A Phase 1b Open-label Study Evaluating the Safety and Pharmacokinetics of Subcutaneous AMG 701 for the Treatment of Relapsed or Refractory Multiple Myeloma (ProxiMMity-1)
A Phase 1b Open-label Study Evaluating the Safety and Pharmacokinetics of Subcutaneous AMG 701 for the Treatment of Relapsed or Refractory Multiple Myeloma (ProxiMMity-1)
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)
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 :
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:
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
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)
Left ventricular ejection fraction ≥ 50% as assessed by transthoracic echocardiogram (TTE) or multigated acquisition (MUGA) scan.
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:
History of malignancy other than multiple myeloma within the past 3 years with the following exceptions:
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:
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 exclusion criteria and there is agreement to allow by both the investigator and Amgen medical monitor.
Known hypersensitivity to immunoglobulins.
Current autoimmune disease that is not well-controlled.
Past history or current significant inflammatory neuropathy such as Guillain-Barré syndrome, Chronic inflammatory demyelinating polyradiculoneuropathy, or Multifocal motor neuropathy.
Previously received an allogeneic stem cell transplant and the occurrence of 1 or more of the following:
Autologous stem cell transplantation less than 90 days prior to study day 1.
Last non-antibody anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) < 2 weeks and last anticancer therapeutic antibody < 4 weeks prior to study day 1.
Lymphodepleting chemotherapy (eg, fludarabine, cyclophosphamide, or anti-CD52 antibody in association with chimeric antigen-receptor T-cell therapy) < 3 months prior to study day 1.
Radiation therapy to multiple anatomic sites within 28 days prior to study day 1.
Focal radiotherapy within 14 days prior to study day 1.
Treatment with systemic immune modulators including, but not limited to, non-topical systemic corticosteroids (unless the dose is less ≤ 10 mg/day prednisone or equivalent), cyclosporine, and tacrolimus within 2 weeks before study day 1.
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.
Administration of bone preserving therapies (including bisphosphonates) within 14 days of cycle 1 day 1.
Major surgery defined as surgery requiring general anesthesia with endotracheal intubation within 28 days prior to study day 1, unless discussed with and eligibility approved by Amgen medical monitor.
Female participants of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 75 days after the last dose of AMG 701.
Female participants who are breastfeeding or who plan to breastfeed while on study through 75 days after the last dose of AMG 701.
Female participants planning to become pregnant while on study through 75 days after the last dose of AMG 701.
Female participants with a positive pregnancy test.
Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 135 days after the last dose of AMG 701.
Male participants unwilling to abstain from donating sperm during treatment and for an additional 135 days after the last dose of AMG 701.
Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the participant and investigator's knowledge.
History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.