A Phase 1b Trial of Teclistamab in Combination With Iberdomide for Relapsed/Refractory Multiple Myeloma

Plain English Summary

Testing Teclistamab (TECVAYLI) in Combination With Iberdomide for Relapsed or Refractory Multiple Myeloma is a Phase 1 clinical trial sponsored by National Cancer Institute (NCI) studying Recurrent Multiple Myeloma, Refractory Multiple Myeloma. This trial is testing a new combination of two drugs, teclistamab and iberdomide, for patients whose multiple myeloma has returned or stopped responding to treatment. It is for adults with multiple myeloma that has relapsed or is refractory, and who have previously received at least four different types of anti-myeloma treatments. Participants will receive iberdomide orally and teclistamab, and will undergo regular blood tests, bone marrow biopsies, and imaging scans. Alternative treatments for relapsed/refractory multiple myeloma include other chemotherapy, targeted therapies, and immunotherapies. The trial aims to enroll 26 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with confirmed multiple myeloma. Patients must have received at least four prior lines of therapy, including specific types of drugs like proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies. Individuals must have measurable disease and meet specific blood count, organ function, and cardiac health requirements. Patients with treated brain metastases are eligible if there's no sign of progression, and those with active brain metastases may be eligible if immediate CNS treatment isn't needed. This trial is studying Recurrent Multiple Myeloma, Refractory Multiple Myeloma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary goal is to determine the safest dose and identify any dose-limiting side effects of combining iberdomide with teclistamab, which will help establish the best way to use this new combinatio The specific primary outcome measures are: Recommended phase 2 dose (RP2D) of iberdomide when combined with teclistamab (At 28 days); Maximum tolerated dose (MTD) of iberdomide when combined with teclistamab (At 28 days). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial aims to find a safer and more effective treatment combination for multiple myeloma patients who have exhausted other options, addressing a significant unmet need in advanced disease. This research targets Recurrent Multiple Myeloma, Refractory Multiple Myeloma, where improved treatment options are needed.

Investor Insight

This trial explores a novel combination therapy for a difficult-to-treat cancer, potentially expanding the treatment landscape for multiple myeloma and representing an investment in next-generation im Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of teclistamab and iberdomide, and how this combination might affect your specific condition. Understand that participation involves regular clinic visits for drug administration, blood draws, bone marrow biopsies, and imaging. Be prepared for potential side effects and discuss any new or worsening symptoms with your healthcare team immediately. This trial is currently recruiting participants. The trial is being conducted at 14 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 26 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo blood and urine sample collection
• PROCEDURE: Bone Marrow Aspiration — Undergo bone marrow aspiration and biopsy
• PROCEDURE: Bone Marrow Biopsy — Undergo bone marrow aspiration and biopsy
• PROCEDURE: Computed Tomography — Undergo PET/CT
• DRUG: Iberdomide — Given PO

Primary Outcomes

• Recommended phase 2 dose (RP2D) of iberdomide when combined with teclistamab (At 28 days)
• Maximum tolerated dose (MTD) of iberdomide when combined with teclistamab (At 28 days)

Secondary Outcomes

• Incidence of adverse events (AEs) (Up to 4 weeks after last dose of study treatment)
• Overall response rate (ORR) (Up to 2 years after last dose of study treatment)
• Minimal residual disease (MRD) negativity (Up to 2 years after last dose of study treatment)
• Progression-free survival (PFS) (From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 2 years after last dose of study treatment)
• Time to progression (From registration to the earliest date of documentation of disease progression, assessed up to 2 years after last dose of study treatment)

Full Eligibility Criteria

Inclusion Criteria:

* Patients must have histologically or cytologically confirmed multiple myeloma (MM), as defined in the International Myeloma Working Group (IMWG) criteria
* If patients have undergone autologous stem cell transplant (SCT), day 0 of SCT must be \> 100 days to be eligible for the study
* Patients must have had disease progression after ≥ 4 prior lines of anti-myeloma treatments including one proteasome inhibitor (e.g., bortezomib, carfilzomib, ixazomib), one immunomodulatory imide drug (ImiD) (e.g., thalidomide, lenalidomide, pomalidomide \[POM\]), and one anti-CD38 monoclonal antibody (e.g., daratumumab, isatuximab)
* Patients must have measurable disease, defined as:

  * Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L)
  * Urine M-protein ≥ 200 mg/24 h
  * Serum free light chain (FLC) assay: "involved" FLC level ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65)
  * Note: Patients with non-secretory disease will be allowed to participate
* Age ≥ 18 years

  * Because no dosing or adverse event data are currently available on the use of iberdomide in combination with teclistamab in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60)
* Hemoglobin ≥ 7.0 g/dL (≤ 28 days prior to registration) (Without growth factor support, blood transfusion, or platelet stimulating agents for the past 7 days, excluding erythropoietin)
* Absolute neutrophil count ≥ 1,000/mcL (≤ 28 days prior to registration) (Without growth factor support, blood transfusion, or platelet stimulating agents for the past 7 days, excluding erythropoietin)
* Platelets ≥ 50,000/mcL (≤ 28 days prior to registration) (Without growth factor support, blood transfusion, or platelet stimulating agents for the past 7 days, excluding erythropoietin)
* Total bilirubin ≤ 2 x institutional upper limit of normal (ULN) (≤ 28 days prior to registration)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN (≤ 28 days prior to registration)
* Estimated glomerular filtration rate (eGFR) \> 30 mL/min (≤ 28 days prior to registration)
* Spot urine (albumin/creatine ratio) ≤ 500mg/g (56 mg/mmol) OR urine dipstick negative/trace (if \> 1+ only eligible if confirmed ≤ 500 mg/g (56 mg/mmol) by albumin/creatinine ratio (spot urine from first void) (≤ 28 days prior to registration)
* Note: Laboratory results obtained during screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the investigator may re-test the subject and the subsequent within range screening result may be used to confirm eligibility
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging done a minimum of 28 days after completion of central nervous system (CNS)-directed therapy shows no evidence of progression
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* Based on the mechanism of action, teclistamab may cause fetal harm when administered to a pregnant woman. Females of child-bearing potential (FCBP): should use effective contraception during treatment with teclistamab and for 5 months after the last dose. FCBP should not breast feed during treatment with teclistamab and for 5 months after the last dose. Should a FCBP become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. The effects of iberdomide on the developing human fetus are unknown. However, IMiDs a

Trial Locations

• Mayo Clinic Hospital in Arizona, Phoenix, Arizona, United States
• Smilow Cancer Hospital-Derby Care Center, Derby, Connecticut, United States
• Smilow Cancer Hospital Care Center - Guilford, Guilford, Connecticut, United States
• Yale University, New Haven, Connecticut, United States
• Yale-New Haven Hospital North Haven Medical Center, North Haven, Connecticut, United States
• Mayo Clinic in Florida, Jacksonville, Florida, United States
• Moffitt Cancer Center, Tampa, Florida, United States
• University of Kansas Cancer Center, Kansas City, Kansas, United States
• University of Kansas Cancer Center-Overland Park, Overland Park, Kansas, United States
• University of Kansas Hospital-Westwood Cancer Center, Westwood, Kansas, United States
• ...and 4 more locations

Frequently Asked Questions

Related Conditions

• Multiple Myeloma
• Recurrent Multiple Myeloma
• Refractory Multiple Myeloma
• Plasma Cell Neoplasm
• Monoclonal Gammopathy
• Amyloidosis
• Waldenstrom Macroglobulinemia
• Lymphoma
• Leukemia
• Bone Marrow Diseases

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