Pembrolizumab and Lanreotide Acetate in Treating Patients with Gastroenteropancreatic Neuroendocrine Tumors That Are Recurrent, Metastatic, or Cannot Be Removed by Surgery
This phase Ib / II trial studies how well pembrolizumab and lanreotide acetate work in treating patients with gastroenteropancreatic neuroendocrine tumors that have come back, have spread to other places in the body, or cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Lanreotide acetate may prevent signals that help cancer cells survive and grow. Giving pembrolizumab and lanreotide may work better in treating patients with gastroenteropancreatic neuroendocrine tumors.
- Willing and able to provide written informed consent for the trial
- 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)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Absolute neutrophil count (ANC) >= 1,500 /mcL
- Platelets >= 100,000 /mcL
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
- Serum creatinine =< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance (CrCL) per institutional standard (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN
- Serum total bilirubin =< 1.5 x ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [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
- Tumor mitotic rate > 20/10 high-power field (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 carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- 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 stability
- 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
- Known history of, or any evidence of active, non-infectious pneumonitis
- Active infection requiring systemic therapy
- 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
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- 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
- Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- 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 not allowed
- History of intolerance to somatostatin analogues
Locations & Contacts
Contact: Michael A. Morse
Trial Objectives and Outline
I. To evaluate the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 to pembrolizumab in combination with lanreotide acetate (lanreotide depot) in subjects with progressive, advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
I. To assess the safety of pembrolizumab in combination with lanreotide depot in subjects with GEP-NETs.
II. To assess progression free survival (PFS) of pembrolizumab in combination with lanreotide depot in subjects with GEP-NETs.
III. To assess the overall survival (OS) of pembrolizumab in combination with lanreotide depot in subjects with GEP-NETs.
IV. To evaluate the ORR by Immune-Related Response Criteria (irRC) to pembrolizumab in combination with lanreotide depot in subjects with progressive, advanced or metastatic GEP-NETs.
I. To characterize changes in circulating immune cells in subjects with GEP-NETs treated with pembrolizumab in combination with lanreotide depot.
II. To determine whether safety and efficacy parameters (ORR, PFS, OS) correlate with PD-L1 expression within the tumor in pre-treatment specimens.
III. To explore the correlation between blood-based biomarkers and clinical outcomes.
Patients receive pembrolizumab intravenously (IV) over 30 minutes and lanreotide acetate subcutaneously (SC) on day 1. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then periodically for up to 48 weeks.
Trial Phase & Type
Duke University Medical Center
Michael A. Morse
Secondary IDs NCI-2017-00979
Clinicaltrials.gov ID NCT03043664