This is a multicenter, open-label, dose-escalation Phase 1b study of AEVI-007 in subjects
with relapsed or refractory Multiple Myeloma.
The objectives of the study are to evaluate the safety, pharmacokinetics and pharmacodynamics
1. Subject has active R/R multiple myeloma.
2. Subject has measurable myeloma based on any of the following:
- Serum M-protein > 0.5 g/dL
- Urine M-protein > 200 mg/24 hours
- Serum free light chains > 10 mg/dL
- Measurable plasmacytoma or extramedullary disease
3. Subject has active myeloma despite prior therapy with a proteasome inhibitor, an
immunomodulatory agent and an anti-CD38 antibody.
Note: Subject must not be a candidate for regimens known to provide clinical benefit.
4. Subject has an Eastern Cooperative Oncology Group performance status (ECOG PS) score
of 0 or 1.
5. Subject is > 18 years of age.
6. Subject has adequate hematopoietic, renal and hepatic function, defined as:
- Absolute neutrophil count > 1,000/μL; platelet count > 75,000/μL in patients with
< 50% marrow involvement
- Absolute neutrophil count > 750/μL; platelet count > 50,000/μL in patients with
>50% marrow involvement
- Serum creatinine < 2.5 mg/dL or calculated creatinine clearance of > 30 mL/min
according to the Cockcroft-Gault equation
- Aspartate transaminase/alanine transaminase ≤2.5× the upper limit of normal (ULN)
and total bilirubin < 2× the ULN
7. If applicable, the subject has undergone prior autologous hematopoietic stem cell
transplantation more than 100 days prior to the Screening Visit.
8. Female patients of childbearing potential who are heterosexually active and male
patients with female sexual partners of childbearing potential must agree to use an
effective method of contraception (eg, oral contraceptives, double-barrier methods
such as a condom and a diaphragm, intrauterine device) or abstain from sexual activity
during the study and for 220 days (5 half-lives) following the last dose of study
medication, or to abstain from sexual intercourse for this duration of study
participation. A woman not of childbearing potential is one who has undergone
bilateral oophorectomies or who is post-menopausal, defined as the absence of
menstrual periods for 12 consecutive months.
9. Subject has provided written informed consent for this study.
1. Subject has currently active infection requiring use of systemic antimicrobial
2. Subject has received corticosteroids (>10 mg/daily prednisone or equivalent) or
chemotherapy within 2 weeks of study drugs (4 weeks for nitrosourea, melphalan or
3. Subject has hyperviscosity syndrome.
4. Subject has central nervous system involvement by myeloma, including leptomeningeal
5. Subject is judged to be at risk for impending fracture.
6. Subject has known amyloidosis or POEMS (Polyneuropathy, Organomegaly, Endocrinopathy,
Monoclonal protein, Skin changes) syndrome.
7. Subject had another malignancy within 1 year of study entry with high probability of
8. Subject is pregnant or lactating.
9. Subject has a history of, or tests positive for, hepatitis B, untreated hepatitis C or
human immunodeficiency virus (HIV). Subject with hepatitis C who has received a full
course of anti-viral therapy or who is currently receiving anti-viral therapy with
undetectable levels of hepatitis C RNA is eligible for the trial.
10. Subject has undergone major surgery or trauma within 4 weeks of study entry.
11. Subject has been previously treated with an anti IL 18 antibody.
12. Subject is currently taking immunomodulatory drugs, including pharmacologic doses of
systemic glucocorticoids (> 10 mg prednisone daily or equivalent), anti tumor necrosis
factor alpha (TNFα) antibodies, anti-IL-17 antibodies, anti IL 12/23 antibodies,
phosphodiesterase-4 (PDE-4) inhibitors, janus kinase (JAK) inhibitors, IL-6
inhibitors, rituximab, methotrexate, cyclosporine, mycophenolate.
13. Subject with known active autoimmune disorders including, but not limited to,
rheumatoid arthritis, lupus, systemic sclerosis, Sjogren's syndrome, psoriatic
arthritis, ulcerative colitis, Crohn's disease, vasculitis, multiple sclerosis.
Subjects with autoimmune endocrinopathies on stable doses of replacement hormone
therapy are eligible for the trial.
14. Subject has had a prior allogeneic transplant.
15. Subject has New York Heart Association (NYHA) Class III or IV Congestive Heart Failure
(CHF), myocardial infarction or acute coronary syndrome within 6 months prior to the
Screening Visit, ongoing angina pectoris, severe peripheral vascular disease, or any
other concomitant medical disorder that might interfere with the subject's
participation in the trial or interpretation of the study data.
16. Subject has psychiatric, substance abuse or social conditions that would interfere
with the subject's participation or cooperation with the requirements of the trial.
17. Subject has known hypersensitivity to any of the components of AEVI-007.