Trial Outcomes & Findings for 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) (NCT NCT02955069)

Last Updated: 2021-04-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

116 participants

Primary outcome timeframe

From baseline up to approximately 1.5 years

Results posted on

2021-04-12

Participant Flow

Recruitment took place in 35 investigative sites in 12 countries from 14 Feb 2017 to 04 Apr 2018

A total of 149 participants were screened. Those participants who met the eligibility criteria entered the treatment period.

Participant milestones

Participant milestones
Measure	Well-differentiated NET Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Overall Study STARTED	95	21
Overall Study Full Analysis Set (FAS)	95	21
Overall Study Safety Set	95	21
Overall Study Pharmacokinetic Analysis Set (PAS)	94	18
Overall Study Immunogenicity (IG) Prevalence Set	94	21
Overall Study IG Incidence Set	84	17
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	95	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Well-differentiated NET Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Overall Study Adverse Event	7	2
Overall Study Death	7	3
Overall Study Physician Decision	10	2
Overall Study Progressive disease	64	13
Overall Study Study terminated by sponsor	4	0
Overall Study Subject/Guardian decision	3	1

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.	Total n=116 Participants Total of all reporting groups
Age, Continuous	59.4 Years STANDARD_DEVIATION 11.21 • n=5 Participants	57.4 Years STANDARD_DEVIATION 8.56 • n=7 Participants	59.0 Years STANDARD_DEVIATION 10.77 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	4 Participants n=7 Participants	47 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	17 Participants n=7 Participants	69 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	59 Participants n=5 Participants	16 Participants n=7 Participants	75 Participants n=5 Participants
Race/Ethnicity, Customized Black	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Native American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	15 Participants n=5 Participants	1 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline up to approximately 1.5 years

Population: The FAS comprised of all subjects to whom study treatment had been assigned and who received at least one dose of PDR001 (including incomplete infusion).

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Overall Response Rate (ORR) by RECIST 1.1 and as Per Blinded Independent Central Review (BIRC).	7.4 Percentage of participants Interval 3.0 to 14.6	4.8 Percentage of participants Interval 0.1 to 23.8

SECONDARY outcome

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

Population: Participants in the FAS with confirmed CR or PR

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.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=7 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=1 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Duration of Response (DOR) by RECIST 1.1 and as Per BIRC	250 Days Interval 49.0 to 288.0	270 Days Interval 270.0 to 270.0

SECONDARY outcome

Timeframe: From baseline up to approximately 1.5 years

Population: The FAS comprised of all subjects to whom study treatment had been assigned and who received at least one dose of PDR001 (including incomplete infusion).

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.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Disease Control Rate by RECIST 1.1 and as Per BIRC	64.2 Percentage of participants Interval 53.7 to 73.8	19.0 Percentage of participants Interval 5.4 to 41.9

SECONDARY outcome

Timeframe: From baseline to the first documented response, assessed up to approximately 1.5 years

Population: Participants in the FAS with confirmed CR or PR.

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.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=7 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=1 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Time to Response (TTR) by RECIST 1.1 and as Per BIRC	110 Days Interval 52.0 to 218.0	53 Days Interval 53.0 to 53.0

SECONDARY outcome

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

Population: The FAS comprised of all subjects to whom study treatment had been assigned and who received at least one dose of PDR001 (including incomplete infusion).

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.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Progression-free Survival (PFS) by RECIST 1.1 and as Per BIRC	3.8 Months Interval 3.6 to 5.5	1.8 Months Interval 1.5 to 2.0

SECONDARY outcome

Timeframe: From baseline up to approximately 1.5 years

Population: The FAS comprised of all subjects to whom study treatment had been assigned and who received at least one dose of PDR001 (including incomplete infusion).

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).

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Immune Related Overall Response Rate (irORR) by irRECIST and as Per BIRC	7.4 Percentage of participants Interval 3.0 to 14.6	4.8 Percentage of participants Interval 0.1 to 23.8

SECONDARY outcome

Timeframe: From the date of first documented confirmed response (irCR or irPR) until the first documented progression, assessed up to approximately 1.5 years

Population: Participants in the FAS with confirmed irCR or irPR

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

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=7 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=1 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Immune Related Duration of Response (irDoR) by irRECIST and as Per BIRC.	228 Days Interval 49.0 to 288.0	270 Days Interval 270.0 to 270.0

SECONDARY outcome

Timeframe: From baseline to the first documented response, assessed up to approximately 1.5 years

Population: Participants in the FAS with confirmed irCR or irPR

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.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=7 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=1 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Immune Related Time to Response (irTTR) by irRECIST and as Per BIRC	110 Days Interval 52.0 to 218.0	53 Days Interval 53.0 to 53.0

SECONDARY outcome

Timeframe: From baseline up to approximately 1.5 years

Population: The FAS comprised of all subjects to whom study treatment had been assigned and who received at least one dose of PDR001 (including incomplete infusion).

