A Prospective, Open-label, Multi-center, Single Arm, Phase III Study of [68Ga]Ga-DOTA-TATE in the Diagnosis of Patients With Neuroendocrine Neoplasms (NENs) and Healthy Volunteers in Japan
Phase: PHASE3
Conditions: Neuroendocrine Neoplasms
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development 
Clinical Trial Protocol Title: 
A prospective, open-label, multi-center, single arm, phase 
III study of [68Ga]Ga-DOTA-TATE in the diagnosis of 
patients with neuroendocrine neoplasms (NENs) and 
healthy volunteers in Japan 
Clinical Trial Protocol Number: CAAA501A11301 / NCT06240741
Version Number: v01 (Clean) 
Compound: AAA501 
Brief Title: A prospective, open-label study of [68Ga]Ga-DOTA-TATE in patients with 
neuroendocrine neoplasms (NENs) and healthy volunteers in Japan 
Study Phase: III 
Sponsor Name: Novartis, Eckert & Ziegler Radiopharma GmbH 
Regulatory Agency Identifier Number(s): Not applicable 
Approval Date: 29-NOV-2023 (content final) 
Property of Novartis, Eckert & Ziegler Radiopharma GmbH 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis, Eckert & Ziegler Radiopharma GmbH 
Clinical Trial Protocol Template Version 5.0 dated 14-Jan-2022 

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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 6 
List of figures ...................................................................................................................... 6 
Amendment 1 (29-NOV-2023) ........................................................................................... 7 
1 
Protocol summary ................................................................................................................ 8 
1.1 
Summary .................................................................................................................. 8 
1.2 
Schema ................................................................................................................... 12 
1.3 
Schedule of activities (SoA) .................................................................................. 13 
2 
Introduction ....................................................................................................................... 17 
2.1 
Study rationale ....................................................................................................... 17 
2.2 
Background ............................................................................................................ 17 
2.3 
Benefit/Risk assessment ........................................................................................ 18 
3 
Objectives, endpoints, and estimands ................................................................................ 19 
3.1 
Primary estimands ................................................................................................. 21 
3.2 
Secondary estimands ............................................................................................. 22 
4 
Study design ...................................................................................................................... 22 
4.1 
Overall design ........................................................................................................ 22 
4.2 
Scientific rationale for study design ...................................................................... 23 
4.3 
Justification for dose .............................................................................................. 24 
4.4 
Rationale for choice of control drugs (comparator/placebo) or combination 
drugs ...................................................................................................................... 25 
4.5 
Rationale for public health emergency mitigation procedures .............................. 25 
4.6 
Purpose and timing of interim analyses/design adaptations .................................. 25 
4.7 
End of study definition .......................................................................................... 25 
5 
Study population ................................................................................................................ 25 
5.1 
Inclusion criteria .................................................................................................... 25 
5.2 
Exclusion criteria ................................................................................................... 26 
5.3 
Screen failures ....................................................................................................... 26 
5.3.1 
Replacement policy ............................................................................... 27 
5.3.2 
Participant numbering ........................................................................... 27 
6 
Study treatment(s) and concomitant therapy ..................................................................... 27 
6.1 
Study treatment(s) .................................................................................................. 27 
6.1.1 
Additional study treatments .................................................................. 28 
6.1.2 
Treatment arms/group ........................................................................... 28 
6.1.3 
Guidelines for continuation of treatment .............................................. 28 
6.1.4 
Treatment duration ................................................................................ 28 

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6.1.5 
Medical devices ..................................................................................... 29 
6.2 
Preparation, handling, storage, and accountability ................................................ 29 
6.2.1 
Handling of study treatment .................................................................. 29 
6.2.2 
Handling of other treatment .................................................................. 30 
6.2.3 
Instruction for prescribing and taking study treatment ......................... 30 
6.3 
Measures to minimize bias: randomization and blinding ...................................... 30 
6.3.1 
Treatment assignment, randomization .................................................. 30 
6.3.2 
Treatment blinding ................................................................................ 30 
6.3.3 
Emergency breaking of assigned treatment code .................................. 30 
6.4 
Study treatment compliance .................................................................................. 30 
6.5 
Dose modification .................................................................................................. 30 
6.5.1 
Definitions of dose limiting toxicities (DLTs) ...................................... 30 
6.5.2 
Dose modifications ................................................................................ 30 
6.5.3 
Follow-up for toxicities ......................................................................... 30 
6.6 
Continued access to study treatment after the end of the study ............................. 31 
6.6.1 
Post trial access ..................................................................................... 31 
6.7 
Treatment of overdose ........................................................................................... 31 
6.7.1 
Reporting of study treatment errors including misuse/abuse ................ 31 
6.8 
Concomitant and other therapy .............................................................................. 31 
6.8.1 
Concomitant therapy ............................................................................. 32 
6.8.2 
Prohibited medication ........................................................................... 32 
7 
Discontinuation of study treatment and participant discontinuation/withdrawal .............. 32 
7.1 
Discontinuation of study treatment ........................................................................ 32 
7.2 
Participant discontinuation from the study ............................................................ 32 
7.3 
Withdrawal of informed consent and exercise of participants’ data privacy 
rights ...................................................................................................................... 33 
7.4 
Lost to follow-up ................................................................................................... 33 
7.5 
Early study termination by the Sponsor ................................................................. 34 
8 
Study Assessments and Procedures ................................................................................... 34 
8.1 
Screening ............................................................................................................... 34 
8.1.1 
Eligibility screening .............................................................................. 35 
8.2 
Participant demographics/other baseline characteristics ....................................... 35 
8.3 
Efficacy assessments ............................................................................................. 36 
8.3.1 
Imaging for tumor assessment .............................................................. 36 
8.3.2 
Histopathology assessments .................................................................. 37 
8.3.3 
Appropriateness of imaging assessments .............................................. 37 

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8.4 
Safety assessments ................................................................................................. 38 
8.4.1 
Physical examinations ........................................................................... 38 
8.4.2 
Vital signs.............................................................................................. 38 
8.4.3 
Electrocardiograms ............................................................................... 39 
8.4.4 
Clinical safety laboratory tests .............................................................. 40 
8.4.5 
Pregnancy testing .................................................................................. 41 
8.4.6 
Suicidal ideation and behavior risk monitoring .................................... 41 
8.4.7 
Other safety evaluations ........................................................................ 41 
8.4.8 
Appropriateness of safety measurements .............................................. 41 
8.5 
Additional assessments .......................................................................................... 42 
8.5.1 
Clinical Outcome Assessments (COAs) ............................................... 42 
8.5.2 
Imaging ................................................................................................. 42 
8.5.3 
Other assessments ................................................................................. 42 
8.6 
Adverse events (AEs), serious adverse events (SAEs), and other safety 
reporting ................................................................................................................. 42 
8.6.1 
Adverse events ...................................................................................... 42 
8.6.2 
Serious adverse events .......................................................................... 44 
8.6.3 
SAE reporting........................................................................................ 45 
8.6.4 
Pregnancy .............................................................................................. 46 
8.6.5 
Reporting of study treatment errors, study treatment misuse/abuse 
and overdose .......................................................................................... 47 
8.6.6 
Adverse events of special interest ......................................................... 47 
8.7 
Pharmacokinetics ................................................................................................... 47 
8.7.1 
Pharmacokinetic blood collection and handling ................................... 47 
8.7.2 
Analytical method ................................................................................. 48 
8.8 
Biomarkers ............................................................................................................. 48 
8.9 
Immunogenicity assessments ................................................................................. 48 
8.9.1 
Immunogenicity blood sample collection and handling ....................... 48 
8.9.2 
Immunogenicity analytical method(s)................................................... 48 
8.10 
Health economics OR Medical resource utilization and health economics .......... 48 
9 
Statistical considerations ................................................................................................... 48 
9.1 
Analysis sets .......................................................................................................... 49 
9.2 
Statistical analyses ................................................................................................. 49 
9.2.1 
General considerations .......................................................................... 49 
9.2.2 
Participant demographics and other baseline characteristics ................ 50 
9.2.3 
Treatments ............................................................................................. 50 
9.3 
Primary endpoint(s)/estimand(s) analysis .............................................................. 50 

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9.3.1 
Definition of primary endpoint(s) ......................................................... 50 
9.3.2 
Statistical model, hypothesis, and method of analysis .......................... 51 
9.3.3 
Handling of intercurrent events of primary estimand (if applicable) .... 51 
9.3.4 
Handling of missing values not related to intercurrent event ............... 51 
9.3.5 
Multiplicity adjustment (if applicable) .................................................. 51 
9.3.6 
Sensitivity analyses ............................................................................... 51 
9.3.7 
Supplementary analysis ......................................................................... 51 
9.4 
Secondary endpoint(s)/estimand(s) analysis .......................................................... 52 
9.4.1 
Efficacy and/or pharmacodynamic endpoint(s) .................................... 52 
9.4.2 
Safety endpoints .................................................................................... 53 
9.4.3 
Pharmacokinetics .................................................................................. 55 
 
 56 
9.6 
(Other) Safety analyses .......................................................................................... 57 
9.7 
Other analyses ........................................................................................................ 57 
9.8 
Interim analysis ...................................................................................................... 57 
9.9 
Sample size determination ..................................................................................... 57 
9.9.1 
Primary endpoint(s) ............................................................................... 57 
10 Supporting documentation and operational considerations ............................................... 59 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ................... 59 
10.1.1 
Regulatory and ethical considerations .................................................. 59 
10.1.2 
Informed consent process ...................................................................... 60 
10.1.3 
Data protection ...................................................................................... 61 
10.1.4 
Committees structure ............................................................................ 61 
10.1.5 
Data quality assurance ........................................................................... 61 
10.1.6 
Source documents ................................................................................. 63 
10.1.7 
Publication policy.................................................................................. 63 
10.1.8 
Protocol adherence and protocol amendments ...................................... 63 
10.2 
Appendix 2: Abbreviations and definitions ........................................................... 65 
10.2.1 
List of abbreviations .............................................................................. 65 
10.2.2 
Definitions ............................................................................................. 67 
10.3 
Appendix 3: Clinical laboratory tests .................................................................... 71 
10.3.1 
Clinically notable laboratory values and vital signs ............................. 71 
10.4 
Appendix 4: Participant Engagement .................................................................... 72 
10.5 
Appendix 5: Liver safety monitoring .................................................................... 73 
10.5.1 
Liver event and laboratory trigger definitions & follow-up 
requirements .......................................................................................... 73 

