First In Human (FIH) Study of REGN5459 in Patients With Relapsed or Refractory Multiple Myeloma (MM)


About this study

The purpose of this study is to assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine a recommended phase 2 dose regimen (RP2DR) (defined as either a maximum tolerated dose regimen [MTDR] or biologically effective dose regimen [BEDR]) of REGN5459 as monotherapy in patients with relapsed or refractory multiple myeloma (MM) who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit. 

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:

  • Age 18 years or greater.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
  • Confirmed diagnosis of active MM by IMWG diagnostic criteria (Rajkumar, 2014).
  • Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria.
  • Measurable disease is defined as 1 or more of the following:
    • Serum M-protein ≥ 1 g/dL;
    • Urine M-protein ≥ 200 mg/24-hour; and/or
    • FLC assay with involved FLC level ≥ 10 mg/dL with an abnormal serum FLC ratio:
      • A patient with Immunoglobulin A (IgA) myeloma but without measurable M-protein may be enrolled if quantitative IgA levels are ≥ 400 mg/dL and can be followed longitudinally;
      • A patient with non-secretory MM may be considered for enrollment after discussion with the sponsor that includes the feasibility of an individualized plan for response assessment.
  • Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease, or intolerance of the therapy, and including either:
    • Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a proteasome inhibitor, an IMiD, and an anti-CD38 antibody; OR
    • Progression on or after an anti-CD38 antibody and having disease that is "double refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor. Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
  • Adequate hematologic function as measured by:
    • Platelet count > 50 x 10^9/L. A patient may not have received a platelet transfusion within 7 days to meet this platelet eligibility requirement;
    • ANC > 1.0 x 10^9/L. A patient may not have received granulocyte colony stimulating factor (G-CSF) within 2 days to meet this absolute neutrophil count eligibility requirement;
    • Hemoglobin > 8.0 g/dL.
  • Adequate hepatic function, defined as:
    • Total bilirubin ≤ 1.5 x ULN;
    • Transaminase (ALT, AST) ≤ 2.5 x ULN;
    • Alkaline phosphatase ≤ 2.5 x ULN.
      • Patients with Gilbert syndrome do not need to meet this total bilirubin requirement provided that the total bilirubin is unchanged from the baseline value.
    • Serum creatinine clearance by Cockcroft-Gault >30 mL/min.
      • A patient with a creatinine clearance by Cockcroft-Gault who does not meet eligibility criteria may be considered for enrollment if a measured creatinine clearance (based on 24-hour urine collection or other reliable method) is >30 mL/min.
  • If previously treated with CAR T therapy or any gene therapy products, patients must have recovered from the toxicities of this therapy.
  • Life expectancy of at least 6 months.
  • Willing and able to comply with clinic visits and study-related procedures, including serial bone marrow evaluations according to the protocol schedule.
    • A bone marrow aspirate and biopsy, or other tissue infiltrated with malignant plasma cells, must be provided at screening for evaluation of BCMA levels in malignant cells, but demonstration of BCMA levels will not be required for enrollment.
  • Provide informed consent signed by the study patient.
  • Able to understand and complete study-related questionnaires.

Exclusion Criteria:

  • Diagnosis of plasma cell leukemia, amyloid light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  • Patients with known MM brain lesions or meningeal involvement.
  • History of neurodegenerative condition or CNS movement disorder, or patients with a history of seizure within 12 months before study enrollment are excluded
  • Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (multi-gated acquisition scan [MUGA])
  • Continuous systemic corticosteroid treatment with >10 mg per day of prednisone or anti-inflammatory equivalent within 72 hours of start of study drug.
  • Vaccination within 28 days before first study drug administration with a vector that has replicative potential.
  • Treatment with any systemic standard or investigational anti-myeloma therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter.
  • Prior treatment with any anti-BCMA antibody (including antibody-drug conjugate or bispecific antibody) or BCMA-directed CAR T therapy.
  • Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first administration of study drug.
    • A patient being screened for R5459-ONC-1888 who has documented or suspected ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection should not be enrolled in the study.
    • A patient being screened for R5459-ONC-1888 who had documented or suspected SARS-CoV-2 may be enrolled per the investigator’s medical judgment if the patient has:
      • Recovered from COVID-19 (ie, all COVID-19-related symptoms and major clinical findings that can potentially affect the safety of the patient have resolved), and:
      • It is advisable that 2 repeat COVID-19 polymerase chain reaction (PCR) tests, or equivalent test depending on regional recommendations, be conducted to confirm that the patient is negative for SAVS-CoV-2.
      • If COVID-19 PCR testing is not feasible, it is advised that at least 3 months have transpired since the initial diagnosis.
  • Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; or other uncontrolled infection.
    • Patients with HIV who have controlled infection (undetectable viral load and CD4 count above 350 cells/microliter either spontaneously or on a stable antiviral regimen) are permitted.
    • Patients with hepatitis B (Hepatitis B Surface Antigen Test positive [HepBsAg+]) who have controlled infection (serum HBV DNA polymerase chain reaction [PCR] that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted.
    • Patients who are HCV antibody-positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
  • Has known allergy or hypersensitivity to components of REGN5459.
  • Known hypersensitivity to both allopurinol and rasburicase.
  • History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment.
  • Member of the clinical site study team or his/her immediate family, unless prior approval granted by the sponsor.
  • Women of childbearing potential (WOCBP) with a positive serum beta-human chorionic gonadotropin (β-hCG) pregnancy test are ineligible for this study.
  • Patients who are committed to an institution by an order issued either by the judicial or the administrative authorities.
  • Pregnant or breastfeeding women.
  • Women of childbearing potential* and men** who are unwilling to practice highly effective contraception before the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose.
    • Highly effective contraceptive measures for women include:
      • stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles before screening 
      • intrauterine device (IUD); intrauterine hormone-releasing system (IUS)
      • bilateral tubal ligation
      • vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the study participant and that the partner has obtained medical assessment of surgical success for the procedure)
      • and/or sexual abstinence†, ‡.
  • Women of childbearing potential are defined as women who are fertile following menarche until becoming post-menopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
  • A post-menopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a post-menopausal state. The above definitions are according to Clinical Trial Facilitation Group (CTFG) guidance.

**Highly effective contraceptive measures for men include condoms or sexual abstinence, unless vasectomized (which has been medically assessed for surgical success) †, ‡.

†Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.

‡Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.

  • Another malignancy in the past 5 years, except for non-melanoma skin cancer that has undergone potentially curative therapy or in situ cervical carcinoma, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent.

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

Rochester, Minn.

Mayo Clinic principal investigator

Prashant Kapoor, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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