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Clinical Trial 19577

Cancer Type:
Interventions:XmAb18087

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Jonathan Strosberg

Call 813-745-6100
or 1-800-679-0775
Overview

Study 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)

Summary

The primary purposes of this research study are to: determine the safety and tolerability of the investigational drug, XmAb18087; if the XmAb18087 works in treating these types of tumors; if participants have side effects from XmAb18087 and to find the best dose for treating their type of tumor. XmAb18087 is an investigational drug that is designed to activate the participant's own cells to kill their tumor.

Objective

Primary Objectives: 1. To determine the safety and tolerability profile of XmAb18087 in subjects with advanced well-differentiated neuroendocrine tumors (NET) of pancreatic, gastrointestinal, lung, and undetermined origin, and subjects with advanced gastrointestinal stromal tumors (GIST). 2. To identify the maximum tolerated dose (MTD) and/or recommended dose (RD) and schedule of XmAb18087 administered by intravenous (IV) dosing on days 1, 8, 15, and 22 of each 28-day cycle in subjects with advanced NET or advanced GIST. Secondary Objectives: 1. To characterize the pharmacokinetics (PK) and immunogenicity of XmAb18087. 2. To preliminarily assess anti-tumor activity of XmAb18087 by overall response rates (ORR) and progression-free survival (PFS) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria, as well as duration of response. Exploratory Objectives: 1. To assess the incidence, timing, and severity of cytokine release syndrome (CRS) by following: a. CRS-related adverse events (AEs; incidence and grade of AEs and incidence of serious AEs ; [SAEs]); b. Biomarkers of CRS. 2. To assess the effect of XmAb18087 administration on subject fasting blood glucose values. 3. To measure changes in peripheral blood lymphocyte subsets and in T-cell activation/exhaustion after XmAb18087 administration by flow cytometry. 4. To characterize pharmacodynamics (PD) in NET subjects by correlation of response with serum Chromogranin A levels, Octreoscan® values, and NETestTM results after XmAb18087administration. 5. To evaluate by immunohistochemistry, when possible, tumor cell expression of somatostatin receptor (SSTR) 2 and programmed cell death ligand-1 (PD-L1), and tumor infiltrating immune cell expression of programmed cell death protein-1 (PD-1)/PD-L1 after XmAb18087 administration.

Inclusion Criteria

  • Histologically or cytologically confirmed well differentiated low or intermediate grade (World Health Organization [WHO] Grade 1 or 2) neuroendocrine tumor (NET) of pancreatic, gastrointestinal, lung, or undetermined origin that is locally advanced or metastatic and has progressed within the past 12 months
  • Histologically confirmed gastrointestinal stomal tumor (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 participants must have previously received all FDA-approved therapies (imatinib mesylate, sunitinib malate, and regorafenib) for which they are eligible
  • Must have disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 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.
  • Currently receiving anti-cancer therapies (other than SSAs, which may continue).
  • Have received anti-cancer therapies within 2 weeks of the start of study drug (including chemotherapy, radiation therapy, immunotherapy, etc.).
  • Experiencing a Grade 3 or 4 toxicity from previous anti-cancer treatment
  • Receiving other anti-cancer therapies (except somatostatin analogues, which may be allowed)
  • Have poorly controlled diabetes mellitus, known central nervous system involvement by malignant disease or insufficient bone marrow, renal, or hepatic function