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10.6 
Appendix 6: Renal safety monitoring .................................................................... 74 
10.6.1 
Specific Renal Alert Criteria and Actions and Event Follow-up .......... 74 
11 References ......................................................................................................................... 75 
List of tables 
Table 1-1 
Objectives and related endpoints ............................................................ 8 
Table 1-2 
Assessment Schedule ............................................................................ 14 
Table 3-1 
Objectives and related endpoints .......................................................... 19 
Table 6-1 
Investigational and control drug ............................................................ 28 
Table 8-1 
ECOG performance status ..................................................................... 36 
Table 8-2 
Imaging Assessment Collection Plan .................................................... 36 
Table 8-3 
Local ECG collection plan .................................................................... 39 
Table 8-4 
Laboratory assessments ......................................................................... 40 
Table 8-5 
Pharmacokinetic blood collection log ................................................... 48 
Table 9-1 
Sensitivity and Specificity ..................................................................... 50 
Table 9-2 
Non-compartmental pharmacokinetic parameters ................................ 56 
Table 9-3 
Sensitivity of power to changes in number of participants ................... 58 
List of figures 
Figure 1-1 
Study design .......................................................................................... 12 
Figure 8-1 
Timing of study procedures .................................................................. 39 
 

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Protocol No. CAAA501A11301 
 
Amendment 1 (29-NOV-2023)  
As of the release of this protocol amendment, study has not started, and no sites are initiated. 
No participants are enrolled. 
Amendment rationale  
The purpose of this amendment is to: 
• Correct the components of regions for Regional-Level Assessment. 
• Update the clinical laboratory parameters for clarification. 
Other editorial changes, reformatting, and corrections are also made throughout the protocol. 
Changes to the protocol 
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underlined for insertions. 
List of changes to protocol: 
• Section 1.1: Brief Title has been revised to match the Brief Title in the cover page. 
• Table 8-4: Chemistry: “Glucose (fasting)” has been updated to “Plasma Glucose 
(fasting)”. 
• Section 8.9.1: Language in the section has been revised to “Not Applicable”. 
• Section 9.4.1: Regional-Level Assessment: “duodenum” has been revised into 
“gastrointestinal”. 
IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol require IRB/IEC approval prior to 
implementation.  
 

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1 
Protocol summary 
1.1 
Summary 
Protocol Title: 
A prospective, open-label, multi-center, single arm, phase III study of [68Ga]Ga-DOTA-TATE 
in the diagnosis of patients with neuroendocrine neoplasms (NENs) and healthy volunteers in 
Japan 
Brief Title: 
A prospective, open-label study of [68Ga]Ga-DOTA-TATE in patients with neuroendocrine 
neoplasms (NENs) and healthy volunteers in Japan 
Purpose 
To evaluate the diagnostic performance of [68Ga]Ga-DOTA-TATE PET/CT imaging compared 
with conventional imaging (CIM) as standard of truth in patients with neuroendocrine 
neoplasms (NENs) and healthy volunteers (HVs) 
Study Indication /Medical Condition: 
Neuroendocrine neoplasms (NENs) 
Treatment type 
Drug 
Study type 
Interventional 
Objectives, Endpoints, and Estimands: 
Table 1-1 
Objectives and related endpoints 
Objectives 
Endpoints 
Primary 
 
• 
To evaluate the subject-level sensitivity of 
[68Ga]Ga-DOTA-TATE PET/CT imaging for 
NENs. 
• 
Proportion of [68Ga]Ga-DOTA-TATE positive 
participants (TP participants) among CIM 
positive participants (TP or FN participants). 
• 
To evaluate the subject-level specificity of 
[68Ga]Ga-DOTA-TATE PET/CT imaging for 
NENs. 
• 
Proportion of [68Ga]Ga-DOTA-TATE 
negative participants (TN participants) 
among CIM negative participants (TN or FP 
participants). 
Secondary 
 
• 
To evaluate subject-level positive predictive 
values (PPV) of [68Ga]Ga-DOTA-TATE 
PET/CT imaging. 
• 
Proportion of participants who are positive 
on both [68Ga]Ga-DOTA-TATE PET/CT 
imaging and CIM (TP participants) among 

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participants who are positive on [68Ga]Ga-
DOTA-TATE PET/CT imaging (TP or FP 
participants). 
• 
To evaluate subject-level negative predictive 
values (NPV) of [68Ga]Ga-DOTA-TATE 
PET/CT imaging. 
• 
Proportion of participants who are negative 
on both [68Ga]Ga-DOTA-TATE PET/CT 
imaging and CIM (TN participants) among 
participants who are negative on [68Ga]Ga-
DOTA-TATE PET/CT imaging (TN or FN 
participants). 
• 
To evaluate subject-level accuracy of 
[68Ga]Ga-DOTA-TATE PET/CT imaging. 
• 
Proportion of participants who have 
consistent results (i.e. TP or TN participants) 
among all participants assessed by 
[68Ga]Ga-DOTA-TATE PET/CT imaging and 
CIM 
• 
To evaluate region-level sensitivity of 
[68Ga]Ga-DOTA-TATE PET/CT imaging for 
NENs. 
• 
Proportion of [68Ga]Ga-DOTA-TATE positive 
regions (TP regions) among CIM positive 
regions (TP or FN regions). 
• 
To evaluate region-level specificity of 
[68Ga]Ga-DOTA-TATE PET/CT imaging for 
NENs. 
• 
Proportion of [68Ga]Ga-DOTA-TATE 
negative regions (TN regions) among CIM 
negative regions (TN or FP regions). 
• 
To evaluate region-level positive predictive 
values (PPV) of [68Ga]Ga-DOTA-TATE 
PET/CT imaging. 
• 
Proportion of regions which are positive on 
both [68Ga]Ga-DOTA-TATE PET/CT 
imagings and CIM (TP regions) among 
regions which are positive on [68Ga]Ga-
DOTA-TATE PET/CT imaging (TP or FP 
regions). 
• 
To evaluate region-level negative predictive 
values (NPV) of [68Ga]Ga-DOTA-TATE 
PET/CT imaging. 
• 
Proportion of regions which are negative on 
both [68Ga]Ga-DOTA-TATE PET/CT imaging 
and CIM (TN regions) among regions which 
are negative on [68Ga]Ga-DOTA-TATE 
PET/CT imaging (TN or FN regions). 
• 
To evaluate region-level accuracy of 
[68Ga]Ga-DOTA-TATE PET/CT imaging. 
• 
Proportion of regions which have consistent 
results (i.e. TP or TN regions) among all 
regions assessed by [68Ga]Ga-DOTA-TATE 
PET/CT imaging and CIM 
• 
To evaluate the number of lesions detected 
by [68Ga]Ga-DOTA-TATE PET/CT imaging 
and each CIM at region-level. 
• 
Number of lesions detected by [68Ga]Ga-
DOTA-TATE PET/CT imaging and each CIM 
at region-level. 
• 
To evaluate the impact of [68Ga]Ga-DOTA-
TATE PET/CT imaging on treatment 
decision. 
• 
Percentage of patients who underwent a 
change in intended treatment plan attributed 
to the [68Ga]Ga-DOTA-TATE imaging as 
assessed by pre and post imaging 
questionnaires. 
• 
To evaluate inter-reader variability. 
• 
Inter-reader agreement on  [68Ga]Ga-DOTA-
TATE PET/CT imaging. 
• 
To evaluate safety and tolerability of 
[68Ga]Ga-DOTA-TATE. 
• 
Incidence of Treatment emergent adverse 
event (TEAE) rate within 8 days after 
[68Ga]Ga-DOTA-TATE administration. 
• 
To evaluate PK of [68Ga]Ga-DOTA-TATE. 
• 
Pharmacokinetic parameters (AUCinf, 
AUClast, Cmax, Tmax, T1/2, CL, Vz etc.). 

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• 
To evaluate lesion-level concordance for 
somatostatin receptor (SSTR) between 
[68Ga]Ga-DOTA-TATE PET/CT imaging 
local read and local histopathology results. 
• 
Lesion-level concordance rate for SSTR 
between [68Ga]Ga-DOTA-TATE PET/CT 
imaging local read and local histopathology 
result among lesions that local 
histopathology result are available. 
Trial Design: 
This is a prospective, open-label, multi-center, single arm, phase III study to evaluate the 
diagnostic performance of [68Ga]Ga-DOTA-TATE PET/CT imaging compared with 
conventional imaging (CIM) including High Resolution CT with contrast (or MRI if CT with 
contrast is medically contraindicated) and [111In]In-Pentetreotide SPECT/CT as standard of 
truth in patients with NENs and HVs. 
Approximately 47 patients with NENs and 23 HVs will be enrolled. Of all the participants with 
NENs, the number of participants with suspected NENs is limited to up to 5 with negative CIM 
by central read. Negative CIM by central read is applicable for patients who do not show any 
lesions based on CIM by central read. [68Ga]Ga-DOTA-TATE PET/CT imaging will be read 
by 3 independent readers who will be blinded to any other participant’s data including CIM. In 
addition, CIM as standard of truth will be read by an independent reader who will be blinded to 
[68Ga]Ga-DOTA-TATE PET/CT imaging and any other participant’s data. 
Brief Summary: 
The purpose of this study is to evaluate the diagnostic performance of [68Ga]Ga-DOTA-TATE 
PET/CT imaging compared with CIM as standard of truth in patients with NENs and HVs. The 

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data from this study will provide the evidence for diagnosis of [68Ga]Ga-DOTA-TATE PET/CT 
imaging in patient with NENs in Japan. 
All enrolled participants will undergo [68Ga]Ga-DOTA-TATE PET/CT imaging. [68Ga]Ga-
DOTA-TATE will be administered intravenously at a dose of 2 MBq/kg (0.054 mCi/kg) of 
body weight up to a maximum total dose of 200 MBq (5.4 mCi), and PET/CT imaging will be 
acquired 40 to 90 minutes after the intravenous administration of [68Ga]Ga-DOTA-TATE. 
• Duration of screening period is up to 35 days 
• Imaging period will be completed within one day followed by safety follow up visit (Day 
8) after imaging day (Day 1) 
Treatment of interest 
[68Ga]Ga-DOTA-TATE will be administered intravenously at a dose of 2 MBq/kg (0.054 
mCi/kg) of body weight up to a maximum total dose of 200 MBq (5.4 mCi), and PET/CT 
imaging will be acquired 40 to 90 minutes after the intravenous injection of [68Ga]Ga-DOTA-
TATE. 
Number of Participants 
Approximately 70 participants (47 patients with NENs and 23 HVs) will be enrolled. Of all the 
participants with NENs, the number of participants with suspected NENs is limited to up to 5 
patients with negative CIM by central read. 
Key Inclusion criteria 
1. Signed informed consent must be obtained prior to participation in the study 
2. Participants must be adults ≥ 18 years of age 
3. ECOG performance status 0-2 
4. For patient with NENs only: Participants with confirmed NENs based on histopathology, 
imaging and other relevant examination, or with suspected NENs which localization cannot be 
confirmed by CIM 
5. For HVs only: Male or female participant in good health condition as determined by no 
clinically significant findings from medical history, physical examination, vital signs, lab test 
and ECG 
Key Exclusion criteria 
1. Inability to complete the needed investigational and conventional imaging due to any reason 
(severe claustrophobia, inability to lie still for the entire imaging time, etc.) 
2. Any additional medical condition, serious intercurrent illness, concomitant cancer or other 
extenuating circumstance that, in the opinion of the Investigator, would indicate a significant 
risk to safety or impair study participation 
3. Known allergy, hypersensitivity, or intolerance to [68Ga]Ga-DOTA-TATE and [111In]In-
Pentetreotide 

