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

Recruiting now · Phase 1

Conditions studied: Recurrent Multiple Myeloma, Refractory Multiple Myeloma

In brief

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.

Key facts

Study ID

NCT06465316

Run by

National Cancer Institute (NCI)

People needed

26

Starts

2024-12-06

Expected to finish

2026-12-31

Last updated by the study team

2026-06-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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)
• 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

You may not qualify if…

• Patients who have active plasma cell leukemia, active amyloid light chain (AL) (primary) amyloidosis, active 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 SCT. Autologous SCT is allowed
• Patients who received a live or live-attenuated vaccine ≤ 30 days prior to registration. Patients are allowed to receive a coronavirus disease 2019 (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)
• Patients who require immunosuppressive medications including, but not limited to, systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent. Use of immunosuppressive medications for the management of iberdomide-related adverse events (AEs) or in subjects with contrast allergies is acceptable. In addition, use of inhaled, topical, intranasal corticosteroids or local steroid injection (e.g., intra-articular injection) is permitted. Temporary use of corticosteroids for concurrent illnesses (e.g., food allergies, computed tomography [CT] scan contrast hypersensitivity, pneumonia, etc.) are acceptable
• Patients who require medications that are strong inhibitors or inducers of CYP3A4/5
• Patients who are receiving any other investigational agents
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
• Pregnant women are excluded from this study because iberdomide is a thalidomide analog and thalidomide is a known human teratogen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with iberdomide, breastfeeding should be discontinued if the mother is treated with iberdomide. These potential risks may also apply to other agents used in this study
• Patients who are unable or unwilling to undergo protocol required thromboembolism prophylaxis are excluded

Where it is running

• VCU Massey Comprehensive Cancer Center — Richmond, Virginia, United States (enrolling)
• Smilow Cancer Hospital-Derby Care Center — Derby, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center - Guilford — Guilford, Connecticut, United States (enrolling)
• Yale University — New Haven, Connecticut, United States (enrolling)
• Yale-New Haven Hospital North Haven Medical Center — North Haven, Connecticut, United States (enrolling)
• Mayo Clinic in Florida — Jacksonville, Florida, United States (enrolling)
• Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States (enrolling)
• University of Kansas Cancer Center — Kansas City, Kansas, United States (enrolling)
• University of Kansas Cancer Center-Overland Park — Overland Park, Kansas, United States (enrolling)
• University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States (enrolling)
• Mayo Clinic in Rochester — Rochester, Minnesota, United States (enrolling)
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (enrolling)
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States (enrolling)
• Moffitt Cancer Center — Tampa, Florida, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.