Clinical Trials

Inclusion Criteria:

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
• Age ≥ 18 years at the time of signing the informed consent.
• Multiple myeloma meeting the following criteria:
  • Pathologically-documented diagnosis of multiple myeloma that is relapsed or is refractory as defined by the following:
    • Relapsed after ≥ 2 lines of prior therapy that must include a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and, where approved and available, a CD38-directed cytolytic antibody in any order during the course of treatment OR refractory to PI, IMiD and CD38-directed cytolytic antibody;
    • Subjects who could not tolerate a PI, IMiDs, or a CD38-directed cytolytic antibody are eligible to enroll in the study.
• Measurable disease, defined by 1 or more of the following at time of screening.
  • Note: extramedullary disease in the absence of medullary disease will be allowed in Group B of dose expansion):
    • a serum M protein > 0.5 g/dL measured by serum protein electrophoresis (SPEP);
    • urinary M protein excretion > 200 mg/24 hours;
    • sFLC measurement > 10 mg/dL, provided that the sFLC ratio is abnormal (< 0.26 or > 1.65) as per IMWG response criteria.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Life expectancy of at least 3 months as per investigator`s judgment at time of screening.
• Hematological function without transfusion support (within 7 days from screening assessment) as follows:
  • absolute neutrophil count (ANC) ≥ 1.0 x 109/L (without growth factor support);
  • platelet count ≥ 25 x 109/L (without transfusions); platelet count between 25 and 50 x 109/L at time of enrollment requires agreement by both the Investigator and Amgen Medical Monitor of acceptability before enrollment can be approved;
  • hemoglobin > 8 g/dL (> 80 g/L) (without transfusion or growth factor support).
• Renal function as follows:
  • calculated or measured creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation; OR
  • via 24-hour urine collection with plasma and urine creatinine concentrations.
• Hepatic function as follows:
  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN);
  • total bilirubin (TBIL) < 1.5 x ULN (unless considered due to Gilbert’s syndrome).

Exclusion Criteria:

• Extramedullary disease in the absence of any measurable medullary involvement (exception: inclusion of these subjects will be allowed in Group C of dose expansion).
• Known central nervous system involvement by multiple myeloma.
• Previously received an allogeneic stem cell transplant and the occurrence of 1 or more of the following:
  • received the transplant within 6 months prior to study day 1;
  • received immunosuppressive therapy within the last 3 months prior to study day 1;
  • any active acute graft versus host disease (GvHD), grade 2 to 4, according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment;
  • any systemic therapy against GvHD within 2 weeks prior to start of investigational product treatment.
• Autologous stem cell transplantation less than 90 days prior to study day 1.
• Multiple myeloma with IgM subtype.
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
• Known history of primary plasma cell leukemia or evidence of primary or secondary plasma cell leukemia at the time of screening.
• Waldenstrom’s macroglobulinemia.
• Amyloidosis.
• Treatment with systemic immune modulators including, but not limited to, nontopical systemic corticosteroids (unless the dose is ≤ 10 mg/day prednisone or equivalent), cyclosporine, and tacrolimus within 2 weeks before study day 1.
• Last anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) < 2 weeks prior to study day 1.
• Last treatment with a therapeutic antibody less than 4 weeks prior to study day 1.
• Systemic radiation therapy within 28 days prior to study day 1. Focal radiotherapy within 14 days prior to study day 1.
• Major surgery within 28 days prior to study day 1.
• Prior treatment with any drug or construct that targets BCMA on tumor cells (eg, other bispecific antibody constructs, antibody drug conjugates, or CAR-T cells).
• Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded.
• Treatment with medications known to cause QTc interval prolongation within the washout periods described in Appendix E unless approved by the Amgen medical monitor.
• Unresolved toxicities from prior anticancer therapy, defined as not having resolved to CTCAE version 4.0 grade 1 or to levels dictated in the eligibility criteria with the exception of grade 2 peripheral neuropathy, alopecia or toxicities from prior anticancer therapy that are considered irreversible (defined as having been present and stable for > 4 weeks) which may be allowed if they are not otherwise described in the exclusion criteria and there is agreement to allow by both the investigator and Amgen medical monitor.
• Clinically-not controlled chronic or ongoing infectious disease requiring treatment at the time of study day 1 or within the 14 days before study day 1.
• Active hepatitis B and C based on the following results:
  • Positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B);
  • Negative HepBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B;
  • Positive Hepatitis C virus antibody (HepCAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
• Positive results for human immunodeficiency virus (HIV).
• Baseline ECG QTc > 470 msec (applying Fridericia correction), defined as the average of individual baseline ECGs.
• History of malignancy other than multiple myeloma within the past 5 years with the following exceptions:
  • Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician;
  • Adequately-treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
  • Adequately-treated cervical carcinoma in situ without evidence of disease;
  • Breast ductal carcinoma in situ with full surgical resection (i.e., negative margins) and without evidence of disease;
  • Prostate cancer with a Gleason score less than 7 with undetectable prostate specific antigen (PSA) over 12 months;
  • Treated medullary or papillary thyroid cancer;
  • Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ;
  • Similar neoplastic conditions with an expectation of > 95% five-year disease-free survival.
• Known hypersensitivity to immunoglobulins or to any components of the study drug.
• Current or known history of autoimmune diseases requiring systemic treatment in past 5 years.
• Males and females of reproductive potential who are unwilling to practice highly effective method(s) of birth control while on study through 75 days (females) and 135 days (males) after receiving the last dose of study drug. Highly effective methods of birth control include sexual abstinence (males, females); vasectomy; bilateral tubal ligation/occlusion; or a condom with spermicide (males) in combination with hormonal birth control or intrauterine device (IUD) (females).
• Females who are lactating/breastfeeding or who plan to breastfeed while on study through 75 days after receiving the last dose of study drug.
• Females with a positive pregnancy test.
• Females planning to become pregnant while on study through 75 days after receiving the last dose of study drug.
• Males who are unwilling to abstain from sperm donation while on study through 135 days after receiving the last dose of study drug.
• Subjects likely to not be available to complete all protocol-required study visits or procedures including BM aspirates/biopsies, and/or to comply with all required study procedures to the best of the subject and investigator’s knowledge.
• History or evidence of any other clinically-significant disorder, condition or disease (e.g., symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring therapy at time of screening) with the exception of those outlined above that, in the opinion of the investigator or Amgen medical monitor, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.