This study is for patients with non-resectable, recurrent, or metastatic well or moderately
differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
The study will be conducted in two stages: 1) Safety Run-In and 2) Expanded Cohort.
1. Safety run-in: The first stage will include a safety run-in of 6 patients treated with
pembrolizumab 200 mg intravenous (IV) every 3 weeks and lanreotide depot 90mg
subcutaneous (SQ) every 3 weeks. Up to 6 patients at the Duke Cancer Institute will be
accrued at the starting dose level. If one or less subject meets treatment-related
discontinuation criteria (as specified in the protocol) during Cycle 1, then the study
will proceed to the second stage, Expanded Cohort.
2. Expanded Cohort: Patients will be treated with pembrolizumab 200mg IV every 3 weeks and
lanreotide depot 90mg SQ every 3 weeks as determined by the Safety Run-In Cohort.
1. Willing and able to provide written informed consent for the trial.
2. At least 18 years of age on day of signing informed consent.
3. 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.)
4. 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.)
5. At least one measurable lesion based on RECIST version 1.1.
6. 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
7. ECOG performance status of 0 or 1 (refer to Appendix C).
8. 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
- Serum total bilirubin ≤ 1.5 X ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver
- Albumin ≥ 2.5 mg/dL
9. Negative serum pregnancy test within ≤ 7 days prior to the first dose of study drug,
for women of childbearing potential only.
10. 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.
11. 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.
1. Tumor mitotic rate >20/10 hpf and/or Ki67 index >20% (if available).
2. 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.
3. 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.
4. Known history of active TB (Bacillus Tuberculosis).
5. Hypersensitivity to pembrolizumab or lanreotide or any of their excipients.
6. 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.
7. 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
8. 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.
9. Known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.
10. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Subjects with previously treated brain metastases may participate provided they are
stable (without evidence of progression by imaging for at least four weeks prior to
the first dose of trial treatment and any neurologic symptoms have returned to
baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to the first dose of study drug. This exception
does not include carcinomatous meningitis which is excluded regardless of clinical
11. Active autoimmune disease that has required systemic treatment in the past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
12. Known history of, or any evidence of active, non-infectious pneumonitis.
13. Active infection requiring systemic therapy.
14. History or current evidence of any condition, therapy, or laboratory abnormality that
might confound the results of the trial, interfere with the subject's participation
for the full duration of the trial, or is not in the best interest of the subject to
participate, in the opinion of the treating physician.
15. Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial.
16. Pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of study drug.
17. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
18. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
19. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
20. Live vaccine within 30 days of planned start of study drug regimen. Seasonal influenza
vaccines for injection are generally inactivated flu vaccines and are allowed; however
intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are
21. History of intolerance to somatostatin analogues.