An open label phase II study to find out if the drug PDR001 is safe and has beneficial effects in patient who have advanced or metastatic nonfunctionalneuroendocrine tumors of pancreatic, gastrointestinal, thoracic origins or poorly-differentiated gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) and have progressed on prior treatment

Phase 1

• Conditions: Advanced neuroendocrine tumor (NET) of pancreatic, GI or lung origin; MedDRA version: 21.0Level: PTClassification code 10052399Term: Neuroendocrine tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002522-36-IT
• Lead Sponsor: OVARTIS PHARMA AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2020-05-13
• Study Start: 2021-06-17
• Last Update Posted: 24 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 116

Inclusion Criteria

Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Written informed consent must be obtained prior to any screening procedures
2. Adult males or females = 18 years at screening.
3. Pathologically confirmed, advanced (unresectable or metastatic):
- Well-differentiated (G1 or G2) based on local pathology report, , non-functional
neuroendocrine tumor of GI, pancreatic or thoracic (including lung and thymus) origin.
- Poorly-differentiated GEP-NEC based on local pathology report
4. No active symptoms related to carcinoid syndrome during the last 3 months prior to start of study treatment.
5. Patients must have received prior treatment for advanced disease:
- Well-differentiated NET group:
a. Thoracic (lung and thymus origin) cohort:
- Thymus origin: at least one prior systemic therapy according to investigator’s choice
- Lung origin: at least one prior systemic therapy is required, which must include everolimus.
b. GI cohort: at least two prior systemic regimens, which must include everolimus. Prior systemic therapies may include: somatostatin analogs, PRRT, and/or chemotherapy.
c. pNET cohort: at least two prior systemic regimens, which must include everolimus and/or sunitinib. Prior systemic therapies may include: somatostatin analogs, PRRT and/or chemotherapy.
Note: For well-differentiated NET, Prior treatment with interferon alpha is allowed provided that it is not the last treatment received prior to study entry.
- Poorly-differentiated GEP-NEC group: at least one prior chemotherapy regimen according to Investigator’s choice.
6. Radiological documentation of disease progression:
- Well-differentiated NET group: Disease progression while on/or after the last treatment, and this progression must have been observed within 6 months prior to start of study treatment (i.e. maximum of 24 weeks from documentation of progression until study entry). Disease must show evidence of radiological disease progression based on scans performed not more than 12 months apart.
- Poorly-differentiated GEP-NEC group: Disease progression while on or after prior treatment.
7. At least one measurable lesion assessed by CT and/or MRI according to RECIST 1.1.
Note: Any lesions which have been subjected to percutaneous therapies or radiotherapy should not be considered measurable, unless the lesion has clearly progressed since the procedure.
8. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
9. Tumor biopsy material must be provided for all patients for the purpose of biomarker analysis:
- Well-differentiated (G1/2) NET: Biopsy material must be provided following the diagnosis of metastatic disease. The tumor sample must be collected from a metastatic site not previously irradiated and should preferably be taken within 6 months but not more than 24 months prior to start of study treatment.
- Poorly-differentiated GEP-NEC: Biopsy material must be collected from the primary tumor or from a metastatic site not previously irradiated, taken not more than 24 months prior to start of study treatment.
10. Women of childbearing potential must have had a negative serum pregnancy test within 72 hours prior to the start of study treatment. Highly effective contraception must be used while on study.
11. Patient is deemed by the investigator to have the ability and means to be compliant with the protocol (treatment and follow-up).
12. Patient must meet the following laboratory values at the screen

Exclusion Criteria

1. Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell
carcinoma.
2. Pretreatwith interferon as last treatment prior to start of study treatment
3. Prior treatment for study indication
4. Systemic chronic steroid therapy (= 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date for first dose of study treatment.
5. Any untreated central nervous system (CNS) lesion.
6. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents = 2 weeks prior to the first dose of study treatment.
7. Malignant disease, other than that being treated in this study.
8. Major surgery, open biopsy, or significant traumatic injury within 2 weeks prior to start of
study treatment.
9. Anticipation of the need for major surgical procedure during the course of the study
10. Radiation therapy within 4 weeks prior to start of study treatment
11. Hepatic intra-arterial embolization within the last 6 months.
12. History of severe hypersensitivity reactions to other monoclonal antibodies
13. Impaired cardiac function or clinically significant cardiac disease, including any of the
following:
14. Active, known or suspected autoimmune disease or a documented history of autoimmune
disease, including ulcerative colitis and Crohn's disease
15. Active infection requiring systemic antibiotic therapy.
16. Known history of testing positive for Human Immunodeficiency Virus (HIV) infection.
17. Patients with active Hepatitis B infection (HBsAg positive) will be excluded.
18. Patients with positive test for hepatitis C ribonucleic acid (HCV RNA)..
19. Any medical condition that would, in the investigator's judgment, prevent the patient's
participation in the clinical study due to safety concerns, compliance with clinical study
procedures or interpretation of study results.
20. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
21. Presence of = CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy, and ototoxicity, which are exclusion criteria if = CTCAE grade 3) due to prior cancer therapy.
22. Not able to understand and to comply with study instructions and requirements.
23. Pregnant or nursing (lactating) women confirmed by a positive hCG laboratory test within
72 hours prior to initiating study treatment. Note: Low levels of hCG may also be considered a tumor marker, therefore if low hCG levels are detected, another blood sample at least 4 days later must be taken to assess the kinetics of the increase and transvaginal ultrasound must be performed to rule out pregnancy.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified