| Eligibility |
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 (?/?) 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 184 days after the last dose of CC-92480.
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 94 days following CC-92480 last dose 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 94 days after
the last dose of CC-92480. Females must agree to refrain from donating ova while on
CC-92480 for 184 days after last dose.
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-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.
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