Teclistamab + Iberdomide for Multiple Myeloma

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, CYP3A4/5 modulators

Disqualifiers: Active infections, Plasma cell leukemia, others

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 4 years

26 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial tests the safety, side effects, and best dose of iberdomide in combination with teclistamab in treating multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Iberdomide is a medication that belongs to a group of drugs known as cereblon E3 ligase modulators. Iberdomide works by targeting and destroying proteins that help myeloma cancer cells to survive. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as teclistamab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving iberdomide in combination with teclistamab may be safe and tolerable in treating patients with relapsed or refractory multiple myeloma.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude patients who are taking certain anticancer therapies or medications that strongly affect liver enzymes (CYP3A4/5). It's best to discuss your current medications with the trial team to see if they might interfere with the study.

What data supports the effectiveness of the drug Teclistamab + Iberdomide for Multiple Myeloma?

Teclistamab has been approved for use in patients with relapsed or refractory multiple myeloma, showing a 60% overall response rate in a clinical trial. Additionally, iberdomide is a new immunomodulatory drug that has shown promising results in recent studies. ^{1 2 3 4 5}

What safety data exists for the treatment of Teclistamab and Iberdomide in humans?

Iberdomide, when combined with dexamethasone, has been studied for safety in patients with multiple myeloma, showing some serious side effects like pneumonia, sepsis, and kidney failure. Immunomodulatory drugs similar to Iberdomide have been linked to heart, gastrointestinal, and respiratory issues, and further investigation is needed to confirm these findings. ^{6 7 8 9 10}

How is the drug combination of Teclistamab and Iberdomide unique for treating multiple myeloma?

The combination of Teclistamab and Iberdomide is unique because it combines a bispecific T-cell engager (Teclistamab) that directs the immune system to attack myeloma cells with Iberdomide, a novel drug that enhances immune response and has shown synergy with other treatments. This approach targets multiple pathways in the disease, potentially overcoming resistance to standard therapies. ^{3 6 7 11 12}

Research Team

Ricardo D. Parrondo, M.D.

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

This trial is for adults over 18 with multiple myeloma that's returned or isn't responding to treatment. They must have tried at least four prior treatments, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. If they've had a stem cell transplant, it must be more than 100 days ago.

Inclusion Criteria

My myeloma has worsened after 4 different treatments including a proteasome inhibitor, an ImiD, and an anti-CD38 antibody.

I have been diagnosed with multiple myeloma according to IMWG criteria.

It has been over 100 days since my stem cell transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive teclistamab subcutaneously and iberdomide orally in cycles repeating every 28 days for up to 4 years, with regular monitoring through blood and urine sample collection, bone marrow aspiration and biopsy, and imaging studies.

Up to 4 years

Multiple visits per cycle for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3-6 months.

Up to 2 years

Follow-up visits every 3-6 months

Treatment Details

Interventions

• Iberdomide
• Teclistamab

Trial Overview The trial tests the safety and best dose of Iberdomide combined with Teclistamab in patients with relapsed/refractory multiple myeloma. Iberdomide targets proteins aiding cancer cells; Teclistamab is an immune system-boosting monoclonal antibody.

Participant Groups

Group I: Treatment (iberdomide, teclistamab) Experimental Treatment 8 Interventions

Patients receive teclistamab SC on days 1, 4, 7, 15 and 22 for cycle 1 and days 1, 8, 15 and 22 for remaining cycles. Patients also receive iberdomide PO QD on days 1-21 for cycle 2 and beyond. Cycles repeat every 28 days for up to 4 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood and urine sample collection, bone marrow aspiration and biopsy and CT, PET/CT or MRI throughout the trial.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Teclistamab, a bispecific antibody targeting CD3 and BCMA, has received conditional approval in the EU and full approval in the US for treating adult patients with relapsed or refractory multiple myeloma after multiple prior therapies.

The approvals are based on its efficacy in patients who have undergone at least three to four previous treatments, including specific types of therapies, highlighting its role as a treatment option for difficult-to-treat cases of multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab: First Approval. Kang, C.[2022]

The introduction of new therapies, including proteasome inhibitors, immunomodulators, and various immunotherapies like CAR T-cell treatments, has significantly improved the five-year survival rate for multiple myeloma to nearly 60%.

Despite these advancements, multiple myeloma remains incurable, as patients often become resistant to treatments and experience relapses, highlighting the need for ongoing research and development of new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. Abramson, HN.[2023]

Recent advancements in multiple myeloma treatment, including proteasome inhibitors and immunomodulatory drugs, have significantly improved patient outcomes, but drug resistance remains a challenge.

New therapies such as venetoclax, selinexor, iberdomide, isatuximab, and CAR T-cell therapy show promising results in overcoming resistance and improving treatment efficacy for patients with refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Multiple myeloma: a focus on drugs under development]. Sunami, K.[2020]

Teclistamab-cqyv is an FDA and EMA-approved bispecific antibody that effectively targets multiple myeloma (MM) by engaging T cells to attack cancer cells, showing a 60% overall response rate in heavily pretreated relapsed/refractory patients.