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4. Therapeutic use of any somatostatin analogue except for the following washout period 
• Short-acting analogs of somatostatin can be used up to 24 hours before injection of [68Ga]Ga-
DOTA-TATE. 
• Long-acting analogs of somatostatin can be used up to 28 days before injection of [68Ga]Ga-
DOTA-TATE.  
5. Prior administration of a radiopharmaceutical unless 10 or more half-lives have elapsed 
before injection of [68Ga]Ga-DOTA-TATE 
6. Use of other investigational drugs within 30 days before screening 
Treatment Groups: 
All screening procedures must be completed within 35 days prior to imaging day. Enrollment 
should occur within the 35-days screening period once all eligibility criteria are met. 
All enrolled participants will undergo [68Ga]Ga-DOTA-TATE PET/CT imaging and come back 
to the hospital at safety follow up visit (Day 8) after imaging day (Day 1) for safety follow up 
assessment. 
Data Monitoring/Other Committee: 
Not applicable. 
Key words 
 [68Ga]Ga-DOTA-TATE, 
Neuroendocrine 
Neoplasms 
(NENs), 
PET/CT, 
Diagnostic 
performance, Sensitivity, Specificity 
1.2 
Schema 
Figure 1-1 
Study design 
 

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NENs: Neuroendcrine neoplasms, CT: Computed Tomography, MRI: Magnetic Resonance Imaging, 
CIM: Conventional Imaging, PET: Positron Emission Tomography 
1.3 
Schedule of activities (SoA) 
The SoA lists all of the assessments and when they are performed. All data obtained from these 
assessments must be supported in the participant’s source documentation. The “X” in the table 
denotes the assessments to be recorded in the clinical database or received electronically from 
a vendor. The “S” in the table denotes the assessments that are only in the participant’s source 
documentation and do not need to be recorded in the clinical database. 
Participants should be seen for all visits/assessments as outlined in the SoA or as close to the 
designated day/time as possible. Missed or rescheduled visits should not lead to automatic 
discontinuation. 
Participants who discontinue from study should be scheduled for a final evaluation visit if they 
agree, as soon as possible, at which time all of the assessments listed for the final visit will be 
performed. At this final visit, the adverse events and concomitant medications not previously 
reported must be recorded on the electronic Case Report Form (eCRF). 
The preferred sequence of cardiovascular data collection during study visits is ECG collection 
first, while patient is at rest, followed by vital signs, and blood sampling. 
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e. pandemic, epidemic or natural disaster that limits or prevents on-site study visits, alternative 
methods of providing continuing care may be implemented by the Investigator as the situation 
dictates. If allowable by a local health authority, national and local regulations and depending 
on operational capabilities, phone calls, virtual contacts (e.g. tele consultation) or visits by site 
staff/ off-site healthcare professional(s) staff to the participant´s home, can replace certain 
protocol assessments, for the duration of the disruption until it is safe for the participant to visit 
the site again. If the Investigator delegates tasks to an off-site healthcare professional, the 
Investigator must ensure the individual(s) is/are qualified and appropriately trained to perform 
assigned duties. The Investigator must oversee their conduct and remain responsible for the 
evaluation of the data collected. 

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Period 
Screening 
Treatment 
Post-Treatment Follow-Up 
Visit Name 
Screening 
Imaging day 
Safety follow up 
EOS 
Days 
-35 to -1 
1 
8 
±1 
30 
Time (post-dose) 
- 
Pre-injection 
Injection 
Post-injection 
- 
- 
Disposition 
X 
  
  
X 
  
X 
X Assessment to be recorded in the clinical database or received electronically from a vendor 
S Assessment to be recorded in the source documentation only 
1 Only for the patients with NENs 
2 In case definitive diagnosis has not been confirmed at Screening, this will be performed at Treatment, Post-Treatment Follow-Up and even after EOS and documented 
in eCRF. 
3 Please refer to Table 8-5 regarding the time points. 
4 CIM assessment performed as a part of clinical practice within 2 months prior to imaging day even before informed consent, can be used as standard reference as long 
as imaging quality meets study defined criteria. 
5 If SPECT/CT is not available in the clinical site, SPECT can be acceptable. 
6 Imaging will be acquired 40 to 90 minutes after the intravenous administration 
7 In case pathology from retrospective biopsy even before informed consent is available, the result can be evaluated. 
8 If indicated, biopsy/surgery should be performed within 30 days after Imaging day. 

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2 
Introduction 
2.1 
Study rationale 
The purpose of this study is to evaluate the diagnostic performance of [68Ga]Ga-DOTA-TATE 
PET/CT imaging compared with CIM as standard of truth in patients with NENs and HVs. The 
data from this study will provide the evidence for the diagnostic use of [68Ga]Ga-DOTA-TATE 
PET/CT imaging in patients with NENs in Japan. 
2.2 
Background 
NENs are malignant tumors that develop in the lungs, gastrointestinal tract, and other organs 
and show various clinical symptoms. The most common primary site varies by race, with the 
lung being the most common in white patients, and the rectum being the most common in Asian 
patients (Yao et al 2008). Gastroenteropancreatic NENs are common in the Japanese population 
and the age-adjusted incidence rate of gastroenteropancreatic NENs was approximately 3.5 
cases/year per 100,000 people in Japan (Masui et al 2020). Neuroendocrine markers 
(synaptophysin, 
chromogranin 
A, 
etc.), 
various 
diagnostic 
imaging 
technologies 
(ultrasonography, CT, MRI, FDG-PET/CT, somatostatin receptor (SSTR) scintigraphy), and 
histopathologies 
are 
used 
in 
diagnosis 
of 
NENs (Clinical Practice Guidelines for Gastroenteropancreatic Neuroendocrine Neoplasms 20
19). The treatment of NENs is mainly radical surgery and drug therapy, and the first-line 
curative treatment is surgical resection when tumors are localized. Hence, accurate localization 
diagnosis and disease staging are important to determine the indication for surgery. 
A distinct feature shared by NENs is the over-expression of SSTRs, particularly SSTR type 2 
(SSTR2), on the membrane's plasma, which makes SSTRs suitable molecular targets for 
specific diagnostic and therapeutic ligands (Reubi 2003, Volante et al 2007). This has led to the 
approval of [177Lu]Lu-DOTA-TATE, a radioligand therapy targeting SSTR, in Japan in 2021 
for the indication of "somatostatin receptor-positive neuroendocrine tumors". In order to select 
appropriate patients for this new drug therapy, it is important to confirm the SSTR expression. 
SSTR imagings are widely used to identify SSTR-positive lesions or to evaluate the expression 
of SSTR in lesions.  [111In]In-Pentetreotide was firstly approved in US in 1994 and had been 
used around the world over the past decades. Recently, the metallic positron emitter, gallium 
(68Ga), has become of great interest because of its suitable radiophysical properties; its positron 
yield is high and accounts for 89% of all disintegrations. The radionuclide has a half-life of 68 
min matching the pharmacokinetics of many peptides and other small molecules which have 
rapid blood clearance, quick diffusion and target localization. 68Ga-labeled somatostatin 
analogues such as, [68Ga]Ga-DOTA-TOC, [68Ga]Ga-DOTA-NOC and [68Ga]Ga-DOTA-TATE, 
have been largely tested in preclinical and clinical settings, showing high binding affinity to 
SSTR2 
and 
good 
uptake 
in 
SSTR2-expressing 
NENs 
(Reubi et al 2000, Froidevaux et al 2002, Antunes et al 2007) , and became the gold standard 
imaging 
for 
the 
patient 
with 
SSTR 
positive 
NENs 
(Ambrosini et al 2022, NCCN Guidelines 2022, 
Pavel et al 2020, 
Sundin et al 2017, 
Hope et al 2023). In Japan, [111In]In-Pentetreotide was approved as a radiopharmaceutical for 

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the indication of "somatostatin receptor scintigraphy in the diagnosis of neuroendocrine 
neoplasms" in 2015, but any 68Ga-labeled somatostatin analogues has not been approved yet. 
[68Ga]Ga-DOTA-TATE 
[68Ga]Ga-DOTA-TATE is a radiolabeled somatostatin analog that has high affinity for SSTR2. 
It is composed of the somatostatin peptide analog Octreotate, coupled to the metal-ion chelating 
moiety DOTA. It can be radiolabeled with 68Ga for molecular imaging with PET and binds to 
cells expressing SSTR. NetSpot® (Gallium Ga 68 dotate (USAN)) is a kit for 
radiopharmaceutical preparation of [68Ga]Ga-DOTA-TATE, approved in the USA, Canada and 
Switzerland for the localization of SSTR-positive neuroendocrine tumors (NETs) after 
radiolabeling with 68Ga. 
Several clinical studies with [68Ga]Ga-DOTA-TATE have been published. Srirajaskanthan et 
al. (Srirajaskanthan et al 2010) demonstrated that in patients with negative or equivocal 
[111In]In-Pentetreotide findings, [68Ga]Ga-DOTA-TATE PET identifies additional lesions and 
may alter management in many cases. Kabasakal et al. (Kabasakal et al 2012) compared 
[68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-NOC, which were found to have similar 
diagnostic accuracy. However, [68Ga]Ga-DOTA-TATE seems to have a higher lesion uptake 
and may have a potential advantage. In another study, Wild et al. (Wild et al 2013) indicated 
that [68Ga]Ga-DOTA-NOC had greater sensitivity for detecting liver metastases, but [68Ga]Ga-
DOTA-TATE showed greater sensitivity detecting bone metastases. Furthermore, the 
investigators found that [68Ga]Ga-DOTA-TATE had lower background activity, resulting in 
better imaging properties (ability to detect faint lesions). Hofman et al. and Walker et al. 
(Hofman et al 2012, Walker et al 2013) described the dosimetry of [68Ga]Ga-DOTA-TATE 
and demonstrated that patient radiation exposure from [68Ga]Ga-DOTA-TATE is lower than 
that from [111In]In-Pentetreotide for a whole-body scan. [68Ga]Ga-DOTA-TATE also provides 
superior image quality compared to [111In]In-Pentetreotide while significantly shortening 
examination time by a full day.  
Schmid-Tannwald et al. (Schmid-Tannwald et al 2013) demonstrated the superior sensitivity of 
[68Ga]Ga-DOTA-TATE PET/CT compared to MRI in the detection of pancreatic NETs. 
A study from Sandström et al. (Sandström et al 2013) explored the biodistribution and radiation 
dosimetry of [68Ga]Ga-DOTA-TATE compared to [68Ga]Ga-DOTA-TOC. The study found that 
the effective radiation dose for a 100 MBq administration was identical for both compounds. 
With respect to biodistribution, there was little difference between the two compounds, with 
[68Ga]Ga-DOTA-TATE showing a somewhat slower washout from liver (possibly due to the 
result of slightly greater retention in liver metastases which were present in the majority of 
patients). 
Further details on [68Ga]Ga-DOTA-TATE can be found in the Investigator's Brochure (IB). 
2.3 
Benefit/Risk assessment 
Various retrospective and prospective studies provided the evidence of significant diagnostic 
benefit for  [68Ga]Ga-DOTA-TATE (Refer to Section 2.2 and Investigator's Brochure). 
The published data and report from commercial use consistently demonstrates that imaging with 
[68Ga]Ga-DOTA-TATE is well tolerated. No serious or severe adverse events were observed, 

