A 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 CC-92480

What's the purpose of this trial?

This is an open-label, multi-center, international, Phase 1/2 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 (RRMM).

Relapsed and refractory multiple myeloma patients previously treated with at least 3 prior regimens including lenalidomide or pomalidomide, a proteasome inhibitor and a CD38 antibody will be eligible.

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
  2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
  4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
  5. Subjects must have a documented diagnosis of MM and measurable disease at enrollment. Measurable disease is defined as:
    • M-protein quantities ≥ 0.5 g/dL by sPEP or
    • ≥ 200 mg/24 hour urine collection by uPEP or
    • Serum FLC levels > 100 mg/L (milligrams/liter) involved light chain and an abnormal kappa/lambda (κ/λ) ratio in subjects without measurable serum or urine M-protein or
    • For subjects with immunoglobulin class A (IgA), myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥ 0.50 g/dL.
  6. All subjects must have:
    • Received at least 3 prior anti-myeloma regimens including at least 2 consecutive cycles of lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid and a CD38 antibody (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen).
    • Documented disease progression on or within 60 days from the last dose of their last myeloma therapy
      • Subjects who had CAR-T therapy as their last myeloma therapy are eligible as long as they have documented disease progression following CAR-T therapy.
    • In addition to criteria above (a and b), subjects enrolled in Part 2 must have disease refractory to an immunomodulatory agent (lenalidomide and/or pomalidomide), a glucocorticoid, a proteasome inhibitor, and a CD38 antibody. Refractory is defined as disease that is nonresponsive on therapy (failure to achieve minimal response or development of progressive disease), or progresses within 60 days of last dose.
  7. Subjects must have the following laboratory values:
    • Absolute neutrophil count (ANC) ≥ 1.25 x 109/L without growth factor support for ≥ 7 days (≥ 14 days for pegfilgrastim). ANC of ≥ 1.00 x 109/L is permitted for the dose expansion cohorts (Part 2).
    • Hemoglobin (Hgb) ≥ 8 g/dL.
    • Platelets (plt) ≥ 75 x 109/L without transfusion for ≥ 7 days.
    • Corrected serum calcium ≤ 13.5 mg/dL (≤ 3.4 mmol/L).
    • Creatinine clearance (CrCl) based on Cockcroft-Gault formula ≥ 45 mL/min.
    • AST/SGOT and ALT/SGPT ≤ 3.0 x upper limit of normal (ULN).
    • Serum bilirubin ≤ 1.5 x ULN or < 3.0 mg/dL for subjects with documented Gilbert's syndrome.
    • Uric acid ≤ 7.5 mg/dL (446 µmol/L).
    • PT/INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN, (for subjects not receiving therapeutic anticoagulation).
  8. Females of childbearing potential (FCBP) must:
    • Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after discontinuation of CC-92480. This applies even if the subject practices true abstinence* from heterosexual contact.
    • Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, two reliable forms of contraception as defined in the PPP and provided to the subject at the time of informed consent, without interruption, 28 days prior to starting CC-92480, during the study therapy (including during dose interruptions), and for 28 days after discontinuation of study therapy.

Note: A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point and, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).

  1. Male subjects must:

    Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use of a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study (even during dose interruptions) and for at least 3 months following CC-92480 discontinuation in accordance with the PPP provided to the subject at the time of informed consent, even if he has undergone a successful vasectomy.

    * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and coitus interruptus (withdrawal) are not acceptable methods of contraception.

  2. Males must agree to refrain from donating sperm while on CC-92480 for 90 days after its discontinuation. Females must agree to refrain from donating ova while on CC-92480 for 28 days after its discontinuation.
  3. All subjects must agree to refrain from donating blood while on CC-92480 and for 28 days after its discontinuation.

Exclusion Criteria:

  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-SLAM-7) ≤ 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.

Additional Trial Information

Phase 1/2

Enrollment: 201 patients (estimated)

View More

Published Results

Mezigdomide (CC-92480), a Potent, Novel Cereblon E3 Ligase Modulator (CELMoD), Combined with Dexamethasone (DEX) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results from the Dose-Expansion Phase of the CC-92480-MM-001 Trial

December 11, 2022

As of May 24, 2022, 101 pts had received MEZI + DEX at the RP2D. Median age was 67 (range 42–85) years, median time since initial diagnosis was 7.4 (1.1–37.0) years, and 20.8% of pts had ISS stage III at study entry. Plasmacytomas were present in 38.6% of pts and 36/101 pts had high-risk cytogenetics (55/101 pts were not evaluable). Median number of prior regimens was 6 (range 3–15). Prior therapies included stem cell transplantation (77.2%) and anti-BCMA therapy (29.7%) (Table 1). All pts were refractory to last myeloma regimen and triple-class refractory (refractory to an IMiD agent [LEN/POM], a PI, and an anti-CD38 mAb), and 39.6% of pts were refractory to LEN, POM, ≥ 2 PIs, and an anti-CD38 mAb. Median follow-up was 5.8 (range 0.5–19.0) months, with a median number of 4 (1–18) cycles received and 23 (22.8%) pts continued on treatment. The main reason for discontinuation was progressive disease (50.5%).

