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.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 116
- 试验地点
- 8
- 主要终点
- Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC).
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
PDR001
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.
干预措施: PDR001 (Drug)
结局指标
主要结局
Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC).
时间窗: From baseline up to approximately 1.5 years
ORR is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), according to BIRC radiological assessment by RECIST 1.1. CR: disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
次要结局
- Duration of Response (DOR) by RECIST 1.1 and as Per BIRC(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)
- Disease Control Rate by RECIST 1.1 and as Per BIRC(From baseline up to approximately 1.5 years)
- Immune Related Overall Response Rate (irORR) by irRECIST and as Per BIRC(From baseline up to approximately 1.5 years)
- Immune Related Duration of Response (irDoR) by irRECIST and as Per BIRC.(From the date of first documented confirmed response (irCR or irPR) until the first documented progression, assessed up to approximately 1.5 years)
- Time to Response (TTR) by RECIST 1.1 and as Per BIRC(From baseline to the first documented response, assessed up to approximately 1.5 years)
- Overall Survival (OS)(From baseline until death due to any cause, assessed up to approx. 3 years)
- Changes From Baseline in Chromogranin A (CgA) Levels(Baseline, day 1 of each cycle from Cycle 2 to end of treatment, assessed up to approx. 1.5 years. Cycle=28 days.)
- Change From Baseline in Neuron Specific Enolase (NSE) Levels(Baseline, day 1 of each cycle from Cycle 2 to end of treatment, assessed up to approx. 1.5 years. Cycle= 28days)
- PDR001 Plasma Concentration(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)
- Progression-free Survival (PFS) by RECIST 1.1 and as Per BIRC(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)
- Immune Related Time to Response (irTTR) by irRECIST and as Per BIRC(From baseline to the first documented response, assessed up to approximately 1.5 years)
- Immune Related Disease Control Rate (irDCR) by irRECIST and as Per BIRC(From baseline up to approximately 1.5 years)
- Immune Related Progression Free Survival (irPFS) by irRECIST and as Per BIRC(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)
- 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(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)
- Change From Baseline in EQ-5D-5L Index Score(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)
- PDR001 Anti-drug Antibodies (ADA) Prevalence at Baseline(Baseline)
- PDR001 ADA Incidence On-treatment(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)