Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors

Inclusion Criteria

• Willing and able to provide written informed consent for the trial.
• At least 18 years of age on day of signing informed consent.
• Non-resectable, recurrent, or metastatic well- or moderately-differentiated gastroenteropancreatic neuroendocrine tumor (GEP-NETs) with disease progression within the last 12 months. (Patients who have received prior local therapy, including but not limited to embolization, chemoembolization, radiofrequency ablation, radiation therapy, are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of > 20% in the size. Prior local therapy must be completed at least 4 weeks prior to the baseline scan.)
• Prior somatostatin analogue therapy. (Patients should receive the first dose of study drug no sooner than 4 weeks from the last dose of somatostatin analogue.)
• At least one measurable lesion based on RECIST version 1.1.
• Agrees to provide available archived tumor tissue specimen. (Patients who do not have available archived tumor must agree to have core or excisional biopsy of a tumor lesion obtained up to 42 days prior to the first dose of study drug, if safely accessible. If archived tissue is not available and the tumor is not amenable to safe biopsy, subject is still eligible to participate.)
• ECOG performance status of 0 or 1.
• Adequate organ function defined as:
• Absolute neutrophil count (ANC) ≥ 1, 500 /mcL
• Platelets ≥ 100,000 /mcL
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Serum creatinine OR calculated creatinine clearance (CrCL) per institutional standard (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 X upper limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
• Serum total bilirubin ≤ 1.5 X ULN
• AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Albumin ≥ 2.5 mg/dL
• Negative serum pregnancy test within ≤ 7 days prior to the first dose of study drug, for women of childbearing potential only.
• Female subjects agree to use two birth control methods, be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study drug.
• Male subjects agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.

Exclusion Criteria

• Tumor mitotic rate >20/10 hpf and/or Ki67 index >20% (if available).
• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to pembrolizumab or lanreotide or any of their excipients.
• Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Prior major surgery within 2 weeks prior to the first dose of study drug or who has not recovered adequately from the toxicity and/or complications from the intervention.
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcino