Inclusion Criteria:
Participants must satisfy the following criteria to be enrolled in the study:
1. Participant (male or female) is ≥ 18 years of age at the time of signing the informed
consent form (ICF).
2. Participant has a history of multiple myeloma (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. Participants 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 participants 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. Participant has an ECOG PS of 0-1.
5. Participants must have the following laboratory values (determined by local
laboratory):
- Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L without growth factor support for
7 days (14 days if pegfilgrastim)
- Platelets (plt) ≥ 75 x 10^9/L without transfusion for 7 days or plt ≥ 50 x 109/L
when BM plasma cells ≥ 50%.
- 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 participants with documented
Gilbert's syndrome).
- Estimated serum creatinine clearance of ≥ 60 mL/min
- International normalized ratio (INR) < 1.5 x ULN and activated partial
thromboplastin time (APTT) < 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. Participant must agree to ongoing pregnancy testing during the
course of the study, and after end of study treatment. This applies even if the
participant practices true abstinence from heterosexual contact. The participant
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.
- Agree to ongoing pregnancy testing during the course of the study, and after the
end of study treatment. This applies even if the participant practices true
abstinence2 from heterosexual contact.
- 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.
7. Participant 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 participant from enrollment:
1. In Part A only, participant has received prior therapy directed at BCMA including, but
not limited to, antibody-drug conjugates (BCMA-ADC), bispecific T cell-engaging
antibodies or molecules, or BCMA-directed T cell therapy (eg, BCMA chimeric antigen
receptor [CAR] T cells).
2. Participant has symptomatic central nervous system involvement of MM.
3. Participant has nonsecretory MM, plasma cell leukemia, Waldenstrom's
macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy,
monoclonal protein, and skin changes), or amyloidosis.
4. Participants 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. Participant had a prior autologous stem cell transplant ≤ 3 months prior to starting
CC-99712.
6. Participant 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. Participant had a prior chimeric antigen receptor T (CAR T) cell product ≤ 4 weeks
prior to starting CC-99712.
8. Participant 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. Participant had major surgery ≤ 2 weeks prior to starting CC-99712. Participants must
have recovered from any clinically significant effects of recent surgery.
10. Participant is a pregnant or lactating female.
11. Participant has known human immunodeficiency virus (HIV) infection.
12. Participant has known history of chronic, active hepatitis B or C virus (HBV/HCV)
infection.
13. Participant requires ongoing treatment with chronic, therapeutic dosing of
anti-coagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors).
14. Participant has a history of concurrent second cancers requiring active, ongoing
systemic treatment.
15. Participant has known history of cirrhosis or has clinically significant liver or
biliary disease. Participants 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. Participant has a history of clinically significant corneal disease requiring therapy
or ongoing active corneal disease.
17. Participant 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).
18. Participant has any significant medical condition, laboratory abnormality, or
psychiatric illness that would prevent the participant from participating in the
study.
19. Participant has any condition including the presence of laboratory abnormalities, such
as active or uncontrolled infection, which places the participant at unacceptable risk
if he/she were to participate in the study.
20. Participant has any condition that confounds the ability to interpret data from the
study.
21. Participant has confirmed extramedullary plasmacytoma in pulmonary, cardiac, or
hepatic systems.
22. Participant has documented malabsorptive syndromes including enteropathies,
gastroenteritis (acute or chronic) or diarrhea (acute or chronic) with active
treatment.
23. Participant has previous SARS-CoV-2 infection within 10 days for mild or asymptomatic
infections or 20 days for severe/critical illness prior to C1D1.
• Acute symptoms must have resolved and based on investigator assessment in
consultation with the medical monitor, there are no sequelae that would place the
participant at a higher risk of receiving study treatment.
24. Participant has previous SARS-CoV-2 vaccine within 14 days of C1D1. For vaccines
requiring more than one dose, the full series (eg, both doses of a two-dose series)
should be completed at least 14 days prior to C1D1 when feasible and when a delay in
C1D1 would not put the study participant at risk.
