Relapsed/Refractory Multiple Myeloma
Conditions
Keywords
AMG 701, Relapsed/Refractory Multiple Myeloma, B-cell maturation antigen (BCMA)
Brief summary
A study to evaluate the safety and tolerability of subcutaneous (SC) AMG 701 in participants with relapsed or refractory multiple myeloma (RRMM) to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
Interventions
DRUGAMG 701
AMG 701 will be administered as SC or intravenous injection.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has provided informed consent prior to initiation of any study specific activities/procedures. * Age 18 years or older at the time of signing the informed consent. * Relapsed or relapsed and refractory multiple myeloma according to International Myeloma Working Group (IMWG) criteria. * Participants must have received ≥ 3 prior therapies that must include all approved and available therapies deemed eligible by the investigator, including at a minimum, a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and a CD38-directed antibody. Note: Participants may have received prior treatment targeting BCMA that is not AMG 701. * Participants must have measurable disease, defined by 1 or more of the following at time of screening : * A serum M protein ≥ 0.5 g/dL measured by serum protein electrophoresis (SPEP) * Urinary M protein excretion ≥ 200 mg/24 hours * Involved serum free light chain (sFLC) measurement ≥ 10 mg/dL, provided that SFLC ratio is abnormal 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 as follows: * Absolute neutrophil count ≥ 1.0 x 10\^9/L (without growth factor support) * Platelet count ≥ 50 x 10\^9/L (without transfusions within 7 days from screening assessment) * Hemoglobin ≥ 8.0 g/dL (transfusions permitted no later than 48 hours before screening) * 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) ≤ 2.5 x upper limit of normal (ULN) * Total bilirubin (TBIL) \< 1.5 x ULN (unless considered due to Gilbert's syndrome) * Cardiac function as follows: * Left ventricular ejection fraction ≥ 50% as assessed by transthoracic echocardiogram (TTE) or multigated acquisition (MUGA) scan. * Serum sodium, potassium, phosphorus, calcium, and magnesium must be within normal range or if outside normal range must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1 within 7 days of day 1. Participants not meeting these inclusion criteria may be treated with replacement therapy and re-screened up to 2 times at the discretion of the investigator. * Participants with prior COVID-19 infection or history of cardiovascular disease including coronary artery disease, significant valvular disease, cardiac arrhythmia, cardiomyopathy, or history of cardiac toxicity with prior therapy must have a cardiology consultation during screening with a clinical management plan during cytokine release syndrome (CRS) prior to cycle 1 day 1 therapy. * Participants with a history of COVID-19 infection must be discussed with the medical monitor prior to enrollment. Participants with a history of COVID-19 infection must have a negative quantitative polymerase chain reaction (PCR) test prior to enrollment.
Exclusion criteria
* Known central nervous system involvement by multiple myeloma. * Recent history of primary plasma cell leukemia (within last 6 months prior to enrollment) or evidence of primary or secondary plasma cell leukemia at the time of screening. * Waldenström macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes), or amyloidosis (participants with multiple myeloma with asymptomatic amyloid plaques found on biopsy would be eligible if all other criteria are met). * History or evidence of any of the following cardiovascular disorders: * Active congestive heart failure (New York Heart Association Class III to IV) * Symptomatic ischemia * Uncontrolled arrhythmias * Screening ECG with corrected QT interval (QTc) of \> 470 msec * Myocardial infarction within 12 months prior to study day 1 * History of malignancy other than multiple myeloma within the past 3 years with the following exceptions: * Malignancy treated with curative intent and with no known active disease present for at least 1 year before enrollment and felt to be at low risk for recurrence by the treating physician. * Adequately treated cervical carcinoma in situ without evidence of disease. * Breast ductal carcinoma in situ with full surgical resection (ie, negative margins) and without evidence of disease * Prostate cancer with a Gleason score \< 7 with undetectable prostate specific antigen 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% 5-year disease-free survival * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. * Clinically uncontrolled chronic or ongoing bacterial, fungal, viral, or other infectious disease at study day 1 or within 14 days before study day 1. * Positive result for human immunodeficiency virus (HIV). * 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: Either a positive hepatitis B surface antibody or a negative hepatitis B virus DNA by PCR result is necessary for enrollment * Positive hepatitis C virus antibody: Negative hepatitis C virus RNA by PCR result is necessary for enrollment * Unresolved toxicities from prior anticancer therapy, defined as not having resolved to CTCAE version 5.0 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants who experience dose-limiting toxicities (DLTs) | 28 days |
| Number of participants who experience one or more treatment-emergent adverse events (TEAEs) | up to approximately 9 months |
| Number of participants who experience one or more treatment-related TEAEs | up to approximately 9 months |
| Number of participants with abnormal changes in vital signs | up to approximately 9 months |
| Number of participants with abnormal changes in electrocardiograms (ECGs) findings | up to approximately 9 months |
| Number of participants with abnormal changes in clinical laboratory tests | up to approximately 9 months |
Secondary
| Measure | Time frame |
|---|---|
| Best overall response (BOR) | up to approximately 8 months |
| Time to response | up to approximately 8 months |
| Maximum serum concentration (Cmax) of AMG 701 | up to approximately 8 months |
| Progression-free survival (PFS) | up to approximately 3 years |
| Overall survival (OS) | up to approximately 3 years |
| Duration of response (DOR) | up to approximately 8 months |
| Time to maximum concentration (Tmax) of AMG 701 | up to approximately 8 months |
| Area under the concentration-time curve (AUC) of AMG 701 | up to approximately 8 months |
| Minimum concentration over the dosing interval (Ctrough) of AMG 701 | up to approximately 8 months |
| Incidence of anti-AMG 701 antibody formation | up to approximately 9 months |
| Overall response (OR) | up to approximately 8 months |
Outcome results
None listed