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and no participants had a trial related event requiring additional medical care 
(Deppen et al 2016b). The number of patients exposed to [68Ga]Ga-DOTA-TATE can be 
estimated as 171,613 cumulatively until 30-Nov-2022 in the post marketing experience. There 
is no new or changing safety signal; the benefit/risk assessment was considered to remain 
favorable and unchanged. 
[68Ga]Ga-DOTA-TATE contributes to a participant’s overall long-term cumulative radiation 
exposure. Long-term cumulative radiation exposure is associated with an increased risk for 
cancer. 
As this is a diagnostic study participants enrolled are not expected to derive direct benefit even 
though it is expected that new lesions maybe identified in some participants as a consequence 
of this study and these participants may benefit from a more appropriate management plan. 
The risk to participants in this trial may be minimized by compliance with the eligibility criteria 
and study procedures, as well as close clinical monitoring. Appropriate eligibility criteria are 
included in this protocol. 
The risk-benefit ratio is expected to be favorable to [68Ga]Ga-DOTA-TATE. Additional details 
of the nonclinical and clinical experience with [68Ga]Ga-DOTA-TATE are provided in the IB. 
3 
Objectives, endpoints, and estimands 
Endpoints will be evaluated based on central read unless otherwise specified. 
Table 3-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
• 
To evaluate the subject-level sensitivity 
of [68Ga]Ga-DOTA-TATE PET/CT 
imaging for NENs. 
• 
Proportion of [68Ga]Ga-DOTA-TATE positive 
participants (TP participants) among CIM 
positive participants (TP or FN participants). 
• 
To evaluate the subject-level specificity 
of [68Ga]Ga-DOTA-TATE PET/CT 
imaging for NENs. 
• 
Proportion of [68Ga]Ga-DOTA-TATE negative 
participants (TN participants) among CIM 
negative participants (TN or FP participants). 
Secondary objective(s) 
Endpoint(s) for secondary objective(s) 
• 
To evaluate subject-level positive 
predictive values (PPV) of [68Ga]Ga-
DOTA-TATE PET/CT imaging. 
• 
Proportion of participants who are positive on 
both [68Ga]Ga-DOTA-TATE PET/CT imagings 
and CIM (TP participants) among participants 
who are positive on [68Ga]Ga-DOTA-TATE 
PET/CT imaging (TP or FP participants). 
• 
To evaluate subject-level negative 
predictive values (NPV) of [68Ga]Ga-
DOTA-TATE PET/CT imaging. 
• 
Proportion of participants who are negative on 
both [68Ga]Ga-DOTA-TATE PET/CT imaging and 
CIM (TN participants) among participants who 
are negative on [68Ga]Ga-DOTA-TATE PET/CT 
imaging (TN or FN participants). 
• 
To evaluate subject-level accuracy of 
[68Ga]Ga-DOTA-TATE PET/CT imaging. 
• 
Proportion of participants who have consistent 
results (i.e. TP or TN participants) among all 
participants assessed by [68Ga]Ga-DOTA-TATE 
PET/CT imaging and CIM. 

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Objective(s) 
Endpoint(s) 
• 
To evaluate region-level sensitivity of 
[68Ga]Ga-DOTA-TATE PET/CT imaging 
for NENs. 
• 
Proportion of [68Ga]Ga-DOTA-TATE positive 
regions (TP regions) among CIM positive regions 
(TP or FN regions). 
• 
To evaluate region-level specificity of 
[68Ga]Ga-DOTA-TATE PET/CT imaging 
for NENs. 
• 
Proportion of [68Ga]Ga-DOTA-TATE negative 
regions (TN regions) among CIM negative 
regions (TN or FP regions). 
• 
To evaluate region-level positive 
predictive values (PPV) of [68Ga]Ga-
DOTA-TATE PET/CT imaging. 
• 
Proportion of regions which are positive on both 
[68Ga]Ga-DOTA-TATE PET/CT imaging and CIM 
(TP regions) among regions which are positive 
on [68Ga]Ga-DOTA-TATE PET/CT imaging (TP 
or FP regions). 
• 
To evaluate region-level negative 
predictive values (NPV) of [68Ga]Ga-
DOTA-TATE PET/CT imaging. 
• 
Proportion of regions who are negative on both 
[68Ga]Ga-DOTA-TATE PET/CT imaging and CIM 
(TN regions) among regions which are negative 
on [68Ga]Ga-DOTA-TATE PET/CT imaging (TN 
or FN regions). 
• 
To evaluate region-level accuracy of 
[68Ga]Ga-DOTA-TATE PET/CT imaging. 
• 
Proportion of regions which have consistent 
results (i.e. TP or TN regions) among all regions 
assessed by [68Ga]Ga-DOTA-TATE PET/CT 
imaging and CIM. 
• 
To evaluate number of lesions detected 
by [68Ga]Ga-DOTA-TATE PET/CT 
imaging and each CIM at region-level. 
• 
Number of lesions detected by [68Ga]Ga-DOTA-
TATE PET/CT imaging and each CIM at region-
level. 
• 
To evaluate the impact of [68Ga]Ga-
DOTA-TATE PET/CT imaging on 
treatment decision. 
• 
Percentage of patients who underwent a change 
in intended treatment plan attributed to the 
[68Ga]Ga-DOTA-TATE PET/CT imagings as 
assessed by pre and post imaging 
questionnaires. 
• 
To evaluate inter-reader variability. 
• 
Inter-reader agreement on [68Ga]Ga-DOTA-
TATE PET/CT imaging. 
• 
To evaluate safety and tolerability of 
[68Ga]Ga-DOTA-TATE. 
• 
Incidence of Treatment emergent adverse event 
(TEAE) within 8 days after [68Ga]Ga-DOTA-
TATE administration. 
• 
To evaluate PK of [68Ga]Ga-DOTA-
TATE. 
• 
Pharmacokinetic parameters (AUCinf, AUClast, 
Cmax, Tmax, T1/2, CL, Vz etc.). 
• 
To evaluate lesion-level concordance 
for SSTR between [68Ga]Ga-DOTA-
TATE PET/CT imaging local read and 
local histopathology results. 
• 
Lesion-level concordance rate for SSTR between 
[68Ga]Ga-DOTA-TATE PET/CT imaging local 
read and local histopathology result among 
lesions that local histopathology result are 
available. 

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3.1 
Primary estimands 
The primary clinical question of interest is: What is the probability that [68Ga]Ga-DOTA-TATE 
PET/CT imaging truly detects tumor lesion(s) in subject-level for NENs using CIM (including 
[111In]In-Pentetreotide SPECT/CT and High Resolution CT with contrast (or MRI if CT with 
contrast is medically contraindicated) as standard of truth). 
The justification for the primary estimand is that it will capture the diagnostic performance of 
[68Ga]Ga-DOTA-TATE PET/CT imaging in detecting tumor lesion(s) in NENs subjects. For 
this reason, participants with confirmed or suspected NENs will be investigated with CIM 
obtained on or before screening phase (HVs will be categorized as CIM negative without 
performing CIM ) and confirmed or suspected NENs and HVs will be investigated 
with [68Ga]Ga-DOTA-TATE PET/CT imaging on treatment phase, and the results of [68Ga]Ga-
DOTA-TATE PET/CT imaging will be compared against the results of CIM as standard of truth. 
The primary estimands are described by the following attributes: 
Primary estimand 1: 
1. Population: Patients who show at least one lesion based on CIM by central read, received 
[68Ga]Ga-DOTA-TATE, completed a PET/CT scan and had a central read of the 
[68Ga]Ga-DOTA-TATE PET/CT imaging. 
2. Variable: The result of [68Ga]Ga-DOTA-TATE PET/CT imaging (positive (i.e., showing 
at least one lesion) or negative (i.e., not showing any lesion)). In the population above, a 
participant with positive [68Ga]Ga-DOTA-TATE PET/CT imaging corresponds to True 
positive (TP) and a participant with negative on [68Ga]Ga-DOTA-TATE PET/CT imaging 
corresponds to False negative (FN). 
3. Treatment of interest: [68Ga]Ga-DOTA-TATE injected as a single intravenous dose of 2 
MBq/kg (0.054 mCi/kg) of body weight up to a maximum total dose of 200 MBq (5.4 
mCi). 
4. Intercurrent events: None 
5. Summary measure: Estimate of proportion of participants who test positive on [68Ga]Ga-
DOTA-TATE PET/CT imaging (TP) among those who are CIM positive (TP+FN 

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according to [68Ga]Ga-DOTA-TATE PET/CT imaging) (subject-level sensitivity), along 
with 95% confidence interval. 
Primary estimand 2: 
1. Population: Participants who do not show any lesions based on CIM by central read or are 
HVs, received [68Ga]Ga-DOTA-TATE, completed a PET/CT imaging and had a central 
read of the [68Ga]Ga-DOTA-TATE PET/CT imaging. The population selection depends 
on the results of central read, therefore patients with NENs can be included if applicable, 
in addition to HVs who will be categorized as CIM negative without performing CIM. 
2. Variables: The result of [68Ga]Ga-DOTA-TATE PET/CT imaging (positive or negative). 
In the population above, a participant who test  positive on [68Ga]Ga-DOTA-TATE 
PET/CT imaging corresponds to False positive (FP) and a participant who test negative on 
[68Ga]Ga-DOTA-TATE PET/CT imaging corresponds to True negative (TN). 
3. Treatment of interest: [68Ga]Ga-DOTA-TATE injected as a single intravenous dose of 2 
MBq/kg (0.054 mCi/kg) of body weight up to a maximum total dose of 200 MBq (5.4 
mCi). 
4. Intercurrent events: None. 
5. Summary measure: Estimate of proportion of participants who test negative on [68Ga]Ga-
DOTA-TATE PET/CT imaging (TN) among those who are CIM negative (TN+FP 
according to [68Ga]Ga-DOTA-TATE PET/CT imaging) (subject-level specificity), along 
with 95% confidence interval. 
3.2 
Secondary estimands 
Not applicable. 
4 
Study design 
4.1 
Overall design 
Refer to Section 1.2 Schema for study design figure. 
This prospective, open-label, multi-center, single arm, phase III study, will enroll 
approximately 47 adult male or female participants with NENs and 23 HVs. Of all the 
participants with NENs, the number of participants with suspected NENs is limited to up to 5 
with negative CIM by central read in order to enroll sufficient number of participants with 
positive result in CIM. Negative CIM by central read is applicable for patients who do not show 
any lesions based on CIM by central read. All eligible participants will undergo [68Ga]Ga-
DOTA-TATE PET/CT imaging. [68Ga]Ga-DOTA-TATE will be administered intravenously at 
a single dose of 2 MBq/kg (0.054 mCi/kg) of body weight up to a maximum total dose of 200 
MBq (5.4 mCi), and imaging will be acquired 40 to 90 minutes after the intravenous injection 
of [68Ga]Ga-DOTA-TATE. 
The purpose of this study is to evaluate the diagnostic performance of [68Ga]Ga-DOTA-TATE 
PET/CT imaging compared with the CIM as standard of truth in patients with NENs and HVs. 
The data from this study will provide the evidence for diagnosis use of [68Ga]Ga-DOTA-TATE 
PET/CT imaging in patient with NENs in Japan. 

