This phase I/II study is trying to understand how safe and effective a new targeted therapy (CC-92480) is when administered alone, or in combination with steroids (dexamethasone) in people with relapsed or refractory multiple myelomaA Phase 1/2 Multicenter, Open-label Study to Assess the Safety, Pharmacokinetics and Efficacy of CC-92480 Monotherapy and in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma

Exclusion

1. Subject has a significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Subject has any condition that confounds the ability to interpret data from the study.
4. Subject has non-secretory multiple myeloma.
5. Subject has refractory primary multiple myeloma (ie, no history of at least a minor response to a prior treatment regimen).
6. Subject has plasma cell leukemia or active leptomeningeal myelomatosis.
7. Subject has documented, systemic light chain amyloidosis or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS) Syndrome.
8. Subject has immunoglobulin class M (IgM) myeloma.
9. Part 1: Subject has a history of allogeneic bone marrow transplantation. Part 2: Subject has a history of allogeneic bone marrow transplantation within 6 months prior to first dose. Subject should not have ongoing graft-versus-host disease (GVHD) requiring systemic immunosuppression.
10. Subject is undergoing dialysis.
11. Subjects with peripheral neuropathy ≥ Grade 2.
12. Subjects with gastrointestinal disease that may significantly alter the absorption of CC-92480.

13. Subject has impaired cardiac function or clinically significant cardiac disease, including any of the following:

    • LVEF < 45% as determined by ECHO or MUGA scan at Screening.
    • Complete left bundle branch, bifascicular block or other clinically significant abnormal electrocardiographic (ECG) finding at Screening.
    • A prolongation of QT interval on Screening ECG as defined by repeated demonstration of a QTc interval >480 milliseconds (ms) using Fridericia's QT correction formula; a history of or current risk factors for Torsades de Pointe (eg, heart failure, hypokalemia, or a family history of Long QT Syndrome); and concurrent administration of medications that prolong the QT/QTc interval.
    • Congestive heart failure (New York Heart Association Class III or IV).
    • Myocardial infarction ≤6 months prior to starting CC-92480.
    • Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris.
14. Concurrent administration of strong CYP3A modulators; concurrent administration of proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole) ≤ 2 weeks prior to starting CC-92480.
15. Subject had prior systemic myeloma treatment with an investigational anti-myeloma agent (eg, anti-PD-1, anti-PD-L1) ≤ 5 half-lives prior to starting CC-92480 (not applicable for subjects who had CAR-T as last prior regimen); subject had prior exposure to approved myeloma therapies (including therapeutic monoclonal antibodies such as anti-CD38 or anti-SLAMF7) ≤ 5 half-lives or within 4 weeks prior to starting CC-92480 whichever is shorter.
16. Subject had major surgery ≤ 2 weeks prior to starting CC-92480. Note: Subjects must have recovered from any clinically significant effects of recent surgery.
17. Subject is a pregnant or nursing female, or intends to become pregnant or donate ova during participation in the study.
18. Subject has known human immunodeficiency virus (HIV) infection.
19. Subject has known active chronic hepatitis B or C virus (HBV/HCV) infection.
20. Subject has a history of concurrent second cancer requiring ongoing systemic treatment.

21. Subjects has a history of prior malignancy other than MM, except if the subject has been free of disease for ≥3 years OR the subject had one of the following noninvasive malignancies treated with curative intent without known recurrence:

    • Basal or squamous cell carcinoma of the skin.
    • Carcinoma in situ of the cervix or breast.
    • Stage 1 bladder cancer.
    • Incidental histological findings of localized prostate cancer such as tumor stage 1a or 1b (T1a or T1b) using the Tumor/Node/Metastasis (TNM) classification of malignant tumors OR prostate cancer that has been treated with curative intent.
22. Subject has a history of anaphylaxis to thalidomide, lenalidomide, pomalidomide or dexamethasone.
23. Subject has known or suspected hypersensitivity to the excipients (excipients include silica dimethyl silylate, anhydrous colloidal silicon dioxide, mannitol, fumaric acid and stearic acid) contained in the formulation of CC-92480 or dexamethasone.

24. Subject has undergone either of the following within 14 days of initiating CC-92480:

    • Plasmapheresis.
    • Radiation therapy other than local therapy for symptomatic relief of MM associated bone lesions.

25. Subject has received immunosuppressive medication within 14 days prior to the first dose of CC-92480. The following are exceptions to this criterion:

    • Intranasal, inhaled, topical or local corticosteroid injections (eg, intra-articular injection).
    • Systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or the equivalent.
    • Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication).
26. Subject is unable or unwilling to undergo protocol required venous thromboembolism (VTE) prophylaxis.