Clinical trial NCT03445663: Study Evaluating AMG 424 in Subjects With Multiple Myeloma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Relapsed/ Refractory Multiple Myeloma
Keywords: Relapsed/ Refractory Multiple Myeloma
Multiple Myeloma
Oncology/Hematology
Immunotherapy
Lead sponsor: Xencor, Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-26
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Subject incidence of treatment emergent and treatment related adverse events as assessed by CTCAE version 4.0
timeFrame: 12 Months
measure: Subject incidence of dose limiting toxicities (DLTs)
timeFrame: 28 Days
Secondary outcomes:
measure: Anti-tumor activity
timeFrame: 48 Months
measure: Duration of Response
timeFrame: 48 Months
measure: Maximum concentration (Cmax) of AMG 424
timeFrame: 12 Weeks
measure: Minimum concentration (Cmin) of AMG 424
timeFrame: 12 Weeks
measure: Time of maximum concentration (Tmax) of AMG 424
timeFrame: 12 Weeks
measure: Area under the concentration-time curve (AUC) of AMG 424
timeFrame: 12 Weeks
measure: Time to progression
timeFrame: 48 Months
measure: Progression-Free Survival
timeFrame: 48 Months
measure: Overall Survival
timeFrame: 48 Months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Research Site
state: California
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Fitzroy
country: Australia
facility: Research Site
state: Victoria
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: