Clinical Trial 23563

• Overview

  Study Title:

  A Phase 1b trial of Teclistamab in Combination with Iberdomide for Relapsed/Refractory Multiple Myeloma

  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.

  Objective:

  Primary Objectives: Estimate the RP2D of iberdomide in combination with teclistamab. Secondary Objectives: To evaluate the safety and toxicity profile of iberdomide in combination with teclistamab. To observe and record antitumor activity. Although the clinical benefit of these drugs has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability.

• Treatments

  Therapies:

  Immunomodulators; Immunotherapy

  Medications:

  Iberdomide (); Teclistamab ()

• Inclusion Criteria

  Inclusion Criteria:
  • 18 years of age or older
  • Patients must have histologically or cytologically confirmed multiple myeloma (MM), as defined in the International Myeloma Working Group (IMWG) criteria
  • If patients have undergone 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 as defined in protocol.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60)
  • Lab values as indicated in protocol.
  • 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.
  • Men must agree to abstain from donating and semen or sperm while taking iberdomide, during dose interruptions, and for at least 28 days after the last dose of iberdomide. FCBP must agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period
  • All patients must agree to abstain from donating blood products while taking iberdomide and for at least 28 days after the last dose of iberdomide
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study subjects
  • Willingness to adhere to the study visit schedule and other protocol requirements and provide mandatory blood and bone marrow specimens for correlative research
  • Willingness to return to the enrolling institution for follow-up
  • Additional criteria may apply

• Exclusion Criteria

  Exclusion Criteria:
  • 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 develop R/R disease while not on treatment must have received an investigational drug or approved systemic anti-myeloma therapy (including systemic steroids) ≤ 14 days or 5 half-lives (whichever is shorter) prior to registration. This includes prior treatment with a monoclonal antibody ≤ 30 days before receiving the first dose of a study drug. The only exception is emergency use of a short course of systemic corticosteroids (equivalent to, or less than: dexamethasone 40 mg/day for a maximum of 4 days) before treatment
  • Patients who have had prior anti-BCMA directed BsAb therapy exposure (prior treatment with anti-BCMA directed antibody drug conjugate, or anti-BCMA-directed CAR T cell therapy 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 stem cell transplantation (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 at or within 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
  • Additional criteria apply

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