Relapsed/ Refractory Multiple Myeloma
Conditions
Keywords
Relapsed/ Refractory Multiple Myeloma, Multiple Myeloma, Oncology/Hematology, Immunotherapy
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.
Interventions
DRUGAMG 424
Subjects will receive IV infusions of AMG 424
Sponsors
Xencor, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Anti-tumor activity | 48 Months | Efficacy parameter measured by IMWG response criteria |
| Time to progression | 48 Months | Measure of Response |
| Progression-Free Survival | 48 Months | Measure of Response |
| 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 |
| Duration of Response | 48 Months | Measure of Response |
Countries
Australia, United States
Outcome results
None listed