Clinical Trials

Inclusion Criteria:

• Able to provide written informed consent.
• Adult and adolescent (age ≥ 12 years) subjects.
• Diagnosis of either:
  • Histologically or cytologically confirmed well-differentiated low or intermediate-grade (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.
    • Note: 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 targeted therapy. SSA therapy may continue if the subject has been on a stable dose for at least 3 months.
• GIST subjects must have previously received all FDA-approved therapies (imatinib mesylate, sunitinib malate, and regorafenib) for which they are eligible.
• Subjects must have disease measurable by RECIST 1.1 criteria using either CT or magnetic resonance imaging (MRI) scan.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Female subjects of childbearing potential must agree to use a highly effective method of birth control during and for 4 weeks after completion of study.
• Women are considered to be of childbearing potential unless it is documented that they are:
  • over the age of 60; or
  • postmenopausal by history with no menses for 1 year and confirmed by FSH (using local reference ranges); or
  • have a history of hysterectomy and/or bilateral oophorectomy; or have a history of bilateral tubal ligation. Highly effective methods of birth control include hormonal birth control (oral, intravaginal, transdermal, implantable, or intrauterine), intrauterine devices (IUDs), vasectomy, or any double-barrier methods (combination of male condom and spermicide with cap, diaphragm, or sponge).
• Able and willing to complete the entire study according to the study schedule.

Exclusion Criteria:

• Diagnosis of high-grade (WHO Grade 3) or poorly differentiated NET; high-grade neuroendocrine carcinoma; adenocarcinoid or goblet cell carcinoid tumor; and 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.).
• Failure to recover from Grade 3 or 4 toxicity from previous anti-cancer treatment.
• Known central nervous system involvement by malignant disease.
• Platelet count < 50 × 10^9 /L.
• Absolute neutrophil count < 1.0 x 10^9/L.
• Aspartate aminotransferase (AST) ≥ 3 × upper limit of normal (ULN), or if subject has known liver metastases, AST ≥ 7 × ULN.
• Alanine aminotransferase (ALT) ≥ 3 × ULN, or if subject has known liver metastases, ALT ≥ 7 × ULN.
• Estimated creatinine clearance < 50 mL/min calculated by the Cockroft Gault or Modification of Diet in Renal Disease formulas at screening.
• Poorly controlled diabetes mellitus as evidenced by an HbA1c level ≥ 10%, or significant diabetes-related dietary or therapeutic regimen changes within 12 weeks of enrollment.
• Active heart failure of New York Heart Association (NYHA) Functional Capacity Class III or IV.
• Active autoimmune disease.
• History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic or psychiatric) other than their primary malignancy that in the opinion of the Investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
• Treatment for any serious bacterial, viral, parasitic, or systemic fungal infections within the 30 days prior to study entry.
• Positive test for HIV or hepatitis C antibodies.
• Positive test for HBsAg or HBcAb (a subject whose HBsAg is negative and HBcAb is positive may be enrolled if an HBV DNA test is negative and either the subject is treated with potent anti-viral therapy or is re-tested for HBsAg and HBV DNA every month).
• Subject is pregnant or breastfeeding, or planning to become pregnant while enrolled in the study, up to the EOS visit.
• Positive serum pregnancy test (i.e., urine human chorionic gonadotropin) at screening.