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.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Immune Related Disease Control Rate (irDCR) by irRECIST and as Per BIRC	66.3 Percentage of participants Interval 55.9 to 75.7	19.0 Percentage of participants Interval 5.4 to 41.9

SECONDARY outcome

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

Population: The FAS comprised of all subjects to whom study treatment had been assigned and who received at least one dose of PDR001 (including incomplete infusion).

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.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Immune Related Progression Free Survival (irPFS) by irRECIST and as Per BIRC	3.8 Months Interval 3.6 to 5.5	1.8 Months Interval 1.5 to 2.0

SECONDARY outcome

Timeframe: From baseline until death due to any cause, assessed up to approx. 3 years

Population: The FAS comprised of all subjects to whom study treatment had been assigned and who received at least one dose of PDR001 (including incomplete infusion).

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.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Overall Survival (OS)	23.4 Months Interval 19.2 to NA: Upper limit was not evaluable	6.8 Months Interval 4.0 to 8.6

SECONDARY outcome

Timeframe: Baseline, day 1 of each cycle from Cycle 2 to end of treatment, assessed up to approx. 1.5 years. Cycle=28 days.

Population: The FAS comprised of all subjects to whom study treatment had been assigned and who received at least one dose of PDR001 (including incomplete infusion). Number analyzed signified number of participants with available data for this outcome measure at specified timepoints.

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.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, day 1 of each cycle from Cycle 2 to end of treatment, assessed up to approx. 1.5 years. Cycle= 28days

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.

Outcome measures

SECONDARY outcome

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

Population: The PAS comprised of all subjects who provide at least one evaluable PDR001 PK concentration. Number analyzed signified number of participants with available data for this outcome measure at specified timepoints.

Blood samples will be taken to evaluate the pharmacokinetics by assessing plasma concentration of PDR001 at selected time points

Outcome measures

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
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 Cycle 3 Day 1	-1.00 score on a scale Standard Deviation 19.491	-11.11 score on a scale Standard Deviation 27.003
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 Cycle 5 Day 1	-1.91 score on a scale Standard Deviation 27.838	-4.17 score on a scale Standard Deviation 17.347
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 Cycle 7 Day 1	1.96 score on a scale Standard Deviation 29.945	25.00 score on a scale Standard Deviation 35.355
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 Cycle 9 Day 1	1.67 score on a scale Standard Deviation 31.823	33.33 score on a scale Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
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 Cycle 11 Day 1	-1.19 score on a scale Standard Deviation 28.048	—
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 Cycle 13 Day 1	1.96 score on a scale Standard Deviation 27.088	41.67 score on a scale Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
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 Cycle 16 Day 1	-16.67 score on a scale Standard Deviation 16.667	—
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 End of Treatment	-6.46 score on a scale Standard Deviation 23.607	-22.92 score on a scale Standard Deviation 23.465

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Change From Baseline in EQ-5D-5L Index Score Cycle 3 Day 1	0.03 score on a scale Standard Deviation 0.169	-0.09 score on a scale Standard Deviation 0.157
Change From Baseline in EQ-5D-5L Index Score Cycle 5 Day 1	-0.02 score on a scale Standard Deviation 0.247	0.02 score on a scale Standard Deviation 0.111
Change From Baseline in EQ-5D-5L Index Score Cycle 7 Day 1	-0.04 score on a scale Standard Deviation 0.241	0.16 score on a scale Standard Deviation 0.135
Change From Baseline in EQ-5D-5L Index Score Cycle 9 Day 1	0.02 score on a scale Standard Deviation 0.247	0.02 score on a scale Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Change From Baseline in EQ-5D-5L Index Score Cycle 11 Day 1	0.02 score on a scale Standard Deviation 0.262	—
Change From Baseline in EQ-5D-5L Index Score Cycle 13 Day 1	-0.03 score on a scale Standard Deviation 0.299	0.03 score on a scale Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Change From Baseline in EQ-5D-5L Index Score Cycle 16 Day 1	-0.17 score on a scale Standard Deviation 0.085	—
Change From Baseline in EQ-5D-5L Index Score End of treatment	-0.10 score on a scale Standard Deviation 0.209	-0.30 score on a scale Standard Deviation 0.263

SECONDARY outcome

Timeframe: Baseline

Population: Participants in the Immunogenicity (IG) set with at least one determinant sample (sample that is neither ADA-inconclusive nor unevaluable) at baseline.

ADA prevalence at baseline was calculated as the proportion of participants who had an ADA positive result at baseline

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=88 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=17 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
PDR001 Anti-drug Antibodies (ADA) Prevalence at Baseline	1 Participants	0 Participants

SECONDARY outcome

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

Population: The IG incidence set comprised of all subjects in the IG prevalence set with a determinant baseline IG sample and at least one determinant post-baseline IG sample. Determinant sample: sample that is neither ADA-inconclusive nor unevaluable.

