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
Overview
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Xencor, Inc.
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Subject incidence of treatment emergent and treatment related adverse events as assessed by CTCAE version 4.0
Overview
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
AMG 424
Comparison of different dosages of AMG 424
Intervention: AMG 424 (Drug)
Outcomes
Primary Outcomes
Subject incidence of treatment emergent and treatment related adverse events as assessed by CTCAE version 4.0
Time Frame: 12 Months
Measure of Safety
Subject incidence of dose limiting toxicities (DLTs)
Time Frame: 28 Days
Measure of Safety
Secondary Outcomes
- Anti-tumor activity(48 Months)
- Duration of Response(48 Months)
- Maximum concentration (Cmax) of AMG 424(12 Weeks)
- Minimum concentration (Cmin) of AMG 424(12 Weeks)
- Time of maximum concentration (Tmax) of AMG 424(12 Weeks)
- Area under the concentration-time curve (AUC) of AMG 424(12 Weeks)
- Overall Survival(48 Months)
- Time to progression(48 Months)
- Progression-Free Survival(48 Months)