Well-differentiated Non-functional NET of Thoracic OriginPhase 2NCT02955069
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)
A Phase 2 study testing PDR001 in people with Well-differentiated Non-functional NET of Thoracic Origin and Well-differentiated Non-functional NET of Gastrointestinal Origin, run by Novartis Pharmaceuticals at 35 sites in 12 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Well-differentiated Non-functional NET of Thoracic Origin, Well-differentiated Non-functional NET of Gastrointestinal Origin, Well-differentiated Non-functional NET of Pancreatic Origin
- What is being tested?
- PDR001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 35 sitesin 12 countries
- Study dates
- 14 Feb 2017to 13 May 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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 locations and contacts
35 sites in 12 countries.
35 sites in 12 countries
United States7 sites
Rocky Mountain Cancer Centers SC-2
Denver, Colorado, 80218
City of Hope National Medical Center
Duarte, California, 91010
University of TX MD Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
Montefiore Medical Center
The Bronx, New York, 10461
Italy6 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Meldola, FC, 47014
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20141
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Roma, RM, 00189
Germany4 sites
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Mainz, 55131
Novartis Investigative Site
Marburg, 35039
Japan4 sites
Novartis Investigative Site
Chuo Ku, Tokyo, 104 0045
Novartis Investigative Site
Fukuoka, Fukuoka, 812-8582
Novartis Investigative Site
Kashiwa, Chiba, 277 8577
Novartis Investigative Site
Nagoya, Aichi-ken, 464 8681
France3 sites
Novartis Investigative Site
Lyon, 69437
Novartis Investigative Site
Marseille, 13273
Novartis Investigative Site
Toulouse, 31054
Spain3 sites
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28041
Belgium2 sites
Novartis Investigative Site
Brussels, BE-B-1200
Novartis Investigative Site
Leuven, 3000
Canada2 sites
Novartis Investigative Site
Montreal, Quebec, H3T 1E2
Novartis Investigative Site
Toronto, Ontario, M4N 3M5
Australia1 site
Novartis Investigative Site
St Leonards, New South Wales, 2065
About this study
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.
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.
Read the 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.
- 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
- Being tested
- PDR001
- Keywords
- Advanced or metastatic, NET, pNET, GI NET, thoracic NET, GEP-NEC
- Medical subject headings
- Neoplasm Metastasis, Neuroectodermal Tumors, Primitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDR001Drug
Also called Spartalizumab
PDR001 was administered at a dose of 400 mg via intravenous infusion once every 4 weeks (Q4W). PDR001 was administered on Day 1 of every cycle. Each cycle was 28 days.
| Study group | Role | What they receive |
|---|---|---|
| PDR001 | Experimental | 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. Receives: Drug: PDR001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC).
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.
Measured: From baseline up to approximately 1.5 years
Secondary outcomes (17)
Duration of Response (DOR) by RECIST 1.1 and as Per BIRC
DOR is defined as the time between the date of first documented response (CR or PR) and the date of first documented disease progression by RECIST 1.1 and as per BIRC or death due to underlying cancer. For DOR analysis, participants continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment. An adequate tumour assessment is a tumour assessment with an overall response other than unknown.
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.
Measured: 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
Disease control rate is defined as the proportion of patients with best overall response of CR, PR or stable disease (SD) according to RECIST 1.1 criteria and as per BIRC.
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.
SD: neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Measured: From baseline up to approximately 1.5 years
Time to Response (TTR) by RECIST 1.1 and as Per BIRC
TTR is defined as the time from the date of start of treatment to the first documented response of either CR or PR, which must be subsequently confirmed. TTR was evaluated according to RECIST 1.1 and as per BIRC.
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.
Measured: From baseline to the first documented response, assessed up to approximately 1.5 years
Progression-free Survival (PFS) by RECIST 1.1 and as Per BIRC
PFS is defined as the time from the date of first dose to the date of the first documented radiological progression or death due to any cause. PFS was evaluated according to RECIST 1.1 and as per BIRC. For participants who had not progressed or died at the analysis cut-off date, PFS was censored at the date of the last adequate tumor evaluation date. An adequate tumour assessment is a tumour assessment with an overall response other than unknown.
Measured: 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 Overall Response Rate (irORR) by irRECIST and as Per BIRC
irORR is the proportion of patients with a best overall response of immune related Complete Response (irCR) or immune related partial response (irPR), according to BIRC assessment by irRECIST.
irCR: Complete disappearance of all measurable and non-measurable lesions. In addition, any pathological lymph nodes must have a reduction in short axis to < 10 mm.
irPR: At least 30% decrease in the total measurable tumor burden (TMTB) compared to baseline and not qualifying for irCR or immune related progressive disease (irPD).
Measured: From baseline up to approximately 1.5 years
Immune Related Duration of Response (irDoR) by irRECIST and as Per BIRC.
irDOR is defined as the time from first documentation of irCR or irPR until the time of first documentation of progression per irRECIST based on BIRC assessment. Participants continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment. An adequate tumour assessment is a tumour assessment with an overall response other than unknown for irRECIST.
irCR: Complete disappearance of all measurable and non-measurable lesions. In addition, any pathological lymph nodes must have a reduction in short axis to < 10 mm.
irPR: At least 30% decrease in the TMTB compared to baseline and not qualifying for irPD or irCR
Measured: From the date of first documented confirmed response (irCR or irPR) until the first documented progression, assessed up to approximately 1.5 years
Immune Related Time to Response (irTTR) by irRECIST and as Per BIRC
irTTR is defined as the time between date of start of treatment until first documented response (confirmed irCR or irPR) by irRECIST and as per BIRC.
irCR: Complete disappearance of all measurable and non-measurable lesions. In addition, any pathological lymph nodes must have a reduction in short axis to < 10 mm.
irPR: At least 30% decrease in the TMTB compared to baseline and not qualifying for irPD or irCR.