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)

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=84 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=17 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
PDR001 ADA Incidence On-treatment	10 Participants	2 Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: The Safety Set comprised all subjects who received at least one dose of PDR001

Deaths on-treatment are collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of approximately 3 years. Total Deaths are collected from first dose of study treatment until end of post-treatment efficacy or survival follow, up to maximum duration of approximately 3 years.

Outcome measures

Outcome measures
Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
All Collected Deaths Total Deaths	47 Participants	16 Participants
All Collected Deaths Deaths on-treatment	1 Participants	1 Participants

Adverse Events

Well-differentiated NET

Serious events: 29 serious events

Other events: 86 other events

Deaths: 1 deaths

Poorly-differentiated GEP-NEC

Serious events: 6 serious events

Other events: 18 other events

Deaths: 1 deaths

All Subjects

Serious events: 35 serious events

Other events: 104 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Study director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 4 Day 1	579.9 microgram/liter (ug/L) Standard Deviation 13437.06	1544.5 microgram/liter (ug/L) Standard Deviation 2712.23
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 5 Day 1	598.2 microgram/liter (ug/L) Standard Deviation 11724.93	1306.6 microgram/liter (ug/L) Standard Deviation 3125.84
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 6 Day 1	1337.6 microgram/liter (ug/L) Standard Deviation 7106.32	4531.7 microgram/liter (ug/L) Standard Deviation 8694.65
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 7 Day 1	-564.5 microgram/liter (ug/L) Standard Deviation 12643.71	11089.5 microgram/liter (ug/L) Standard Deviation 17551.10
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 8 Day 1	3726.0 microgram/liter (ug/L) Standard Deviation 18813.63	9103.5 microgram/liter (ug/L) Standard Deviation 14759.44
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 9 Day 1	22522.2 microgram/liter (ug/L) Standard Deviation 94054.85	-1342.0 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 10 Day 1	54301.5 microgram/liter (ug/L) Standard Deviation 250229.27	-1376.0 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 11 Day 1	84634.7 microgram/liter (ug/L) Standard Deviation 344244.60	-1393.0 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 16 Day 1	-81.0 microgram/liter (ug/L) Standard Deviation 1583.99	—
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 17 Day 1	-176.0 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed	—
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 18 Day 1	42.0 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed	—
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 2 Day 1	874.6 microgram/liter (ug/L) Standard Deviation 6694.64	6466.9 microgram/liter (ug/L) Standard Deviation 23760.13
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 3 Day 1	-1811.7 microgram/liter (ug/L) Standard Deviation 21413.11	706.5 microgram/liter (ug/L) Standard Deviation 2294.87
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 12 Day 1	8177.6 microgram/liter (ug/L) Standard Deviation 36820.47	-1362.0 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 13 Day 1	-379.8 microgram/liter (ug/L) Standard Deviation 1509.95	-1377.0 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 14 Day 1	398.3 microgram/liter (ug/L) Standard Deviation 1866.56	—
Changes From Baseline in Chromogranin A (CgA) Levels Cycle 15 Day 1	13.1 microgram/liter (ug/L) Standard Deviation 1120.60	—
Changes From Baseline in Chromogranin A (CgA) Levels End of treatment	30115.3 microgram/liter (ug/L) Standard Deviation 131958.16	3899.6 microgram/liter (ug/L) Standard Deviation 7991.40

Measure	Well-differentiated NET n=95 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=21 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 13 Day 1	-3.9 microgram/liter (ug/L) Standard Deviation 24.22	-17.8 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 2 Day 1	0.8 microgram/liter (ug/L) Standard Deviation 29.71	27.9 microgram/liter (ug/L) Standard Deviation 40.77
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 3 Day 1	2.5 microgram/liter (ug/L) Standard Deviation 29.33	32.6 microgram/liter (ug/L) Standard Deviation 56.87
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 4 Day 1	-0.1 microgram/liter (ug/L) Standard Deviation 14.98	21.9 microgram/liter (ug/L) Standard Deviation 21.64
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 5 Day 1	4.8 microgram/liter (ug/L) Standard Deviation 30.34	31.8 microgram/liter (ug/L) Standard Deviation 56.39
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 6 Day 1	-3.6 microgram/liter (ug/L) Standard Deviation 19.18	151.6 microgram/liter (ug/L) Standard Deviation 204.21
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 7 Day 1	7.6 microgram/liter (ug/L) Standard Deviation 39.44	-3.0 microgram/liter (ug/L) Standard Deviation 17.75
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 8 Day 1	1.0 microgram/liter (ug/L) Standard Deviation 22.19	40.4 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 9 Day 1	2.6 microgram/liter (ug/L) Standard Deviation 8.64	-12.7 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 10 Day 1	10.3 microgram/liter (ug/L) Standard Deviation 33.74	-15.0 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 11 Day 1	2.3 microgram/liter (ug/L) Standard Deviation 8.89	—
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 12 Day 1	-2.4 microgram/liter (ug/L) Standard Deviation 23.04	-12.3 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 14 Day 1	-4.5 microgram/liter (ug/L) Standard Deviation 22.71	—
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 15 Day 1	-3.4 microgram/liter (ug/L) Standard Deviation 29.73	—
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 16 Day 1	26.5 microgram/liter (ug/L) Standard Deviation 35.38	—
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 17 Day 1	15.1 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed	—
Change From Baseline in Neuron Specific Enolase (NSE) Levels Cycle 18 Day 1	13.8 microgram/liter (ug/L) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed	—
Change From Baseline in Neuron Specific Enolase (NSE) Levels End of treatment	47.7 microgram/liter (ug/L) Standard Deviation 136.78	44.3 microgram/liter (ug/L) Standard Deviation 66.73

