Study Evaluating AMG 424 in Subjects With Multiple Myeloma

A Phase 1, First-in-Human, Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 424 in Subjects With Multiple Myeloma

A multi-center Phase 1, First-in-Human study conducted in 2 Parts, testing AMG 424 in subjects with relapsed/ refractory multiple myeloma.

Study Overview

• Status: Terminated
• Conditions: Relapsed/ Refractory Multiple Myeloma
• Intervention / Treatment: Drug: AMG 424

Detailed Description

Part 1 of the study is dose evaluating and aimed at assessing the safety and tolerability of AMG 424 while determining the maximum tolerated dose (MTD) and/or biologically active dose in subjects with relapsed/ refractory multiple myeloma.

Part 2 of the study will further evaluate safety and tolerability of the AMG 424 MTD dose determined in Part 1, in groups of subjects with relapsed/ refractory multiple myeloma that include those with high or low cytogenetic risk.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Research Site
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Research Site
• United States
  • California
    • San Francisco, California, United States, 94143
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
    • Winston-Salem, North Carolina, United States, 27157
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Multiple myeloma meeting the following criteria:

• Pathologically-documented diagnosis of multiple myeloma that has relapsed after at least two prior lines of therapy that must include a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and, where approved and available, anti-CD38 therapy in any order OR that is refractory to PI, IMiD, and anti-CD38 therapy.

  ◾Subjects who could not tolerate a PI, IMiDs, or a CD38-directed therapeutic antibody due to unacceptable toxicities are eligible to enroll in the study.

• Measurable disease as per IMWG response criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

Exclusion Criteria:

• Known central nervous system involvement by multiple myeloma

• Previously received allogeneic stem cell transplant and one or more of the following:

  • received the transplant < 6 months prior to study Day 1
  • received immunosuppressive therapy < 3 months prior to study Day 1
  • any active acute graft versus host disease (GvHD), grade 2- 4, according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment
  • any systemic therapy against GvHD < 2 weeks prior to study Day 1
• 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)
• Evidence of primary or secondary plasma cell leukemia at the time of screening
• Waldenstrom's macroglobulinemia
• Amyloidosis
• Dexamethasone at cumulative doses of greater than 160 mg or equivalent <3 weeks prior to study Day 1 is not allowed. Use of topical or inhaled steroids is acceptable
• Anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) < 2 weeks prior to study Day 1
• Treatment with a therapeutic antibody targeting CD38 < 12 weeks prior to study Day 1
• Systemic radiation therapy or major surgery < 28 days prior to study Day 1 as well as focal radiotherapy < 14 days prior to study Day 1.
• Major surgery within 28 days prior to study Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG 424; Comparison of different dosages of AMG 424	Drug: AMG 424; Subjects will receive IV infusions of AMG 424

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject incidence of treatment emergent and treatment related adverse events as assessed by CTCAE version 4.0	Measure of Safety	12 Months
Subject incidence of dose limiting toxicities (DLTs)	Measure of Safety	28 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor activity	Efficacy parameter measured by IMWG response criteria	48 Months
Duration of Response	Measure of Response	48 Months
Maximum concentration (Cmax) of AMG 424	Characterize the pharmacokinetic (PK) profile following treatment with AMG 424	12 Weeks
Minimum concentration (Cmin) of AMG 424	Characterize the pharmacokinetic (PK) profile following treatment with AMG 424	12 Weeks
Time of maximum concentration (Tmax) of AMG 424	Characterize the pharmacokinetic (PK) profile following treatment with AMG 424	12 Weeks
Area under the concentration-time curve (AUC) of AMG 424	Characterize the pharmacokinetic (PK) profile following treatment with AMG 424	12 Weeks
Time to progression	Measure of Response	48 Months
Progression-Free Survival	Measure of Response	48 Months
Overall Survival	Measure of Response	48 Months

Collaborators and Investigators

• Sponsor: Xencor, Inc.

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2018
• Primary Completion (Actual): June 19, 2020
• Study Completion (Actual): June 19, 2020

Study Registration Dates

• First Submitted: February 1, 2018
• First Submitted That Met QC Criteria: February 20, 2018
• First Posted (Actual): February 26, 2018

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Immunotherapy; Oncology/Hematology; Relapsed/ Refractory Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 20160445

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No