Clinical trial NCT03411915: A Study of XmAb®18087 in Subjects With NET and GIST
Official title: A Phase 1 Multiple Dose Study to Evaluate the Safety and Tolerability of XmAb®18087 in Subjects With Advanced Neuroendocrine and Gastrointestinal Stromal Tumors (DUET-1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neuroendocrine Tumor
Gastrointestinal Neoplasm
Keywords: NET
GIST
DUET-1
Lead sponsor: Xencor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ICON plc
First posted: 2018-01-26
Enrollment: 62
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, multiple dose, ascending dose escalation study; to define a MTD/RD and regimen consisting of a first "priming" dose and escalated subsequent doses of XmAb18087; to describe safety and tolerability; to assess PK and immunogenicity; and to preliminarily assess anti-tumor activity of XmAb18087 in subjects with advanced NET or GIST.

The study will enroll dosing cohorts to establish a MTD/RD and regimen in subjects with advanced NET or GIST, then enroll additional subjects into separate NET and GIST expansion cohorts to collect additional data on safety and potential efficacy of XmAb18087.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed well differentiated low or intermediate grade (World Health Organization \[WHO\] Grade 1 or 2) NET of pancreatic, gastrointestinal, lung, or undetermined origin that is locally advanced or metastatic and has progressed within the past 12 months
* Histologically confirmed GIST that is locally advanced or metastatic
* NET and GIST tumors must be unresectable
* NET subjects must have progressed on or been ineligible for treatment with somatostatin analogues (SSA) and at least one other FDA-approved targeted therapy (everolimus or sunitinib).
* GIST subjects must have previously received all FDA-approved therapies (imatinib mesylate, sunitinib malate, and regorafenib) for which they are eligible
* Must have disease measurable by RECIST 1.1 criteria using either computed tomography (CT) or magnetic resonance imaging (MRI) scan
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

* Diagnosis of high-grade (WHO Grade 3) or poorly differentiated NET; high-grade neuroendocrine carcinoma; large cell neuroendocrine carcinoma, small cell carcinoma, or mixed small and large cell carcinoma.
* Subjects currently receiving anti-cancer therapies (other than SSAs, which may continue).
* Subjects who have received anti-cancer therapies within 2 weeks of the start of study drug (including chemotherapy, radiation therapy, immunotherapy, etc.).
* Must not be experiencing a Grade 3 or 4 toxicity from previous anti-cancer treatment
* Must not be receiving other anti-cancer therapies (except somatostatin analogues, which may be allowed)
* Must not have poorly controlled diabetes mellitus, known central nervous system involvement by malignant disease or insufficient bone marrow, renal, or hepatic function

Primary outcomes:
measure: Determine the safety and tolerability profile of XmAb18087
timeFrame: 84 Days
measure: Identify the maximum tolerated dose (MTD) and/or recommended dose (RD) and schedule of XmAb18087
timeFrame: 84 Days
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado, Anschutz Medical Campus
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medicine
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: James Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania, Abramson Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Senior Medical Director, Clinical Development, Xencor
name: Zequn Tang, MD, PhD
role: STUDY_DIRECTOR
References: