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. Liu, L., Krishnan, A.[2023]

In two cases of multiple myeloma resistant to conventional therapies, patients showed significant improvement after treatment with bortezomib and dexamethasone, with one patient experiencing a decrease in serum IgG from 8040 to 1020 mg/dl and another from 2140 to 623 mg/dl.

The combination therapy not only proved effective in reducing tumor markers but also resulted in milder adverse reactions when dexamethasone was added, suggesting it may help mitigate side effects associated with bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effective combination therapy of bortezomib and dexamethasone for two patients with refractory multiple myeloma]. Ikeda, H., Hayashi, T., Nojima, M., et al.[2015]

In the MonumenTAL-1 trial, nearly 75% of the 288 patients with relapsed/refractory multiple myeloma showed significant anticancer effects from the investigational drug talquetamab.

Talquetamab is a first-in-class bispecific antibody that targets GPRC5D on malignant plasma cells while sparing normal cells, effectively activating T cells to mount an immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MonumenTAL Results for Talquetamab in Myeloma. [2023]

In the phase 1 MonumenTAL-1 study involving patients with refractory or relapsed multiple myeloma, two doses of talquetamab (405 μg/kg weekly and 800 μg/kg every other week) were found to be well tolerated, with most side effects being mild or moderate, including cytokine release syndrome (CRS).

The treatment showed promising efficacy, with most participants experiencing a reduction in cancer signs and a median duration of response of 8-10 months, indicating talquetamab's potential as a new option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plain language summary of the MonumenTAL-1 study of talquetamab in people with relapsed or refractory multiple myeloma. Chari, A., Askari, E., Caers, J., et al.[2023]

Three new bispecific antibodies—teclistamab, elranatamab, and talquetamab—have received accelerated FDA approval for treating relapsed/refractory multiple myeloma, indicating their potential efficacy in this challenging condition.

While these agents show promise, the medical community is currently awaiting results from randomized phase III clinical trials to better understand their effectiveness compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma. Firestone, R., Lesokhin, AM., Usmani, SZ.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06348108

Study Details | NCT06348108 | Talquetamab in ... Talquetamab is an FDA approved drug that can bring T-cells to the myeloma cell, resulting in myeloma cell death. Iberdomide is an investigational drug and works ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01992

Talquetamab in Combination with Iberdomide and ... Talquetamab can bring T-cells to the myeloma cell, resulting in myeloma cell death. Iberdomide is an investigational drug. Iberdomide works by targeting and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11974566/

Perspectives on Talquetamab and its Utility in the ... In this review, we will discuss the preclinical and clinical development of talquetamab, results from clinical trials both as a single-agent and ...

4. ahdbonline.com ahdbonline.com/articles/ongoing-analyses-and-recent-data-for-talvey-in-multiple-myeloma

Ongoing Analyses and Recent Data for Talvey in Multiple ... Janssen Biotech is currently conducting multiple trials evaluating talquetamab-tgvs in both its current indication and additional lines of therapy.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS7565

Prophylactic interventions for oral toxicities with the ... Background: Talquetamab (Tal) is the first GPRC5D×CD3 bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma ...

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

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ... Talquetamab, recently approved by the FDA and EMA, is indicated for patients who have progressed after at least three or four prior lines of therapy (LOTs).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06348108?term=AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(relapsed%20refractory%20multiple%20myeloma)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING))&rank=10

Talquetamab in Combination With Iberdomide and ... A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...