Dose-Escalation Study of cevostamab (BFCR4350A) in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)

Overview

About this study

This is a phase I, multicenter, open-label, dose-escalation study of cevostamab (BFCR4350A) administered as a single agent by IV infusion to participants with relapsed or refractory multiple myeloma (R/R MM).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Signed Informed Consent Form(s).
  • Age ≥ 18 years at time of signing Informed Consent Form.
  • Ability to comply with the study protocol, in the investigator's judgment.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Life expectancy of at least 12 weeks.
  • Patients must have R/R MM for which no established therapy for MM is appropriate and available or be intolerant to those established therapies.
  • Agreement to provide bone marrow biopsy and aspirate samples.
  • Adverse events from prior anti-cancer therapy resolved to Grade ≤ 1 with the following exceptions:
    • Any grade alopecia;
    • Peripheral sensory or motor neuropathy must have resolved to Grade ≤ 2.
  • Measurable disease defined as at least one of the following:
    • Serum monoclonal protein (M-protein) ≥ 0.5 g/dL (≥ 5 g/L);
    • Urine M-protein ≥ 200 mg/24 hr;
    • Serum free light chain (SFLC) assay.
  • Laboratory values as follows:
  • Hepatic function
    • AST and ALT ≤ 3 ≤ ULN
    • Total bilirubin ≤ 1.5 x ULN;
    • patients with a documented history of Gilbert syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible.
  • Hematologic function (requirement prior to first dose of cevostamab):
    • Platelet count ≥ 50,000/mm^3 without transfusion within 7 days prior to first dose;
    • ANC ≥ 1000/mm^3;
    • Total hemoglobin ≥ 8 g/dL;
    • Patients who do not meet criteria for hematologic function because of MM-related cytopenias (e.g., due to extensive marrow involvement by MM) may be enrolled into the study after discussion with and with the approval of the Medical Monitor.
    • Note: Patients may receive supportive care to meet hematologic function eligibility criteria (e.g., transfusions, G-CSF, etc.).
  • Creatinine ≤ 2.0 mL/dL and creatinine clearance (CrCl) ≥ 30 mL/min (either calculated or per 24-hr urine collection).
  • Serum calcium (corrected for albumin) level at or below Grade 1 hypercalcemia (patient may receive treatment for hypercalcemia to meet eligibility criteria).
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, as defined below:
    • Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of cevostamab and tocilizumab (if applicable);
    • A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a post-menopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus);
    • Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices;
    • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:
    • With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 60 days after the last dose of cevostamab and tocilizumab (if applicable) to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
    • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

  • Inability to comply with protocol-mandated hospitalization and activities restrictions.
  • Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the last dose of study drug.
  • Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug.
  • Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate as anti-cancer therapy within 4 weeks before first cevostamab infusion.
  • 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.
  • Prior treatment with chimeric antigen receptor (CAR) T-cell therapy within 12 weeks before first cevostamab infusion.
  • Known treatment-related, immune-mediated adverse events associated with prior immunotherapeutic agents as follows:
    • Prior PD-L1/PD-1 or CTLA-4 inhibitor: Grade ≥ 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy;
    • Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation.
    • Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first cevostamab infusion;
    • Autologous stem cell transplantation (SCT) within 100 days prior to first cevostamab infusion;
    • Prior allogeneic SCT;
    • Absolute plasma cell count exceeding 500/µL or 5% of the peripheral blood white cells;
    • Prior solid organ transplantation.
    • 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;
    • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study;
    • Patients with history of confirmed progressive multifocal leukoencephalopathy;
    • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins);
    • Patients with known history of amyloidosis (e.g., positive Congo Red stain or equivalent in tissue biopsy);
    • Patients with lesions in proximity of vital organs that may develop sudden decompensation/ deterioration in the setting of a tumor flare;
    • History of other malignancy that could affect compliance with the protocol or interpretation of results;
    • Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are allowed;
    • Patients with a malignancy that has been treated with curative intent will also be allowed if the malignancy has been in remission without treatment for ≥ 2 years prior to first cevostamab infusion;
    • Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM;
    • Patients 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;
    • Patients with a history of epilepsy who have had no seizures in the past 2 years while not receiving any anti-epileptic medications are allowed.
  • 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 patient's ability to adequately respond to a CRS event.
  • Symptomatic active pulmonary disease requiring supplemental oxygen.
  • 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.
  • Known or suspected chronic active EBV infection. Guidelines for diagnosing chronic active EBV infection are provided by Okano et al. (2005).
  • Recent major surgery within 4 weeks prior to first cevostamab infusion.
  • Protocol-mandated procedures (e.g., bone marrow biopsies) are permitted.
  • Positive serologic or PCR test results for acute or chronic HBV infection.
  • Patients whose HBV infection status cannot be determined by serologic test results (www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf) must be negative for HBV by PCR to be eligible for study participation.
  • Acute or chronic HCV infection.
  • Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation.
  • Known history of HIV seropositivity.
  • 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.
    • Influenza vaccination should be given during influenza season (approximately October to May in the Northern Hemisphere; approximately May to October in the Southern Hemisphere). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) at any time during the study treatment period;
    • SARS-CoV-2 vaccines, when available, may be given in accordance with the approved/authorized vaccine label and official/local immunization guidance, with approval of the Medical Monitor. SARS-CoV-2 vaccines must not be administered within 1 week before first study treatment or during Cycle 1;
    • Investigators should review the vaccination status of potential study patients 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.
  • Received systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, 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 and, if applicable, tocilizumab premedication prior to first dose of cevostamab.
  • Patients who received acute, low-dose, systemic immunosuppressant medications (e.g., single dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval of the Medical Monitor.
  • The use of inhaled corticosteroids is permitted.
  • The use of mineralocorticoids for management of orthostatic hypotension is permitted.
  • The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted.
  • History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment.
  • Any medical condition or abnormality in clinical laboratory tests that, in the investigator's or Medical Monitor's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Rafael Fonseca, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20397707

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