Study of Efficacy and Safety of PDR001 in Patients With Advanced or Metastatic, Well-differentiated, Non-functional Neuroendocrine Tumors of Pancreatic, Gastrointestinal (GI), or Thoracic Origin or Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC)

Novartis

Status and phase: Completed; Phase 2

Conditions: Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma; Well-differentiated Non-functional NET of Pancreatic Origin; Well-differentiated Non-functional NET of Gastrointestinal Origin; Well-differentiated Non-functional NET of Thoracic Origin

Treatments: Drug: PDR001

Study type: Interventional

Funder types: Industry

Identifiers

NCT02955069

CPDR001E2201

2016-002522-36 (EudraCT Number)

Details and patient eligibility

About

This study aimed to investigate the efficacy and safety of PDR001 in patients with advanced or metastatic, well-differentiated, non-functional neuroendocrine tumors of pancreatic, gastrointestinal (GI), or thoracic origin or poorly-differentiated gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) that progressed on prior treatment.

Full description

Two groups of adult patients with advanced (unresectable or metastatic) were included in this study:

• Well-differentiated (G1/2), non-functional, neuroendocrine tumor of GI, pancreatic or thoracic (lung/thymus) origin who have progressed on prior treatment
• Poorly-differentiated GEP-NEC who have progressed on or after one prior chemotherapy regimen.

The study was comprised of the following periods: screening, treatment, end of treatment (EOT), safety follow-up (30-Days, 60-Days, 90-Days, 120-Days, and 150-Days after the last dose of PDR001) and post-treatment efficacy follow-up. Subjects were treated with PDR001 as an infusion at a flat dose of 400 mg every 4 weeks (Q4W). Subjects were to continue study treatment beyond disease progression by RECIST 1.1 until disease progression as per irRECIST, as per BIRC, unacceptable toxicity, start of new antineoplastic therapy, withdrawal of consent, physician's decision, lost to follow-up, death, or study termination by the Sponsor.

Enrollment: 116 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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
• No active symptoms related to carcinoid syndrome during the last 3 months prior to start of study treatment.
• Patients must have been pretreated for advanced disease - the number of prior systemic therapy/regimen depended on which origin for NET and for GEP-NEC
• Tumor biopsy material must be provided for all patients for the purpose of biomarker analysis
• 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.

Exclusion criteria

• Well-differentiated grade 3 neuroendocrine tumors; poorly-differentiated neuroendocrine carcinoma of any origin (other than GEP-NEC); including NEC of unknown origin, adenocarcinoid, and goblet cell carcinoid
• Pretreatment with interferon as last treatment prior to start of study treatment.
• Prior treatment for study indication with:
• Antibodies or immunotherapy within 6 weeks before the first dose of study treatment.
• Peptide Radionuclide Receptor Therapy (PRRT) administered within 6 months of the first dose.
• Systemic antineoplastic therapy
• Tyrosine kinase inhibitors within 14 days or 5 half-lives, whichever is longer, before the first dose of study treatment.
• Prior Programmed Death-1 (PD-1) or Programmed Death-Ligand 1 (PD-L1) directed therapy.
• Cryoablation, radiofrequency ablation, or trans-arterial embolization of hepatic metastases
• History of severe hypersensitivity reactions to other monoclonal antibodies which in the opinion of the investigator may pose an increased risk of a serious infusion reaction.

Other inclusion/exclusion criteria might apply

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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116 participants in 1 patient group

PDR001

Experimental group

Description:

Subjects with advanced or metastatic, well-differentiated, NET of pancreatic, GI, or thoracic origin or poorly-differentiated GEP-NEC, that have progressed on prior treatment were treated with 400mg PDR001 administered via intravenous infusion once every 4 weeks.

Treatment:

Drug: PDR001