Testing Teclistamab (TECVAYLI) in Combination With Iberdomide for Relapsed or Refractory Multiple Myeloma

NCT06465316 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2024-0475410620UM1CA186709
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 14

Brief 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.

Conditions

Recurrent Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose (RP2D) of iberdomide when combined with teclistamab

  The RP2D will be defined as the pharmacologically optimal dose of iberdomide that can be combined with teclistamab and will be selected based on all available pharmacokinetic, pharmacodynamic, target engagement, efficacy, safety and tolerability data.

  At 28 days

• Maximum tolerated dose (MTD) of iberdomide when combined with teclistamab

  The MTD will be is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 8 new patients).

  At 28 days

Secondary Outcomes (7)

• 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

Other Outcomes (2)

• Tumor immune microenvironment

  Up to 2 years after last dose of study treatment

• Soluble B-cell maturation antigen levels

  At baseline

Study Arms (1)

Treatment (iberdomide, teclistamab)

EXPERIMENTAL

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 PET/CT or PET/MR throughout the trial.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Iberdomide; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Teclistamab

Interventions

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (iberdomide, teclistamab)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (iberdomide, teclistamab)

Iberdomide DRUG

Given PO

Also known as: CC 220, CC-220

Treatment (iberdomide, teclistamab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT or PET/MR

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (iberdomide, teclistamab)

Teclistamab DRUG

Given SC

Also known as: JNJ 64007957, JNJ-64007957, JNJ64007957, Teclistamab-cqyv, Tecvayli

Treatment (iberdomide, teclistamab)

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (iberdomide, teclistamab)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (iberdomide, teclistamab)

Magnetic Resonance Imaging PROCEDURE

Undergo PET/MR

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (iberdomide, teclistamab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Patients who have active plasma cell leukemia, active amyloid light chain (AL) (primary) amyloidosis, active polyneurophathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, myeloma protein, and skin changes), and Waldenstrom macroglobulinemia are ineligible
• If a patient develops recurrent/refractory (R/R) disease while receiving the most recent line of therapy, there is no need for a washout period
• Patients who have had prior anti-BCMA directed bispecific antibody (BsAb) therapy exposure (prior treatment with anti-BCMA directed antibody drug conjugate, anti-BCMA-directed chimeric antigen receptor (CAR) T cell therapy, and prior non-BCMA-targeting BsAb are permitted)
• Patients who have had prior treatment with a cereblon E3 ligase modulator, including mezigdomide, iberdomide, and CFT7455 (all currently in clinical development)
• Patients who received plasmapheresis ≤ 7 days prior to registration
• Patients who received a prior allogeneic stem cell transplant. Autologous SCT is allowed
• Patients who received a live or live-attenuated vaccine ≤ 30 days prior to registration. Patients are allowed to receive a COVID-19 vaccine at any timepoint during protocol treatment
• Systemic active infection requiring treatment
• Any unresolved toxicity ≥ grade 2 from previous treatment except for alopecia or peripheral neuropathy up to grade 2
• Patients who have had any major surgery ≤ 4 weeks prior to registration
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous
• Patients with evidence of active mucosal or internal bleeding
• Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria
• Patients with known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to teclistamab or iberdomide, or any of the components of the study treatment
• Patients who are taking any anticancer therapy other than hormonal therapy (for prostrate or breast cancer) and palliative radiotherapy (defined as radiation to ≤ 3 sites of active multiple myeloma)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (14)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, 06418, United States

RECRUITING

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, 06437, United States

RECRUITING

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, 06473, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

SUSPENDED

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210, United States

RECRUITING

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Specimen Handling; Biopsy; iberdomide; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Ricardo D Parrondo

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: June 18, 2024
• Study Start: December 6, 2024
• Primary Completion (Estimated): September 16, 2026
• Study Completion (Estimated): September 16, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (14)