Study Evaluating AMG 424 in Subjects With Multiple Myeloma

Phase 1

Terminated

• Conditions: Relapsed/ Refractory Multiple Myeloma
• Interventions: Drug: AMG 424

• Registration Number: NCT03445663
• Lead Sponsor: Xencor, Inc.

Brief Summary

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

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 Timeline

• Study First Submitted: 2018-02-01
• Study First Submitted QC: 2018-02-20
• Study First Posted: 2018-02-26
• Study Start: 2018-07-31
• Primary Completion: 2020-06-19
• Study Completion: 2020-06-19
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-03
• Last Update Posted: 2023-03-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 27

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AMG 424	AMG 424	Comparison of different dosages of AMG 424

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Research Site; 🇦🇺 Fitzroy, Victoria, Australia