This treatment is specifically designed for patients who have undergone at least three prior therapies and have shown disease progression, highlighting its role in advanced stages of MM where other treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv in multiple myeloma. Martino, EA., Bruzzese, A., Labanca, C., et al.[2023]

Teclistamab, a bispecific antibody targeting B-cell maturation antigen and CD3, has shown promising efficacy in treating relapsed/refractory multiple myeloma, with the recommended Phase II dose established at 1.5 mg/kg subcutaneously, which maintains drug levels above the effective concentration needed for maximum cytotoxicity.

The study utilized pharmacokinetic modeling to predict effective dosing ranges, confirming that doses of 0.27 mg/kg and 0.72 mg/kg intravenously, as well as 0.72 mg/kg subcutaneously, achieved serum concentrations that correlate with effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma. Girgis, S., Lin, SXW., Pillarisetti, K., et al.[2022]

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]

Multiple myeloma remains an incurable disease with increasing incidence, and while current treatments using proteasome inhibitors and immunomodulatory drugs have improved outcomes, many patients still experience relapses and resistance.

Iberdomide, a new drug with high specificity for the Ikaros and Aiolos proteins, represents a promising direction in developing more targeted therapies for multiple myeloma, potentially improving treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review on the treatment of multiple myeloma with small molecular agents in the past five years. Zhang, Z., Liu, X., Zhao, L., et al.[2022]

A comprehensive analysis of adverse event reports for thalidomide, lenalidomide, and pomalidomide revealed significant safety signals, including thalidomide's association with cardiac disorders and lenalidomide's gastrointestinal issues, highlighting the need for careful monitoring in patients.

Pomalidomide was found to have a lower risk of venous thromboembolism compared to thalidomide and lenalidomide, making it a potentially safer option for patients, especially those with renal insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. Jiang, T., Su, H., Li, Y., et al.[2022]

Bortezomib (BOR) demonstrated a higher effectiveness and faster action compared to thalidomide (THAL) in treating refractory multiple myeloma, significantly prolonging survival in patients resistant to THAL.

Common side effects of BOR included thrombocytopenia and leucopenia, but no new adverse events or fatalities were reported, suggesting it is a safe option for first-line treatment and may improve patient prognosis, with serum alkaline phosphatase levels potentially serving as a marker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical assessment of bortezomib for multiple myeloma in comparison with thalidomide. Satoh, M., Oguro, R., Yamanaka, C., et al.[2015]

In a study of 85 newly diagnosed multiple myeloma patients, a high-dose bortezomib regimen (1.6 mg/m2) resulted in a significantly higher complete response rate (43.6%) compared to a low-dose regimen (1.3 mg/m2) which had a response rate of only 12.8%.

While the high-dose regimen showed improved efficacy, particularly in younger patients and those with advanced disease, it was associated with a higher incidence of severe diarrhea, leading to more dose reductions in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients. Li, F., Yao, FS., Zhu, XJ., et al.[2021]

Recent advancements in anti-myeloma treatments, including thalidomide, lenalidomide, and bortezomib, have shown significant clinical responses, especially in patients who do not respond to traditional chemotherapy.

The review highlights the ongoing development of various novel therapeutic classes, such as second-generation proteasome inhibitors and HDAC inhibitors, which are currently in clinical trials or advanced preclinical stages, indicating a promising expansion of treatment options for myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From the bench to the bedside: emerging new treatments in multiple myeloma. Mitsiades, CS., Hayden, PJ., Anderson, KC., et al.[2023]

Multiple myeloma is a challenging disease to treat, especially in elderly patients who may not tolerate aggressive therapies, highlighting the need for safer, more effective treatment options.

New investigational agents like thalidomide, PS-341, and arsenic trioxide show promise due to their unique mechanisms of action, suggesting that combination therapies could enhance efficacy while minimizing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nontraditional cytotoxic therapies for relapsed/refractory multiple myeloma. Hussein, MA.[2019]

References

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

Teclistamab: First Approval. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. [2023]

3. Japan pubmed.ncbi.nlm.nih.gov

[Multiple myeloma: a focus on drugs under development]. [2020]

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

Teclistamab-cqyv in multiple myeloma. [2023]

5. France pubmed.ncbi.nlm.nih.gov

Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma. [2022]

6. 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]

7. France pubmed.ncbi.nlm.nih.gov

A review on the treatment of multiple myeloma with small molecular agents in the past five years. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical assessment of bortezomib for multiple myeloma in comparison with thalidomide. [2015]

10. Germany pubmed.ncbi.nlm.nih.gov

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

From the bench to the bedside: emerging new treatments in multiple myeloma. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Nontraditional cytotoxic therapies for relapsed/refractory multiple myeloma. [2019]