Measured: 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
irDCR is defined as the proportion of patients with a best overall response of irCR or irPR or immune related stable disease (irSD) according to irRECIST and as per BIRC.
irCR: Complete disappearance of all measurable and non-measurable lesions. In addition, any pathological lymph nodes must have a reduction in short axis to < 10 mm.
irPR: At least 30% decrease in the TMTB compared to baseline and not qualifying for irPD or irCR.
irSD: Neither a sufficient shrinkage to qualify for irPR or irCR, nor an increase in lesions, or a clear and unequivocal progression of existing nontarget or new non-measurable lesions that would qualify for irPD.
Measured: From baseline up to approximately 1.5 years
Immune Related Progression Free Survival (irPFS) by irRECIST and as Per BIRC
irPFS is defined as the time from date of start of treatment to the date of event defined as the first documented assessment of immune related progression that is confirmed or death due to any cause. If a patient has not had an event, immune related progression-free survival was censored at the date of last adequate tumor assessment. An adequate tumor assessment is a tumor assessment with overall response other than unknown for irRECIST.
Measured: 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
Overall Survival (OS)
OS is defined as the time from the start of treatment date to the date of death, due to any cause. If a patient was not known to have died, then OS was censored at the latest date the patient was known to be alive.
Measured: From baseline until death due to any cause, assessed up to approx. 3 years
Changes From Baseline in Chromogranin A (CgA) Levels
Blood samples were collected for assessment of CgA level. Change from Baseline at a particular visit was calculated as the CgA level at that visit minus Baseline.
Measured: 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
Blood samples were collected for assessment of NSE level. Change from Baseline at a particular visit was calculated as the NSE level at that visit minus Baseline.
Measured: 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
Blood samples will be taken to evaluate the pharmacokinetics by assessing plasma concentration of PDR001 at selected time points
Measured: 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
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
The EORTC QLQ-C30 is a patient completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale. Global health status/QoL response options are 1 to 4. Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning.
Change from Baseline was calculated by subtracting Baseline value from the selected visit value. A positive change from Baseline indicates improvement.
Measured: 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
The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of these dimensions, the participant self-assigned a score: from 1 (no problems) to 5 (extreme problems). The 5 digit health states obtained for each dimension was converted into a single mean index value based on the EQ-5D crosswalk value set for the UK using the time trade-off method. This index ranges from -0.594 (worst health) to 1.0 (best health). Change from Baseline was calculated by subtracting Baseline value from the selected visit value. A positive change from baseline indicates improvement.
Measured: 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
ADA prevalence at baseline was calculated as the proportion of participants who had an ADA positive result at baseline
Measured: Baseline
PDR001 ADA Incidence On-treatment
ADA incidence on treatment was calculated as the proportion of participants who were treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2016 (estimated)
- Study start14 Feb 2017
- Primary completion10 Aug 2018
- Study completion13 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Well-differentiated Non-functional NET of Thoracic OriginStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02955069
- Sponsor's protocol ID
- CPDR001E2201
- Other IDs
- 2016-002522-36, 2016
- Status last verified
- Mar 2021
- First submitted
- 2 Nov 2016
- Last updated
- 12 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02955069
- Acronym / sponsor ID
- CPDR001E2201
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 14 Feb 2017 (actual)
- Primary completion
- 10 Aug 2018 (actual)
- Study completion
- 13 May 2020 (actual)
- First posted
- 4 Nov 2016 (estimated)
- Results
- Posted 12 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PDR001 | Experimental | Drug: PDR001Subjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PDR001Also: SpartalizumabPDR001 was administered at a dose of 400 mg via intravenous infusion once every 4 weeks (Q4W). PDR001 was administered on Day 1 of every cycle. Each cycle was 28 days. | Drug | PDR001 |
Primary outcome
Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC).
Time frame: 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.
17 secondary outcomes
Duration of Response (DOR) by RECIST 1.1 and as Per BIRC
Time frame: 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
Time frame: From baseline up to approximately 1.5 years
Time to Response (TTR) by RECIST 1.1 and as Per BIRC
Time frame: From baseline to the first documented response, assessed up to approximately 1.5 years
Progression-free Survival (PFS) by RECIST 1.1 and as Per BIRC
Time frame: 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 Overall Response Rate (irORR) by irRECIST and as Per BIRC
Time frame: From baseline up to approximately 1.5 years
Immune Related Duration of Response (irDoR) by irRECIST and as Per BIRC.
Time frame: From the date of first documented confirmed response (irCR or irPR) until the first documented progression, assessed up to approximately 1.5 years
Immune Related Time to Response (irTTR) by irRECIST and as Per BIRC
Time frame: 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
Time frame: From baseline up to approximately 1.5 years
Immune Related Progression Free Survival (irPFS) by irRECIST and as Per BIRC
Time frame: 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
Overall Survival (OS)
Time frame: From baseline until death due to any cause, assessed up to approx. 3 years
Changes From Baseline in Chromogranin A (CgA) Levels
Time frame: 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
Time frame: 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
Time frame: 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
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
Time frame: 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
Time frame: 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
Time frame: Baseline
PDR001 ADA Incidence On-treatment
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
35 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PDR001 in people with Well-differentiated Non-functional NET of Thoracic Origin and Well-differentiated Non-functional NET of Gastrointestinal Origin, run by Novartis Pharmaceuticals at 35 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Italy, Germany, Japan, France and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC). (time frame: From baseline up to approximately 1.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2021.