Clinical trial NCT02955069: 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)
Official title: An Open Label Phase II Study to Evaluate 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 Have Progressed on Prior Treatment.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Well-differentiated Non-functional NET of Thoracic Origin
Well-differentiated Non-functional NET of Gastrointestinal Origin
Well-differentiated Non-functional NET of Pancreatic Origin
Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma
Keywords: Advanced or metastatic
NET
pNET
GI NET
thoracic NET
GEP-NEC
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-11-04
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC).
timeFrame: From baseline up to approximately 1.5 years
Secondary outcomes:
measure: Duration of Response (DOR) by RECIST 1.1 and as Per BIRC
timeFrame: From the date of first documented response (CR or PR) until the first documented disease progression or death, whichever comes first, assessed up to approximately 1.5 years
measure: Disease Control Rate by RECIST 1.1 and as Per BIRC
timeFrame: From baseline up to approximately 1.5 years
measure: Time to Response (TTR) by RECIST 1.1 and as Per BIRC
timeFrame: From baseline to the first documented response, assessed up to approximately 1.5 years
measure: Progression-free Survival (PFS) by RECIST 1.1 and as Per BIRC
timeFrame: From baseline until the date of the first documented radiological progression or death due to any cause, whichever comes first, assessed up to approximately 1.5 years
measure: Immune Related Overall Response Rate (irORR) by irRECIST and as Per BIRC
timeFrame: From baseline up to approximately 1.5 years
measure: Immune Related Duration of Response (irDoR) by irRECIST and as Per BIRC.
timeFrame: From the date of first documented confirmed response (irCR or irPR) until the first documented progression, assessed up to approximately 1.5 years
measure: Immune Related Time to Response (irTTR) by irRECIST and as Per BIRC
timeFrame: From baseline to the first documented response, assessed up to approximately 1.5 years
measure: Immune Related Disease Control Rate (irDCR) by irRECIST and as Per BIRC
timeFrame: From baseline up to approximately 1.5 years
measure: Immune Related Progression Free Survival (irPFS) by irRECIST and as Per BIRC
timeFrame: From baseline until the date of the first documented immune related progression or death due to any cause, whichever comes first, assessed up to approximately 1.5 years
measure: Overall Survival (OS)
timeFrame: From baseline until death due to any cause, assessed up to approx. 3 years
measure: Changes From Baseline in Chromogranin A (CgA) Levels
timeFrame: Baseline, day 1 of each cycle from Cycle 2 to end of treatment, assessed up to approx. 1.5 years. Cycle=28 days.
measure: Change From Baseline in Neuron Specific Enolase (NSE) Levels
timeFrame: Baseline, day 1 of each cycle from Cycle 2 to end of treatment, assessed up to approx. 1.5 years. Cycle= 28days
measure: PDR001 Plasma Concentration
timeFrame: Cycle(C)1 Day(D)1 pre-dose and 30min post-infusion,C2D1 Pre-dose,C3D1 Pre-dose and 30min post-infusion,D1 pre-dose from C4 to C13, assessed up to approx. 1.5 years.Cycle=28 days
measure: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life Score
timeFrame: Baseline, every 8 weeks from Cycle 3 Day 1 for the first 13 cycles and every 12 weeks from Cycle 13 Day 1 thereafter and end of treatment, assessed up to approx. 1.5 years. Cycle=28 days
measure: Change From Baseline in EQ-5D-5L Index Score
timeFrame: Baseline, every 8 weeks from Cycle 3 Day 1 for the first 13 cycles and every 12 weeks from Cycle 13 Day 1 thereafter, and end of treatment, assessed up to approx.1.5 year. Cycle=28 days
measure: PDR001 Anti-drug Antibodies (ADA) Prevalence at Baseline
timeFrame: Baseline
measure: PDR001 ADA Incidence On-treatment
timeFrame: Cycle(C)1 Day(D)1 pre-dose and 30min post-infusion,C2D1 Pre-dose,C3D1 Pre-dose and 30min post-infusion,D1 pre-dose from C4 to C13 and every 6 cycles until C25, and end of treatment, assessed up to approx. 1.5 years. Cycle=28 days
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers SC-2
state: Colorado
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: University of TX MD Anderson Cancer Center
state: Texas
city: St Leonards
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Brussels
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Lyon
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 4
country: France
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Meldola
country: Italy
facility: Novartis Investigative Site
state: FC
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: