| Eligibility |
Inclusion Criteria:
1. Signed Informed Consent Form(s)
2. Age =18 years at time of signing Informed Consent Form
3. Ability to comply with the study protocol
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
5. Life expectancy of at least 12 weeks
6. Participants must have relapsed and/or refractory multiple myeloma with at least 4
prior lines of therapy that must include a proteasome inhibitor, immunomodulatory drug
(IMiD), and anti-CD38 antibody, and have received a BCMA-directed CAR T cell product
as standard of care (i.e. not on a clinical trial) between 6 and 10 weeks prior to
enrollment, and have not had progressive disease by IMWG criteria since CAR T cell
infusion. Patients who have received out-of-specification CAR T cell products are not
eligible.
7. Agreement to provide bone marrow biopsy and aspirate samples
8. Non-hematologic adverse events from prior anti-cancer therapy resolved to Grade = 1,
with the certain exceptions.
9. Measurable disease is not required for study entry
10. Laboratory values as follows:
a. Hepatic function i. AST and ALT = 3 x ULN ii. Total bilirubin = 1.5 x ULN; b.
Hematologic function (cevostamab criteria should be met both at screening (to
determine eligibility), as well as on Cycle1, Day 1) i. Platelet count = 50,000/mm3
without transfusion within 7 days prior to first dose ii. ANC = 1000/mm3 iii. Total
hemoglobin = 7 g/dL c. Creatinine clearance (CrCl) = 30 mL/min d. Serum calcium
(corrected for albumin) level at or below Grade 1 hypercalcemia
11. For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures, as defined in the protocol.
12. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
a condom, and agreement to refrain from donating sperm, as defined in the protocol.
Exclusion Criteria:
1. Inability to comply with protocol-mandated hospitalization and activities restrictions
2. Pregnant or breastfeeding, or intending to become pregnant during the study or within
3 months after the last dose of study drug a. Women of childbearing potential must
have a negative serum pregnancy test result within 14 days prior to initiation of
study drug.
3. Participants who had = Grade 3 cytokine release syndrome (CRS) or immune effector
cell-associated neurotoxicity syndrome (ICANS) by ASTCT criteria, or any grade
macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH)after CAR-T
therapy are excluded
4. Participants who had any grade movement and/or neurocognitive disorder attributed to
CAR T cells are excluded.
5. Prior treatment with systemic immunotherapeutic agents, including, but not limited to,
cytokine therapy and anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeutic antibodies,
within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first
cevostamab infusion
6. Known treatment-related, immune-mediated adverse events associated with prior
immunotherapeutic agents as in the protocol.
7. Treatment with any chemotherapeutic agent, or any other anti-cancer agent
(investigational or otherwise) during the time period between CAR T cell infusion and
first cevostamab infusion, with the following exceptions:
1. Therapies used for treatment of CAR T cell-related toxicities (e.g. steroids,
cyclophosphamide) will not be a cause for exclusion, as long as washout period
listed below (2 weeks) is met
2. Short course palliative radiation post-CAR T cell therapy (e.g. for severe bone
pain, impending fracture) is allowed as long as completed at least 1 week prior
to first dose of cevostamab.
8. Received systemic immunosuppressive medications (including, but not limited to,
steroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, tocilizumab,
siltuximab, anakinra, ruxolitinib, and anti-tumor necrosis factor agents), with the
exception of corticosteroid treatment = 10 mg/day prednisone or equivalent, within 2
weeks prior to first dose of cevostamab a. Participants who received acute, low-dose,
systemic immunosuppressant medications (e.g., single dose of dexamethasone for nausea)
may be enrolled in the study.
i. The use of inhaled corticosteroids is permitted. ii. The use of mineralocorticoids
for management of orthostatic hypotension is permitted.
iii. The use of physiologic doses of corticosteroids for management of adrenal
insufficiency is permitted.
9. Autologous stem cell transplantation (SCT) within 100 days prior to first cevostamab
infusion
10. Prior allogeneic SCT within 12 months prior to first cevostamab infusion. Participants
with prior allogeneic SCT must have no evidence for active graft-versus-host-disease
(GVHD) and be off all therapy for GVHD for at least 3 months prior to first cevostamab
infusion.