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Screening 
Participants must sign an informed consent form (ICF) prior to any study specific screening 
evaluations. All screening procedures must be completed within 35 days prior to Imaging day. 
All procedures described in the Assessment Schedule Table 1-2 must be carried out to confirm 
the eligibility. 
Enrollment 
Until Imaging day in the Treatment period, all participants will be assessed for eligibility. 
Enrollment will take place when all eligibility requirements described in the Assessment 
Schedule Table 1-2 are confirmed, prior to Imaging day in the Treatment period. After the 
registration, the tests which are defined in the Table 1-2 as pre-injection should be performed. 
To calculate the volume of the medication, the weight should be measured. All enrolled 
participants will be administered intravenously at a dose of 2 MBq/kg (0.054 mCi/kg) of body 
weight up to a maximum total dose of 200 MBq (5.4 mCi). And after 40-90 minutes from the 
injection, the participants will undergo [68Ga]Ga-DOTA-TATE PET/CT imaging. This visit 
should be completed within one day. 
Post-Treatment Follow-Up 
After the injection of [68Ga]Ga-DOTA-TATE, all participants will be followed for safety with 
a post imaging follow-up visit (Day 8 +/- 1 day). 
A participant may choose to discontinue follow-up components of the study at any time. 
4.2 
Scientific rationale for study design 
The design of this imaging study was chosen to evaluate diagnostic performance 
(subject/region-level sensitivity, specificity, PPV, NPV, accuracy) of [68Ga]Ga-DOTA-TATE 
PET/CT imaging compared with CIM as standard of truth (SoT). 
[111In]In-Pentetreotide has sufficient diagnostic capability for NENs. Subject-level sensitivity 
in patients with at least one positive lesions identified by CIM such as CT or MRI and with no 
positive lesions identified by CIM was 73.7-100% and  66.7-100%, respectively. In addition, 
[111In]In-Pentetreotide imaging has high concordance with the octreotide suppression test and 
immunohistological examination of SSTR (Review Report for OctreoScan I.V. Injection Set). 
Patients with NENs are often diagnosed with metastases, and it's not ethically and medically 
feasible to obtain biopsy sample from all lesions for histopahological confirmation. Given 
[111In]In-Pentetreotide imaging as well as CT and/or MRI are established diagnostic procedure 
for SSTR positive NENs, these CIM read can be used as SoT to evaluate diagnostic performance 
of [68Ga]Ga-DOTA-TATE PET/CT imaging. 
CIM for patients with NENs must include [111In]In-Pentetreotide SPECT or SPECT/CT and 
High Resolution CT with contrast (or MRI if CT with contrast is medically contraindicated). A 
centralized reading of CIM for NENs patient will be submitted to a designated CRO. An 
independent reader who will be blinded to  patient data (including clinical condition, 
histopathology and [68Ga]Ga-DOTA-TATE PET/CT imaging results). This central read result 
of CIM will be SoT and HVs will be categorized as CIM negative without performing CIM. 

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[68Ga]Ga-DOTA-TATE PET/CT imaging will be performed for all participants including HVs 
and PET/CT imaging will be submitted to a designated CRO for independent central read. 3 
independent readers, who will be blinded to patient data (including clinical condition, 
histopathology and CIM results) will read PET/CT imaging. Central read results will not be 
provided to the treating physician/Clinical Study Investigator. 
 
4.3 
Justification for dose 
[68Ga]Ga-DOTA-TATE will be administered intravenously at a dose of 2 MBq/kg (0.054 
mCi/kg) of body weight up to a maximum total dose of 200 MBq (5.4 mCi), and imaging will 
be acquired 40 to 90 minutes after the intravenous injection of [68Ga]Ga-DOTA-TATE. 
The pharmacokinetics of [68Ga]Ga-DOTA-TATE in blood has not been assessed. 
Estimated radiation absorbed dose per injected activity for organs and tissues of adult patients 
following an intravenous injection of [68Ga]Ga-DOTA-TATE were derived from different 
sources from literature (Sandström et al 2013; Josefsson et al 2018). The absorbed doses for the 
tissues with higher absorbed dose per unit activities (adrenals, kidney, liver, gall bladder wall, 
urinary bladder wall, pituitary gland) are those reported by Josefsson (2018), obtained using 
updated and more formalized methodologies based on ICRP 110 reference voxel phantoms. For 
the other tissues, the estimated absorbed doses are those reported by Sandstrom (2013), which 
were obtained using standard phantom-based dosimetry (Stabin 2006). 
Estimated radiation effective dose per injected activity for adult and pediatric patients following 
an intravenous injection of [68Ga]Ga-DOTA-TATE were calculated starting from available 
[68Ga]Ga-DOTA-TATE biokinetics data for adults (Sandström et al 2013), using Cristy-
Eckerman age-dependent phantoms provided by OLINDA/EXM software. The effective 
radiation dose resulting from the administration of 150 MBq (4.05 mCi) (within the range of 
the recommended [68Ga]Ga-DOTA-TATE injection dose) to adult weighing 75 kg, is about 
3.45 mSv. For an administered activity of 150 MBq (4.05 mCi) the typical radiation absorbed 
dose to the critical organs, which are the urinary bladder wall, the spleen and the 
kidneys/adrenals, are about 6, 37.5, 21 and 16.5 mGy, respectively. Because the spleen has one 
of the highest physiological uptakes, higher uptake and radiation dose to other organs or 
pathologic tissues may occur in patients with splenectomy. 
SNMMI Procedure Standard/EANM Practice Guideline (Hope et al 2023), which take into 
account the Directive 97/43/EURATOM (Council Directive 97/43/Euratom), recommends a 
dose range of 100-200 MBq of [68Ga]Ga-somatostatin analogue depending on patient’s weight. 
Thus, the recommended dosage of 2 MBq/kg for [68Ga]Ga-DOTA-TATE is in line with 
international guidelines and found to be an acceptable dose to have adequate performance and 
safety. In addition, [68Ga]Ga-DOTA-TATE dose of 2 MBq/kg appears to give a considerably 
lower total radiation dose to the patients as compared to [111In]In-Pentetreotide. For instance, 
the effective dose for  [68Ga]Ga-DOTA-TATE dose of 150 MBq to an adult weighing 75 kg 
was estimated to be approximately 3.15 mSv, while the effective dose for [111In]In-
Pentetreotide dose of 111 MBq was estimated to be 13 mSv. Numerous publications and post-
marketing experience have consistently demonstrates that imaging with [68Ga]Ga-DOTA-
TATE at this dose range is well tolerated. 

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The effect of radiation would be minimal for microdose nature of [68Ga]Ga-DOTA-TATE and 
it not be variable between patients and HVs. As the diagnostic performance of [68Ga]Ga-DOTA-
TATE PET/CT imaging should be evaluated in HVs for specificity assessment at same dose 
level with dosing to patients, this recommended dose of [68Ga]Ga-DOTA-TATE for patients is 
applicable for HVs. 
4.4 
Rationale for choice of control drugs (comparator/placebo) or 
combination drugs 
Not applicable 
4.5 
Rationale for public health emergency mitigation procedures 
During a public health emergency as declared by local or regional authorities e.g., pandemic, 
epidemic, or natural disaster, mitigation procedures to ensure participant safety and trial 
integrity may be implemented. Notification of the public health emergency as declared by local 
or regional authorities should be discussed among investigators and Novartis. All procedures 
adapted to the situation must be submitted, if required as per local regulations, through a 
protocol amendment for approval by local or regional Health Authorities and Ethics 
Committees prior to implementation of mitigation procedures. 
4.6 
Purpose and timing of interim analyses/design adaptations 
Not applicable 
4.7 
End of study definition 
Study completion is defined as when the last participant finishes their last study visit and any 
repeat assessments associated with this visit have been documented and followed-up 
appropriately by the Investigator. 
5 
Study population 
The study population will consist of approximately 47 eligible female or male adult participants 
with confirmed or suspected NENs, and 23 HVs. The number of participants with suspected 
NENs is limited to up to 5 with negative CIM by central read. 
 
5.1 
Inclusion criteria 
Participants eligible for inclusion in this study must meet all of the following criteria: 
1. Signed informed consent must be obtained prior to participation in the study 
2. Participants must be adults ≥ 18 years of age 
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 
4. For patient with NENs only: Participants with confirmed NENs based on histopathology, 
imaging and other relevant examination, or with suspected NENs which localization 
cannot be confirmed by conventional imaging 

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5. For HVs only: Male or female participant in good health condition as determined by no 
clinically significant findings from medical history, physical examination, vital signs, lab 
test and ECG 
6. Women of childbearing potential must have a negative urine or blood pregnancy test. 
5.2 
Exclusion criteria 
Participants meeting any of the following criteria are not eligible for inclusion in this study. 
1. Any additional medical condition, serious intercurrent illness, concomitant cancer or other 
extenuating circumstance that, in the opinion of the Investigator, would indicate a 
significant risk to safety or impair study participation. 
2. Inability to complete the needed investigational and conventional imaging due to any 
reason (severe claustrophobia, inability to lie still for the entire imaging time, etc.) 
3. Known allergy, hypersensitivity, or intolerance to [68Ga]Ga-DOTA-TATE and [111In]In-
Pentetreotide 
4. Therapeutic use of any somatostatin analogue except for the following washout period 
• Short-acting analogs of somatostatin can be used up to 24 hours before injection with 
[68Ga]Ga-DOTA-TATE 
• Long-acting analogs of somatostatin can be used up to 28 days before injection 
of [68Ga]Ga-DOTA-TATE  
5. Prior administration of a radiopharmaceutical unless 10 or more half-lives have elapsed 
before injection of [68Ga]Ga-DOTA-TATE 
6. Use of other investigational drugs within 30 days before screening 
7. Participants who are pregnant. 
8. Participants who are lactating. 
5.3 
Screen failures 
A screen failure occurs when a participant who consents to participate in the clinical study is 
subsequently found to be ineligible and therefore not entered in the study. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any serious adverse event 
(SAE). 
Participants who sign an informed consent form and subsequently found to be ineligible will be 
considered a screen failure. The reason for screen failure should be entered on the applicable 
eCRF. The demographic information, informed consent, Visit Date, subject Status at Screening, 
Inclusion/Exclusion, Assignment, Withdrawal of Informed Consent (if applicable), Death (if 
applicable) and Screening Phase Disposition pages must also be completed for screen failure 
participants. No other data will be entered into the clinical database for participants who are 
screen failures, unless the participant experienced a serious adverse event during the screening 
period (see SAE section for reporting details). Data and samples collected from participants 
prior to screen failure may still be analyzed. 

