Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject (male or female) is ≥ 18 years of age at the time of signing the ICF.
2. Subject has a history of MM with relapsed and refractory disease, and must:
- Have disease that is nonresponsive while on their last antimyeloma therapy or
documented disease progression on or within 60 days from the last dose of their
last antimyeloma therapy; and,
- Must have received at least 3 prior MM treatment regimens. and,
- Must have received a proteasome inhibitor, an immunomodulatory agent and an
anti-CD38 antibody (eg, daratumumab); and,
- Should have failed treatment with or are intolerant to all established therapies.
3. Subjects must have measurable disease, including at least one of the criteria below:
- M-protein quantities ≥ 0.5 g/dL by sPEP or
- ≥ 200 mg/24 hours 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 patients without detectable 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.
4. Subject has an ECOG PS of 0-1.
5. Subjects must have the following laboratory values (determined by local laboratory):
- Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
- Platelets (plt) ≥ 75 x 10^9/L.
- Potassium within normal limits or correctable with supplements.
- Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤
2.5 x upper limit of normal (ULN).
- Serum bilirubin ≤ 1.5 x ULN (or ≤ 2.0 x ULN for subjects with documented
Gilbert's syndrome).
- Estimated serum creatinine clearance of ≥ 60 mL/min
- International normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time
(PTT) < 1.5 x ULN.
6. Females of childbearing potential (FCBP) must:
- 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, at least two effective contraceptive methods (oral, injectable,
or implantable hormonal contraceptive; tubal ligation; intra-uterine device;
barrier contraceptive with spermicide; or vasectomized partner), one of which
must be barrier, from signing the ICF, throughout the study, during dose
interruptions, and for up to 42 days following the last dose of CC-99712; and
- Have two negative pregnancy tests as verified by the Investigator prior to
starting CC-99712. Subject must agree to ongoing pregnancy testing during the
course of the study, and after end of study treatment. This applies even if the
subject practices true abstinence from heterosexual contact. The subject may not
receive IP until the Investigator has verified that the result of the pregnancy
test is negative.
- a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at
Screening
- a negative serum or urine pregnancy test (Investigator's discretion) within
72 hours prior to Cycle 1 Day -1 of study treatment, and within 72 hours
prior to Day -1 of every subsequent cycle (note that the Screening serum
pregnancy test can be used as the test prior to Day -1 study treatment if it
is performed within the prior 72 hours). A serum or urine pregnancy test
(investigators discretion) must also be performed at the end of study for
each FCBP.
- Avoid conceiving for 42 days after the last dose of CC-99712.7. Males must
practice true abstinence (which must be reviewed on a monthly basis) or agree to
use a condom (a latex condom is recommended) during sexual contact with a
pregnant female or a FCBP and will avoid conceiving from signing the ICF, while
participating in the study, during dose interruptions, and for at least 42 days
following CC-99712 discontinuation, even if he has undergone a successful
vasectomy.
8. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
1. In Part A only, subject has received prior investigational therapy directed at BCMA.
2. Subject has symptomatic central nervous system involvement of MM.
3. Subject has nonsecretory MM, plasma cell leukemia, Waldenstrom's macroglobulinemia,
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
skin changes), or amyloidosis.
4. Subjects with a history of class III or IV congestive heart failure (CHF) or severe
non-ischemic cardiomyopathy, unstable angina, myocardial infarction, or ventricular
arrhythmia within the previous 6 months prior to signing ICF.
5. Subject had a prior autologous stem cell transplant ≤ 3 months prior to starting
CC-99712.
6. Subject had a prior allogeneic stem cell transplant with either standard or reduced
intensity conditioning ≤ 6 months prior to starting CC-99712 or is on systemic
immunosuppression for graft-versus host disease.
7. Subject had a prior chimeric antigen receptor T (CAR T) cell product ≤ 4 weeks prior
to starting CC-99712.
8. Subject had a prior systemic cancer-directed treatments or investigational modalities
within 5 pharmacokinetic half-lives or 2 weeks prior to starting CC-99712, whichever
is longer. The only exception is emergency use of a short course of corticosteroids
(equivalent of dexamethasone 40 mg/day for a maximum 4 days) before treatment.
9. Subject had major surgery ≤ 2 weeks prior to starting CC-99712. Subjects must have
recovered from any clinically significant effects of recent surgery.
10. Subject is a pregnant or lactating female.
11. Subject has known human immunodeficiency virus (HIV) infection.
12. Subject has known history of chronic, active hepatitis B or C virus (HBV/HCV)
infection.
13. Subject requires ongoing treatment with chronic, therapeutic dosing of anti-coagulants
(eg, warfarin, low molecular weight heparin, Factor Xa inhibitors).
14. Subject has a history of concurrent second cancers requiring active, ongoing systemic
treatment.
15. Subject has known history of cirrhosis or has clinically significant liver or biliary
disease. Subjects with stable chronic liver or biliary disease (such as Gilbert's
syndrome, asymptomatic gallstones, or hepatobiliary involvement of malignancy) may
participate in the study, however, sponsor medical monitor must be contacted for a
discussion before enrollment.
16. Subject has a history of clinically significant corneal disease requiring therapy or
ongoing active corneal disease.
17. Subject has active peripheral neuropathy or neuropathic pain Grade 2 or higher, as
defined by the National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI-CTCAE v5.0).
