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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Neuroendocrine Tumor, Gastrointestinal Neoplasm

Intervention / Treatment
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* Biological: XmAb18087


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NET, GIST, DUET-1