Study Evaluating AMG 424 in Subjects With Multiple Myeloma

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Relapsed/ Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: AMG 424


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 424<br>Comparison of different dosages of AMG 424 | Drug: AMG 424<br>* Subjects will receive IV infusions of AMG 424<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/ Refractory Multiple Myeloma, Multiple Myeloma, Oncology/Hematology, Immunotherapy