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Participants who sign an informed consent and are considered eligible but fail to be started on 
treatment for any reason will be considered an early terminator. The reason for early termination 
should be captured on the appropriate disposition eCRF. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Each case must be discussed and agreed with Novartis, Eckert & Ziegler 
Radiopharma GmbH on a case-by-case basis. 
Re-screening is only allowed once. There is no restriction on how much time must pass from 
the date of screen failure to the date of re-screening. 
If a participant re-screens for the study, then they must sign a new ICF. The 
investigator/qualified site staff will record if the participant was re-screened on the re-screening 
eCRF and any applicable screening numbers the participant was issued prior to the current 
screening number. 
The date of the new informed consent signature must be entered on the informed consent eCRF 
to correspond to the new screening subject number. For re-screening, all screening assessments 
must be performed per protocol. 
5.3.1 
Replacement policy 
Participants will not be replaced. 
5.3.2 
Participant numbering 
Upon signing the informed consent form, the participant is assigned to the next sequential 
Participant Number (No.) available. The Participant No. consists of the Site Number (Site No.) 
(as assigned by Novartis to the investigative site) with a sequential number suffixed to it, so 
that each participant is numbered uniquely across the entire database. This number will be 
retained throughout participation in the trial. If the participant is rescreened, then a new 
Participant No. will be assigned. 
6 
Study treatment(s) and concomitant therapy 
6.1 
Study treatment(s) 
In this study, the term “study treatment” used in the protocol refers to the investigational 
radioligand imaging compound [68Ga]Ga-DOTA-TATE, which after radiolabeling with 68Ga, 
serves as a radioactive PET diagnostic agent for localization of SSTR-positive tumors, and to 
the 68Ge/68Ga generator used to obtain 68Ga as a 68Ga chloride solution. Both study treatments 
have no therapeutic effect. 
Due to short radioactive half-life of 68Ga, [68Ga]Ga-DOTA-TATE cannot be supplied as ready-
to-use radiopharmaceutical. Therefore, [68Ga]Ga-DOTA-TATE will be manufactured directly 
at clinical trial sites immediately prior to administration into participants by chelation of 68Ga 
with DOTA-TATE supplied as a cold kit for the radiopharmaceutical preparation. The 68Ga 
used for chelation will be eluted from the 68Ge/68Ga generator as 68Ga chloride. [68Ga]Ga-
DOTA-TATE will be prepared as a sterile solution. 

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 [68Ga]Ga-DOTA-TATE will be administered intravenously at a dose of 2 MBq/kg (0.054 
mCi/kg) of body weight up to a total maximum dose of 200 MBq (5.4 mCi) (refer 
to Section 6.2 for details on handling, preparation and administration). 
[68Ga]Ga-DOTA-TATE used for PET imaging must be prepared only with the use of DOTA-
TATE cold kit for the radiopharmaceutical preparation and the 68Ge/68Ga generator. 
Sponsors or their designee will provide 68Ge/68Ga generator and DOTA-TATE cold kit for the 
radiopharmaceutical preparation of [68Ga]Ga-DOTA-TATE. 
Table 6-1 
Investigational and control drug 
Treatment Title 
DOTA-TATE 
68Ge/68Ga Generator 
Type 
drug 
drug 
Dose Formulation 
Kit for radiopharmaceutical 
preparation 
Radionuclide generator 
Unit Dose 
Strength(s) 
40 mcg per kit 
1850 MBq (50 mCi) 
Dosage Level(s) 
 [68Ga]Ga-DOTA-TATE will be 
administered at a dose of 2 
MBq/kg (0.054 mCi/kg) of body 
weight up to a maximum total 
dose of 200 MBq (5.4 mCi) 
 NA 
Route of 
Administration 
Intravenous use 
(After radiolabeling with Ga-68) 
NA 
Use 
experimental 
experimental 
IMP 
Yes ([68Ga]Ga-DOTA-TATE, 
after radiolabeling with Ga-68) 
Yes, Radionuclide generator 
Sourcing 
Provided centrally by the 
sponsor (global) 
Provided centrally by the 
sponsor (global) 
Packaging and Labeling 
Study treatment will be 
provided as a kit. Each kit will 
be labeled as required per 
country requirement. 
The 68Ge/68Ga Generator is 
presented as a stainless-steel 
case 
6.1.1 
Additional study treatments 
No other treatment beyond investigational drug and control drug are included in this trial. 
6.1.2 
Treatment arms/group 
Not applicable for this study because there is only one treatment arm. 
6.1.3 
Guidelines for continuation of treatment 
Not applicable for this study. 
6.1.4 
Treatment duration 
[68Ga]Ga-DOTA-TATE will be administered intravenously at a dose of 2 MBq/kg (0.054 
mCi/kg) of body weight up to a maximum total dose of 200 MBq (5.4 mCi) at the imaging day. 

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6.1.4.1 
Treatment beyond disease progression 
Not applicable. 
6.1.5 
Medical devices 
Not applicable. 
6.2 
Preparation, handling, storage, and accountability 
Each study site will be supplied with study treatment in packaging as described under Table 6-
1 Investigational and control drugs section. 
The DOTA-TATE as a sterile two-vials kit and the 68Ge/68Ga Generator will be supplied by 
Sponsors to hospital's radiopharmacies. The elution of the 68Ge/68Ga Generator and the 
reconstitution of the kit with the eluate for radiolabeling will be performed at clinical trial sites. 
[68Ga]Ga-DOTA-TATE must be prepared and administered by qualified/authorized personnel 
only in accordance with pharmaceutical quality requirements and radiation safety regulations. 
After reconstitution, [68Ga]Ga-DOTA-TATE solution will be administered by intravenous 
injection. 
The instructions and explanations for ordering, delivery, elution of the 68Ge/68Ga Generator, 
radiolabeling procedure and dispensing of [68Ga]Ga-DOTA-TATE, as well as cautionary notes, 
analytical controls and stability information for the radiolabeled product will be provided to 
each site (please refer to the Pharmacy Manual). 
6.2.1 
Handling of study treatment 
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secured location to which only the Investigator and designated 
site personnel have access. Upon receipt, all study treatment must be stored according to the 
instructions specified in the Investigator's Brochure. 
Clinical supplies are to be dispensed only in accordance with the protocol. 
Medication labels will be in the local language and comply with the legal requirements. They 
will include storage conditions for the study treatment but no information about the participant. 
The Investigator or designated site staff must maintain an accurate record of the shipment and 
dispensing of study treatment in a drug accountability log. Monitoring of drug accountability 
will be performed by field monitors during site or remote monitoring visits, and at the 
completion of the trial. It must be possible to reconcile delivery records with those of used and 
unused medication. Any discrepancies must be accounted for and explained. Appropriate forms 
of deliveries and returns must be signed and dated by the responsible person at the clinical site 
and maintained as records. The return or disposal of all study medication will be documented 
appropriately. 
For more details about technical complaints, the handling of [68Ga]Ga-DOTA-TATE refer to 
the Pharmacy Manual. 

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6.2.2 
Handling of other treatment 
Not applicable. 
6.2.3 
Instruction for prescribing and taking study treatment 
For further details on the [68Ga]Ga-DOTA-TATE administration refer to Section 6.1 and to 
Pharmacy Manual. 
6.3 
Measures to minimize bias: randomization and blinding 
6.3.1 
Treatment assignment, randomization 
Not applicable. 
6.3.2 
Treatment blinding 
The following blinding is applicable in this study: 
• [68Ga]Ga-DOTA-TATE PET/CT imaging will be submitted to a CRO for independent 
centralized read by 3 independent readers blinded to CIM and patient data collected in 
clinical database. 
• CIM will be submitted to a CRO for independent centralized read by 1 independent 
reader, blinded to [68Ga]Ga-DOTA-TATE PET/CT imaging and patient data collected in 
clinical database. 
6.3.3 
Emergency breaking of assigned treatment code 
Not applicable. 
6.4 
Study treatment compliance 
All participants will have the study treatment administered during site visits on imaging day. 
All study treatments must be recorded in the Drug Accountability Log and in the corresponding 
eCRF pages. 
6.5 
Dose modification 
Dose modifications are not applicable in this study for the investigational imaging agent which 
is administered intravenously as a single dose. 
6.5.1 
Definitions of dose limiting toxicities (DLTs) 
Not applicable. 
6.5.2 
Dose modifications 
Not applicable. 
6.5.3 
Follow-up for toxicities 
Not applicable. 

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6.5.3.1 
Follow up on potential drug-induced liver injury (DILI) cases 
Not applicable. 
6.6 
Continued access to study treatment after the end of the study 
Not applicable. 
6.6.1 
Post trial access 
Not applicable. 
6.7 
Treatment of overdose 
In the event of administration of a radiation overdose with investigational agent, the radiation 
absorbed dose to the participant should be reduced where possible by increasing the elimination 
of the radionuclide from the body by frequent micturition or by forced diuresis and frequent 
bladder voiding. It might be helpful to estimate the effective radiation dose that was applied. 
In the event of an overdose, the Investigator/treating physician should: 
• Contact the medical monitor immediately. 
• Document the quantity of the excess dose as well as the duration of the overdose. 
• Follow standard clinical practice for overdose of diagnostic radiopharmaceuticals. 
6.7.1 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, participant or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal product, 
which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded on 
the appropriate CRF irrespective of whether or not associated with an AE/SAE. Study treatment 
errors and uses outside of what is foreseen in the protocol, misuse or abuse will be collected 
and reported in the safety database irrespective of it being associated with an AE/SAE within 
24 hours of Investigator’s awareness. For more information on AE and SAE definition and 
reporting requirements, please see the respective sections. 
6.8 
Concomitant and other therapy 
• Use of diuretics (e.g. furosemide) to help the subject voiding before PET/CT acquisition is 
allowed in case of need, upon the discretion of the Investigator, and should be captured in 
the eCRF like other concomitant medications. 

