Phase 2
N=116
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)
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
Bottom Line
View on ClinicalTrials.gov: NCT02955069 ↗Enrolled (actual)
116
Serious AEs
30.2%
Results posted
Apr 2021
Primary outcome: Primary: Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC). — 7.4; 4.8 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- PDR001 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Aug 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC). |
7.4; 4.8 | — |
| SECONDARY Duration of Response (DOR) by RECIST 1.1 and as Per BIRC |
250; 270 | — |
| SECONDARY Disease Control Rate by RECIST 1.1 and as Per BIRC |
64.2; 19.0 | — |
| SECONDARY Time to Response (TTR) by RECIST 1.1 and as Per BIRC |
110; 53 | — |
| SECONDARY Progression-free Survival (PFS) by RECIST 1.1 and as Per BIRC |
3.8; 1.8 | — |
| SECONDARY Immune Related Overall Response Rate (irORR) by irRECIST and as Per BIRC |
7.4; 4.8 | — |
| SECONDARY Immune Related Duration of Response (irDoR) by irRECIST and as Per BIRC. |
228; 270 | — |
| SECONDARY Immune Related Time to Response (irTTR) by irRECIST and as Per BIRC |
110; 53 | — |
| SECONDARY Immune Related Disease Control Rate (irDCR) by irRECIST and as Per BIRC |
66.3; 19.0 | — |
| SECONDARY Immune Related Progression Free Survival (irPFS) by irRECIST and as Per BIRC |
3.8; 1.8 | — |
| SECONDARY Overall Survival (OS) |
23.4; 6.8 | — |
| SECONDARY Changes From Baseline in Chromogranin A (CgA) Levels |
874.6; 6466.9; -1811.7; 706.5; 579.9; 1544.5 | — |
| SECONDARY Change From Baseline in Neuron Specific Enolase (NSE) Levels |
0.8; 27.9; 2.5; 32.6; -0.1; 21.9 | — |
| SECONDARY PDR001 Plasma Concentration |
0; 0; 106; 100; 26.8; 25.8 | — |
| SECONDARY 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 |
-1.00; -11.11; -1.91; -4.17; 1.96; 25.00 | — |
| SECONDARY Change From Baseline in EQ-5D-5L Index Score |
0.03; -0.09; -0.02; 0.02; -0.04; 0.16 | — |
| SECONDARY PDR001 Anti-drug Antibodies (ADA) Prevalence at Baseline |
1; 0 | — |
| SECONDARY PDR001 ADA Incidence On-treatment |
10; 2 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT02955069). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.