11. Prior solid organ transplantation
12. History of autoimmune disease, including, but not limited to, myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome,
multiple sclerosis, vasculitis, or glomerulonephritis
1. Participants with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid replacement hormone may be eligible for this study.
2. Participants with history of immune thromobocytopenic purpura (ITP), autoimmune
hemolytic anemia, or other immune-mediated conditions that solely affect blood
counts, as long as these conditions are not active at the time of enrollment and
subjects otherwise meet hematologic parameters for eligibility, may be eligible
with approval from Sponsor Medical Director.
13. Participants with history of confirmed progressive multifocal leukoencephalopathy
14. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
(or recombinant antibody-related fusion proteins)
15. History of other malignancy that could affect compliance with the protocol or
interpretation of results
1. Participants with a history of curatively treated basal or squamous cell
carcinoma of the skin or in situ carcinoma of the cervix are allowed.
2. Participants with a malignancy that has been treated with curative intent will
also be allowed if the malignancy has been in remission prior to first cevostamab
infusion.
16. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis,
neurodegenerative disease, or CNS involvement by MM
1. Participants with a history of stroke who have not experienced a stroke or
transient ischemic attack in the past 2 years and have no residual neurologic
deficits as judged by the investigator are allowed.
2. Participants with a history of epilepsy who have had no seizures in the past 2
years while not receiving any anti-epileptic medications are allowed.
17. Significant cardiovascular disease (such as, but not limited to, New York Heart
Association Class III or IV cardiac disease, myocardial infarction within the last 6
months, uncontrolled arrhythmias, or unstable angina) that may limit a subject's
ability to adequately tolerate a cytokine release syndrome (CRS) event
18. Symptomatic active pulmonary disease or requiring supplemental oxygen
19. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) at study enrollment, or any major episode
of infection requiring treatment with IV antibiotics within 14 days prior to first
cevostamab infusion. Empiric or prophylactic antibiotics administered during
neutropenia or neutropenic fever without microbiologic evidence of infection do not
exclude subjects.
a. Participants with asymptomatic CMV reactivation (i.e. positive CMV PCR) found at
screening may enroll after discussion with the Medical Director.
20. Known or suspected chronic active Epstein-Barr virus (EBV) infection. Guidelines for
diagnosing chronic active EBV infection are provided by Okano et al. (2005).
21. Recent major surgery within 4 weeks prior to first cevostamab infusion
a. Protocol-mandated procedures (e.g., bone marrow biopsies) are permitted.
22. Positive serologic or polymerase chain reaction (PCR) test results for acute or
chronic hepatitis B virus (HBV) infection
a. Participants whose HBV infection status cannot be determined by serologic test
results must be negative for HBV by PCR to be eligible for study participation.
23. Acute or chronic hepatitis C virus (HCV) infection
a. Participants who are positive for HCV antibody must be negative for HCV by PCR to
be eligible for study participation.
24. Known history of HIV seropositivity
25. Administration of a live, attenuated vaccine within 4 weeks before first cevostamab
infusion or anticipation that such a live attenuated vaccine will be required during
the study
1. Influenza vaccination should be given during influenza season (approximately
October to May in the Northern Hemisphere). Subjects must not receive live,
attenuated influenza vaccine (e.g., FluMist®) at any time during the study
treatment period.
2. SARS-CoV-2 vaccines may be given in accordance with the approved/authorized
vaccine label and official/local immunization guidance. SARS-CoV-2 vaccines must
not be administered within 1 week before first study treatment or during Cycle 1.
3. Investigators should review the vaccination status of potential study subjects
being considered for this study and follow the U.S. Centers for Disease Control
and Prevention guidelines for adult vaccination with any other non-live vaccines
intended to prevent infectious diseases prior to study.
26. Any medical condition or abnormality in clinical laboratory tests that, in the Medical
Director's judgment, precludes the subject's safe participation in and completion of
the study, or which could affect compliance with the protocol or interpretation of
results.
|
