Talquetamab + Iberdomide + Dexamethasone for Multiple Myeloma

Overseen By Essence Fisher-Hobson

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

Trial Summary

What is the purpose of this trial?

This phase I trial will evaluate the safety, side effects, and best dose of talquetamab in combination with iberdomide and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). There is currently a significant unmet need for patients with relapsed or refractory multiple myeloma (RRMM) who are triple class refractory and have been exposed to B-cell maturation antibody (BCMA) targeted therapy. These patients currently have limited treatment options and poor survival. 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 by targeting and destroying proteins that help myeloma cancer cells to survive. Dexamethasone is a corticosteroid, is similar to a natural hormone produced by the adrenal glands to reduce inflammation (swelling, heat, redness, and pain) and is used to in helping to treat certain types of cancer including myeloma.

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.

What data supports the effectiveness of the drug Talquetamab for treating multiple myeloma?

Talquetamab has shown promising results in treating multiple myeloma, with nearly 75% of patients in a clinical trial experiencing significant anticancer effects. It works by targeting specific proteins on cancer cells and activating the body's immune response to fight the cancer. ^{1 2 3 4 5}

Is the combination of Talquetamab, Iberdomide, and Dexamethasone safe for humans?

Talquetamab has been shown to be generally well-tolerated in humans, with some unique side effects like skin, oral, and nail issues, but fewer infections compared to similar treatments. It has been approved for use in relapsed or refractory multiple myeloma, indicating a level of safety in this context. ^{1 2 3 5 6}

What makes the drug Talquetamab unique for treating multiple myeloma?

Talquetamab is unique because it is a first-in-class bispecific antibody that targets a specific protein (GPRC5D) found on cancerous plasma cells, while also engaging T-cells to activate an immune response, offering a novel approach compared to traditional treatments. ^{1 2 6 7 8}

Research Team

Thomas Martin, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

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

Findings from Research

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]

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]

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]

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]

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]

References

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

Talquetamab: First Approval. [2023]

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

MonumenTAL Results for Talquetamab in Myeloma. [2023]

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

An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma. [2023]

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

Thalidomide in patients with advanced multiple myeloma: a study of 83 patients--report of the Intergroupe Francophone du Myélome (IFM). [2016]

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

Plain language summary of the MonumenTAL-1 study of talquetamab in people with relapsed or refractory multiple myeloma. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

[Effective combination therapy of bortezomib and dexamethasone for two patients with refractory multiple myeloma]. [2015]

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

Thalidomide in the management of multiple myeloma. [2019]