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6.8.1 
Concomitant therapy 
All medications, procedures, and significant non-drug therapies (including physical therapy and 
blood transfusions) administered after the participant was enrolled into the study must be 
recorded on the appropriate eCRF. 
Each concomitant drug must be individually assessed against all exclusion criteria and 
prohibited medication. If in doubt, the Investigator should contact the Novartis, Eckert & 
Ziegler Radiopharma GmbH medical monitor before enrolling a participant or allowing a new 
medication to be started. If the participant is already enrolled, contact Novartis, Eckert & 
Ziegler Radiopharma GmbH to determine if the participant should continue participation in the 
study. 
Use of diuretics (e.g. furosemide) to help participants voiding before PET/CT acquisition is 
allowed in case of need, upon the discretion of the Investigator. 
6.8.1.1 
Permitted concomitant therapy requiring caution and/or action 
Some evidence exists that corticosteroids can induce down-regulation of SSTR2. Repeated 
administration of high-doses of corticosteroids prior to [68Ga]Ga-DOTA-TATE administration 
may cause insufficient SSTR2 expression for adequate visualization of SSTR-positive tumors. 
6.8.1.2 
Use of bone modifying agents 
Not applicable. 
6.8.2 
Prohibited medication 
HV participants 
Except for protocol allowed concomitant medication and/or any medication which may be 
required to treat adverse events [and permitted oral or injectable contraceptives for female 
participants], no medication other than study treatment will be allowed from the date participant 
signs the inform consent until all of the study completion evaluations have been performed. 
NENs patients 
Somatostatin analogues competitively bind to the same SSTR as [68Ga]Ga-DOTA-TATE. Refer 
to Section 5.2 for washout period prior to [68Ga]Ga-DOTA-TATE imagings. 
7 
Discontinuation of study treatment and participant 
discontinuation/withdrawal 
7.1 
Discontinuation of study treatment 
Since [68Ga]Ga-DOTA-TATE is administered as a single intravenous injection, discontinuation 
of [68Ga]Ga-DOTA-TATE is not applicable. 
7.2 
Participant discontinuation from the study 
Discontinuation from study is when the participant permanently stops receiving the study 
treatment, and further protocol-required assessments or follow-up, for any reason. 

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If the participant agrees, a final evaluation at the time of the participant’s study discontinuation 
should be made as detailed in Section 1.3 Schedule of Activities. 
7.3 
Withdrawal of informed consent and exercise of participants’ 
data privacy rights 
Withdrawal of consent/opposition to use of data and/or biological samples occurs when a 
participant: 
• Explicitly requests to stop use of their data 
and 
• No longer wishes to receive study treatment 
and 
• Does not want any further visits or assessments (including further study-related contacts) 
This request should be made as per local regulations (e.g. in writing) and recorded in the source 
documentation. 
Withdrawal of consent impacts ability to further contact the participant, collect follow-up data 
(e.g. to respond to data queries) and potentially other country-specific restrictions. It is therefore 
very important to ensure accurate recording of withdrawal vs. discontinuation based on the 
protocol definitions of these terms. 
In this situation, the Investigator should make a reasonable effort (e.g. telephone, e-mail, letter) 
to understand the primary reason for the participant’s decision to withdraw their 
consent/exercise data privacy rights and record this information. The Investigator shall clearly 
document if the participant has withdrawn his/her consent for the use of data in addition to a 
study discontinuation. 
Study treatment must be discontinued and no further assessments conducted. 
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up. 
If the participant agrees, a final evaluation at the time of the participant’s withdrawal of 
consent/exercise data privacy rights should be made as detailed in Section 1.3 Schedule of 
Activities. 
Further details on withdrawal of consent or the exercise of participants' data privacy rights are 
included in the corresponding informed consent form. 
7.4 
Lost to follow-up 
For participants whose status is unclear because they fail to appear for study visits or fail to 
respond to any site attempts to contact them without stating an intention to discontinue from 
study treatment or discontinue, the Investigator must document "due diligence" steps taken to 
contact the participant, e.g. dates of telephone calls, registered letters in the source documents. 
A participant should not be considered as lost to follow-up until due diligence has been 
completed or until the end of the study. 

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7.5 
Early study termination by the Sponsor 
The study can be terminated by Novartis, Eckert & Ziegler Radiopharma GmbH at any time. 
Reasons for early termination (but not limited to) 
• Unexpected, significant, or unacceptable safety risk to participants enrolled in the study 
• Decision based on recommendations from applicable board(s) after review of safety and 
efficacy data 
• Discontinuation of study treatment development in this indication 
In taking the decision to terminate, Novartis, Eckert & Ziegler Radiopharma GmbH will always 
consider participant welfare and safety. Should early termination be necessary, participants 
must be seen as soon as possible and treated as a participant who discontinued from study 
treatment (e.g. safety follow up period must be completed if applicable with required visits to 
be performed). The Investigator may be informed of additional procedures to be followed in 
order to ensure that adequate consideration is given to the protection of the participant’s 
interests. The Investigator or Novartis, Eckert & Ziegler Radiopharma GmbH depending on 
local regulation will be responsible for informing IRBs/IECs of the early termination of the trial. 
8 
Study Assessments and Procedures 
• Study procedures and their timing are summarized in Section 1.3 Schedule of Activities. 
Protocol waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with Novartis, Eckert & Ziegler 
Radiopharma GmbH upon occurrence or awareness to determine if the participant should 
continue or discontinue study treatment. 
• Adherence to the study design requirements, including those specified in Section 1.3 
Schedule of Activities, is essential and required for study conduct. 
• Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples. 
8.1 
Screening 
Screening 
Written informed consent must be obtained prior to any screening procedures. Please refer 
to Section 10.1.2 for the Informed Consent procedures. 
All screening assessments should occur within 35 days prior to imaging day. CIM assessment 
performed as a part of clinical practice within 2 months prior to imaging day even before 
informed consent, can be used as standard reference as long as imaging quality meets study 
defined criteria. Refer to Imaging Manual for details. 
It is permissible to re-screen (only once) a participant if he or she fails the initial screening 
(screen failure); however, each case must be discussed and agreed with the Sponsor on a case-
by-case basis. Re-screening should not be performed for avoiding the eligibility criteria, putting 
the participant at safety risk. Re-screened participants will need to be re-consented and a new 
Participant Number will be assigned. Re-screening tests should be repeated as per 

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inclusion/exclusion requirements and re-screening should be documented in the source 
documents. 
8.1.1 
Eligibility screening 
• For HVs: The investigator or his/her delegate will confirm that the participant fulfills all 
the inclusion/exclusion criteria 
For NEN patients: The Investigator or his/her delegate will contact the registration center after 
confirming that the participant fulfills all the inclusion/exclusion criteria. The registration center 
will confirm the result of CIM by central read and notify the registration to investigators. The 
registration center will limit the enrollment of patients with negative CIM up to 5. Details will 
be provided in the registration manual. 
8.2 
Participant demographics/other baseline characteristics 
Country-specific regulations should be considered for the collection of demographic and 
baseline characteristics in alignment with the eCRF. 
Participant demographics: age, sex, race/predominant ethnicity (if permitted) and relevant 
medical history/current medical conditions (until date of signature of informed consent) will be 
recorded in the eCRF. Where possible, the diagnosis and not symptoms should be recorded. 
Participant race/ethnicity data are collected and analyzed to identify any differences in the 
safety and/or efficacy profile of the treatment due to these characteristics. In addition, we will 
assess the diversity of the study population as required by Health Authorities. 
All prescription medications, over-the-counter drugs and significant non-drug therapies prior to 
the start of the study must be documented. See protocol Section 10.1.5 for further details on 
what information must be recorded on the appropriate page of the eCRF. 
Participant demographic and baseline characteristic data to be assessed on all participants 
include: 
• Demographic information: Age, Gender, Race and ethnicity 
• ECOG Performance status scale 
• Height and Weight 
• Vital signs: Body temperature, Blood pressure, Pulse rate, Respiratory rate measurements 
• 12 Lead ECG 
• Laboratory evaluations: Hematology, Chemistry, Urinalysis, Coagulation, and Pregnancy 
testing (if applicable) 
• Conventional Imaging (Patients with NENs only) 
• Patient Management Questionnaire (Patients with NENs only) 
• Adverse Events 
• Medical history: 
• Ongoing medical conditions, symptoms and diseases which are recorded on the 
Medical History eCRF should include the toxicity grade when applicable. 
• Concomitant medications of the last 30 days prior to imaging day 

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• Other important medical, surgical, and allergic conditions that could have an impact 
on the participant's evaluation, and current medical conditions (e.g. all relevant 
current medical conditions which are present at the time of signing informed consent). 
• Diagnosis and Extent of Cancer (if applicable for patients with NENs): Date of initial 
diagnosis, Date of the last relapse/progression, Extent of disease, Functional test, 
Histopathology result (Diagnosis of disease, Ki67 proliferation index, Histological grade, 
SSTR expression status). Any assessments after biopsy will be documented on the 
appropriate eCRF. 
• Prior Antineoplastic Medications/Radiotherapy/Surgery 
  
ECOG Performance status scale will be used as described in Table 8-1. 
Table 8-1 
ECOG performance status 
0 
Fully active, able to carry on all pre-disease 
performance without restriction 
1 
Restricted in physically strenuous activity but 
ambulatory and able to carry out work of a light 
or sedentary nature e.g., light house work, office 
work 
2 
Ambulatory and capable of all self-care but 
unable to carry out any work activities. Up and 
about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed 
or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any self-
care. Totally confined to bed or chair 
5 
Dead 
8.3 
Efficacy assessments 
Efficacy assessments in this study include diagnostic assessment of disease using CIM (NENs 
patients only) at screening as well as assessments of [68Ga]Ga-DOTA-TATE PET/CT imaging. 
In addition, disease assessment using histopathology will be collected for the participants whose 
histopathology assessment is available. Planned time points for all efficacy assessments are 
provided in Section 1.3 Schedule of Activities. 
8.3.1 
Imaging for tumor assessment 
The imaging assessment collection plan for this study is presented in Table 8-2. 
Table 8-2 
Imaging Assessment Collection Plan 
Imaging procedure 
Mandatory or Optional 
Imaging Acquisition Timing 
[111In]In-Pentetreotide 
SPECT/CT** 
Mandatory - NENs patients 
only 
screening* 
High Resolution CT with 
contrasts (or MRI if CT with 
contrast is medically 
Mandatory - NENs patients 
only 
screening* 

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Imaging procedure 
Mandatory or Optional 
Imaging Acquisition Timing 
contraindicated) of at least 
Chest, Abdomen and Pelvis 
(and any additional region as 
clinically indicated) 
[68Ga]Ga-DOTA-TATE PET/CT 
Mandatory - all participants 
Imaging day 
*CIM assessment performed as a part of clinical practice within 2 months prior to imaging day, even 
before informed consent, can be used as long as imaging quality meets study defined criteria. 
**If SPECT/CT is not available in the clinical site, SPECT can be acceptable. 
[68Ga]Ga-DOTA-TATE PET/CT imaging 
[68Ga]Ga-DOTA-TATE PET/CT imaging will be performed for all participants including HVs 
and PET/CT imaging will be submitted to the designated central CRO for independent central 
review. Three independent reviewers, who will be blinded to CIM and other patient data 
collected in clinical database will review PET/CT images. Central read results will not be 
provided to the treating physician/Clinical Study Investigator. If applicable for histopathology 
assessments detailed in Section 8.3.2, local read results of [68Ga]Ga-DOTA-TATE PET/CT 
imaging will be used for the assessment. 
 