ORR was 39.6%, with 2 (2.0%) stringent complete responses, 3 (3.0%) complete responses, 18 (17.8%) very good partial responses, and 17 (16.8%) partial responses (Table 2). While data are not yet mature, the preliminary median duration of response was 8.3 (95% confidence interval [CI] 5.4–not reached) months and median progression-free survival was 4.6 (95% CI 3.2–6.3) months. ORR was 30.8% in pts with plasmacytomas (N = 39) and 50.0% in pts with prior anti-BCMA therapy (N = 30).

Grade (Gr) 3/4 treatment-emergent adverse events (TEAEs) were reported in 90 (89.1%) pts. Most frequent (≥ 20% pts) hematologic Gr 3/4 TEAEs were neutropenia (74.3%, with 14.9% febrile neutropenia), anemia (32.7%), and thrombocytopenia (25.7%). Gr 3/4 infections were observed in 32.7% of pts; Gr 3/4 pneumonia and COVID-19 were present in 9.9% and 5.0% of pts, respectively. The occurrence of other Gr 3/4 non-hematologic TEAEs was generally low, including gastrointestinal disorders (5.9%), fatigue (4.0%), and rash (1.0%). Seventy-two (71.3%) pts and 29 (28.7%) had MEZI dose interruptions and reductions due to TEAEs, respectively; 6 (5.9%) pts discontinued MEZI due to TEAEs, with 1 pt due to hematological TEAEs.

First-in-human phase I study of the novel CELMoD agent CC-92480 combined with dexamethasone (DEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM)

June 01, 2020

  • As of Dec 24, 2019, 66 pts had received CC-92480 + dexamethasone.
  • Most frequent grade 3–4 treatment-emergent adverse events included neutropenia (53%), infections (30%), anemia (29%), and thrombocytopenia (17%), with 9% grade 3 fatigue.
  • Overall response rate (ORR) was 21% (9 very good partial responses [VGPRs]; 5 PRs) for efficacy evaluable population (n = 66).

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.


City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting



Winship Cancer Institute of Emory University

Atlanta, GA

Open and Accepting


Dana-Farber Cancer Institute

Boston, MA

Open and Accepting


Barbara Ann Karmanos Cancer Institute Wayne State University

Detroit, MI

Open and Accepting

New York

Roswell Park Cancer Institute

Buffalo, NY

Open and Accepting


West Penn Hospital (Allegheny Health Network)

Pittsburgh, PA

Not Yet Accepting

South Carolina

Gibbs Cancer Center and Research Spartanburg Regional Healthcare System

Spartanburg, SC

Not Yet Accepting


Sarah Cannon TriStar Centennial Medical Center

Nashville, TN

Open and Accepting


MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting


University of Washington School of Medicine

Seattle, WA

Open and Accepting

Trial Links

Read the latest news and updates on this trial.

CELMoD CC-92480/Dexamethasone Combo Shows Early Activity in Relapsed/Refractory Myeloma

December 06, 2020

CC-92480, a novel oral cereblon E3 ligase modulator (CELMoD) agent, plus dexamethasone demonstrated immunomodulatory activity across all dose levels examined in patients with relapsed/refractory multiple myeloma, according to data from the first portion of the ongoing phase 1 CC-92480-MM-001 trial (NCT03374085) presented during the 2020 ASH Annual Meeting & Exposition.

Read more
Interested in this trial?
  • Call us today 😀 keyboard_arrow_right

    We know how difficult and confusing this process can be. If you are interested in this clinical trial or have questions, you can call us at any time. You can also send us a direct message with questions.

    (888) 828-2206
  • If you are interested in keeping an eye on this trial, you can add it to your list of favorite trials. We'll send you alerts when this trial is updated.

  • Talk to your doctor keyboard_arrow_right

    You can print an overview of this trial to take in to your next appointment. Your doctor can help you understand if this trial may be right for you.

Still need help? Send us a message

SparkCures Verified

SparkCures is working closely with Celgene Corporation, a wholly owned subsidiary of Bristol Myers Squibb to provide the most up-to-date information on this clinical trial. Use the button above to add this trial to your list of favorites.

Learn more about how we work with trial sponsors