A Study of XmAb®18087 in Subjects With NET and GIST

Sponsor

Xencor, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03411915

Collaborator

ICON plc (Industry)

Enrollment

Locations

Arm

45.1

Actual Duration (Months)

3.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Tumor Gastrointestinal Neoplasm	Biological: XmAb18087	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jan 22, 2018

Actual Primary Completion Date :

Oct 26, 2021

Actual Study Completion Date :

Oct 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: XmAb18087 XmAb18087 administered on days 1, 8, 15, and 22 of each 28-day cycle for a total of 3 cycles	Biological: XmAb18087 monoclonal bispecific antibody

Arm

Intervention/Treatment

Experimental: XmAb18087

XmAb18087 administered on days 1, 8, 15, and 22 of each 28-day cycle for a total of 3 cycles

Biological: XmAb18087

monoclonal bispecific antibody

Outcome Measures

Primary Outcome Measures

Determine the safety and tolerability profile of XmAb18087 [84 Days]
Treatment-related adverse events as assessed by CTCAE v4.03
Identify the maximum tolerated dose (MTD) and/or recommended dose (RD) and schedule of XmAb18087 [84 Days]
Establishing a safe and tolerable dose of XmAb18087 administered by intravenous (IV) dosing in NET and GIST patients

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Phoenix	Arizona	United States	85054
2	City of Hope Medical Center	Duarte	California	United States	91010
3	Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California	United States	90048
4	Stanford Cancer Center	Palo Alto	California	United States	94304
5	University of Colorado, Anschutz Medical Campus	Aurora	Colorado	United States	80045
6	Mayo Clinic	Jacksonville	Florida	United States	32224
7	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
8	Emory University	Atlanta	Georgia	United States	30322
9	Northwestern Medicine	Chicago	Illinois	United States	60611
10	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
11	Mayo Clinic	Rochester	Minnesota	United States	55905
12	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
13	James Cancer Center	Columbus	Ohio	United States	43210
14	University of Pennsylvania, Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
15	MD Anderson Cancer Center	Houston	Texas	United States	77030
16	University of Virginia	Charlottesville	Virginia	United States	22908