Measure	Well-differentiated NET n=94 Participants Subjects with advanced or metastatic, well-differentiated non-functional NET of GI, pancreatic or thoracic origin that progressed on or after prior available treatments.	Poorly-differentiated GEP-NEC n=18 Participants Subjects with advanced or metastatic poorly-differentiated GEP-NEC that progressed on or after prior available treatments.
PDR001 Plasma Concentration Cycle 3 Day 1 pre-dose	43.7 nanogram/mililiter (ng/mL) Standard Deviation 18.9	42.3 nanogram/mililiter (ng/mL) Standard Deviation 19.6
PDR001 Plasma Concentration Cycle 6 Day 1 pre-dose	58.2 nanogram/mililiter (ng/mL) Standard Deviation 31.6	49.9 nanogram/mililiter (ng/mL) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
PDR001 Plasma Concentration Cycle 7 Day 1 pre-dose	64.3 nanogram/mililiter (ng/mL) Standard Deviation 37.6	66.9 nanogram/mililiter (ng/mL) Standard Deviation 30.1
PDR001 Plasma Concentration Cycle 11 Day 1 pre-dose	69.2 nanogram/mililiter (ng/mL) Standard Deviation 39.1	99.0 nanogram/mililiter (ng/mL) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
PDR001 Plasma Concentration Cycle 1 Day 1 pre-dose	0 nanogram/mililiter (ng/mL) Standard Deviation 0	0 nanogram/mililiter (ng/mL) Standard Deviation 0
PDR001 Plasma Concentration Cycle 1 Day 1 30 min post-dose	106 nanogram/mililiter (ng/mL) Standard Deviation 32.9	100 nanogram/mililiter (ng/mL) Standard Deviation 52.2
PDR001 Plasma Concentration Cycle 2 Day 1 Pre-dose	26.8 nanogram/mililiter (ng/mL) Standard Deviation 9.76	25.8 nanogram/mililiter (ng/mL) Standard Deviation 9.30
PDR001 Plasma Concentration Cycle 3 Day 1 30 min post-dose	140 nanogram/mililiter (ng/mL) Standard Deviation 46.7	142 nanogram/mililiter (ng/mL) Standard Deviation 44.3
PDR001 Plasma Concentration Cycle 4 Day 1 pre-dose	52.8 nanogram/mililiter (ng/mL) Standard Deviation 25.1	40.7 nanogram/mililiter (ng/mL) Standard Deviation 17.2
PDR001 Plasma Concentration Cycle 5 Day 1 pre-dose	52.0 nanogram/mililiter (ng/mL) Standard Deviation 32.3	41.8 nanogram/mililiter (ng/mL) Standard Deviation 8.88
PDR001 Plasma Concentration Cycle 8 Day 1 pre-dose	59.6 nanogram/mililiter (ng/mL) Standard Deviation 38.2	64.7 nanogram/mililiter (ng/mL) Standard Deviation 31.4
PDR001 Plasma Concentration Cycle 9 Day 1 pre-dose	65.1 nanogram/mililiter (ng/mL) Standard Deviation 38.1	93.7 nanogram/mililiter (ng/mL) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
PDR001 Plasma Concentration Cycle 10 Day 1 pre-dose	70.2 nanogram/mililiter (ng/mL) Standard Deviation 40.2	—
PDR001 Plasma Concentration Cycle 12 Day 1 pre-dose	71.7 nanogram/mililiter (ng/mL) Standard Deviation 38.1	111 nanogram/mililiter (ng/mL) Standard Deviation NA NA: Not evaluable due to low number of participants analyzed
PDR001 Plasma Concentration Cycle 13 Day 1 pre-dose	91.8 nanogram/mililiter (ng/mL) Standard Deviation 46.0	—