CIM for NENs patient 
CIM for patients with NENs must include [111In]In-Pentetreotide SPECT/CT and High 
Resolution CT with intravenous and oral contrasts (or MRI if CT with contrast is medically 
contraindicated). A centralized reading of CIM for patients with NENs will be performed by a 
central independent reader who will be blinded to [68Ga]Ga-DOTA-TATE PET/CT imaging 
results and other patient data collected in clinical database. Further details will be provided in 
the Imaging Manual. 
8.3.2 
Histopathology assessments 
From prospective biopsy or surgery performed within 30 days after imaging day : In the cases 
where pathology will be available, histopathology assessments by the local pathologists, who 
are not blinded to [68Ga]Ga-DOTA-TATE PET/CT imaging results, CIM and other patient data 
collected in clinical database, will be performed as per standard clinical practice, and results are 
to be provided within 2 weeks of the biopsy or surgery. 
From retrospective biopsy performed before imaging day : In case if pathology is available, the 
result will be collected. 
Pathology data collected for histopathology assessments can be documented in eCRF (e.g. 
Diagnosis and Extent of Cancer). 
8.3.3 
Appropriateness of imaging assessments 
CIM including [111In]In-Pentetreotide SPECT/CT and High Resolution CT with contrasts (or 
MRI if CT with contrast is medically contraindicated) is considered as the SoT to assess the 
diagnostic performance of [68Ga]Ga-DOTA-TATE PET/CT imaging. CIM and [68Ga]Ga-
DOTA-TATE PET/CT imaging will be read by independent central reviewers, who will be 

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blinded to patient data (including clinical condition, histopathology and each other imaging 
result). 
Since patients with NENs are often metastatic at the time of diagnosis, it is ethically impossible 
to make a histological diagnosis by biopsy of all lesions, and since CIM including [111In]In-
Pentetreotide SPECT/CT and High Resolution CT with contrasts (or MRI if CT with contrast 
is medically contraindicated) have been established for SSTR-positive NENs, it is considered 
appropriate to evaluate the diagnostic performance of [68Ga]Ga-DOTA-TATE PET/CT imaging 
using CIM as the SoT. 
8.4 
Safety assessments 
Safety assessments are specified below with Section 1.3 Schedule of Activities detailing when 
each assessment is to be performed. 
For details on AE collection and reporting, refer to Section 8.6. 
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e. pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, regular 
phone or virtual calls can occur for safety monitoring and discussion of the participant´s health 
status until it is safe for the participant to visit the site again. 
8.4.1 
Physical examinations 
A complete physical examination will include the examination of general appearance, skin, 
neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, 
extremities, vascular, and neurological. If indicated based on medical history and/or symptoms, 
rectal, external genitalia, breast, and pelvic exams will be performed. 
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram (kg) in indoor clothing, 
but without shoes) will be measured as specified in Table 1-2. 
Information for all physical examinations must be included in the source documentation at the 
study site. Clinically relevant findings that are present prior to signing informed consent must 
be recorded on the appropriate eCRF that captures medical history. Significant findings made 
after signing informed consent which meet the definition of an adverse event must be recorded 
as an adverse event. 
8.4.2 
Vital signs 
Vital signs (body temperature, pulse rate, blood pressure (Systolic and diastolic), respiratory 
rate) will be monitored as per Section 1.3 Schedule of Activities. 

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8.4.3 
Electrocardiograms 
Figure 8-1 
Timing of study procedures 
 
Single local 12 lead ECGs are collected. 
ECGs will be locally collected and evaluated. Interpretation of the tracing must be made by a 
qualified physician and documented on the appropriate eCRF. ECG tracing should be labeled 
with the study number, participant initials (where regulations permit), participant number, date 
and time, and kept in the source documents at the study site. Clinically significant ECG 
abnormalities present at screening should be reported on the appropriate eCRF. Clinically 
significant findings must be discussed with Novartis prior enrolling the participant in the study. 
New or worsened clinically significant findings occurring after informed consent must be 
recorded as adverse events. 
The original ECG appropriately signed must be collected and archived at the study site. If heat 
sensitive paper is used, a certified copy on non-heat sensitive paper must be also collected and 
archived at the study site. 
Additional, unscheduled, safety ECGs may be repeated at the discretion of the Investigator at 
any time during the study as clinically indicated. 
Table 8-3 
Local ECG collection plan 
Week (or Cycle) 
Day 
Time 
Number of ECG 
Replicates 
Screening 
-35 to -1 
Screening 
12 Lead Single 
Imaging day 
1 
Post dose 2 hours 
12 Lead Single 
Unscheduled or Unplanned sample 
Anytime 
12 Lead Single 
8.4.3.1 
Cardiac imaging - MRA (magnetic resonance angiography), MUGA 
(multiple gated acquisition) scan or echocardiogram 
Not applicable. 
8.4.3.2 
Cardiac enzymes 
Not applicable. 

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8.4.4 
Clinical safety laboratory tests 
Local laboratory will be used for analysis of hematology, chemistry, urinalysis, coagulation, 
and pregnancy testing (if applicable) according to the schedule of assessments as described in 
Table 1-2. The samples need to be taken prior to the injection of the [68Ga]Ga-DOTA-TATE.  
Urine samples will be collected at screening, at imaging day and safety follow-up by dipstick 
and analyzed locally at the clinical site if dipstick results are abnormal. 
All abnormal lab results must be evaluated for criteria defining an adverse event and reported 
as such if the criteria are met. For those lab adverse events, repeated evaluations are mandatory 
until normalization of the result(s) or until the result is no longer considered to be clinically 
significant. 
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria: 1) they induce clinical signs or symptoms, 2) they are considered 
clinically significant, or 3) they require concomitant therapy or procedures. Clinically 
significant abnormal laboratory values or test results should be identified through a review of 
values outside of normal ranges/clinically notable ranges, significant changes from screening 
or the previous visit. 
At any time during the study, abnormal laboratory parameters which are clinically 
relevant, whether specifically requested in the protocol or not, will be recorded on the AE eCRF 
page. Laboratory data will be summarized using the Common Terminology Criteria for Adverse 
Events (CTCAE) version 5.0 (Section 10.3.1). Additional analyses are left to the discretion of 
the Investigator. 
Novartis must be provided with a copy of the local laboratory’s certification (if applicable), and 
a tabulation of the normal ranges and units of each parameter collected in the eCRF. Any 
changes regarding normal ranges and units for laboratory values assessed during the study must 
be reported via an updated tabulation indicating the date of revalidation.  
The Investigator is responsible for reviewing all laboratory reports for participants in the study 
and evaluating any abnormalities for clinical significance. 
Table 8-4 
Laboratory assessments 
Test Category 
Test Name 
Hematology 
Hematocrit, Hemoglobin, Mean Corpuscular 
Hemoglobin (MCH), Platelets, Erythrocytes, 
Leukocytes, Differential (Basophils, Eosinophils, 
Lymphocytes, Monocytes, Neutrophils (absolute 
value preferred, percentages are acceptable)) 
Chemistry 
Albumin, Alkaline phosphatase, Alanine 
Aminotransferase (ALT), Aspartate 
Aminotransferase (AST), Gamma-glutamyl 
transferase (GGT), Lactate dehydrogenase 
(LDH), Bicarbonate*, Calcium, Magnesium, 
Phosphate (inorganic phosphorus), Chloride, 
Sodium, Potassium, Creatinine, Creatine kinase 
(CK), Direct Bilirubin, Total Bilirubin, Blood Urea 

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Test Category 
Test Name 
Nitrogen (BUN) or Urea, Uric Acid, Amylase, 
Lipase, Plasma Glucose (fasting) 
Urinalysis 
Macroscopic Panel (Dipstick) (Color, Bilirubin, 
Blood, Glucose, Ketones, Leukocytes esterase, 
Nitrite, pH, Protein, Specific Gravity, 
Urobilinogen) 
If Dipstick is abnormal, Microscopic Panel (Red 
Blood Cells, White Blood Cells, Casts, Crystals, 
Bacteria, Epithelial cells) will be added (only 
needs to be recorded in the source 
documentation). 
Coagulation 
Prothrombin time (PT), International normalized 
ratio [INR]), Activated partial thromboplastin time 
(APTT) 
Pregnancy testing 
Serum / Urine pregnancy testing (refer to 
'Pregnancy testing' Section 8.4.5) 
*Total carbon dioxide or equivalent is acceptable for Bicarbonate 
8.4.5 
Pregnancy testing 
All women of childbearing potential will have pregnancy testing. Serum or urine pregnancy 
testing depending on Investigator's preference will be performed at screening visit. 
A woman is considered of childbearing potential from menarche until becoming post-
menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 
months without an alternative medical cause and an appropriate clinical profile. 
Permanent sterilization methods include hysterectomy, bilateral tubal ligation, bilateral 
salpingectomy and bilateral oophorectomy. In the case of oophorectomy alone, only when the 
reproductive status of the woman has been confirmed by follow-up hormone level assessment 
is she considered to be not of child-bearing potential. 
Medical documentation of permanent method of sterilization must be retained as source 
documents. 
In absence of the medical documentation confirming permanent sterilization, or if the post-
menopausal status is not clear, the Investigator should use his medical judgment to appropriately 
evaluate the fertility state of the woman and document it in the source document. 
8.4.6 
Suicidal ideation and behavior risk monitoring 
Not applicable. 
8.4.7 
Other safety evaluations 
Not applicable. 
8.4.8 
Appropriateness of safety measurements 
Not applicable. 

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8.5 
Additional assessments 
8.5.1 
Clinical Outcome Assessments (COAs) 
Not applicable. 
8.5.2 
Imaging 
Not applicable. 
8.5.3 
Other assessments 
Patient Management questionnaire (NENs patients only) will be completed by the treating 
physician/Clinical Study Investigator before and until Safety follow up after having the local 
read results of the [68Ga]Ga-DOTA-TATE PET/CT imaging (total 2 times). The results must 
be recorded on the appropriate eCRF. 
8.6 
Adverse events (AEs), serious adverse events (SAEs), and other 
safety reporting 
The Investigator and any qualified designees are responsible for managing the safety of 
individual participants. They are also responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and for following up all AEs and SAEs. 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures 
for 
completing 
and 
transmitting 
SAE 
reports 
are 
provided 
below 
(Section 8.6.1, Section 8.6.2, and Section 8.6.3). 
For the investigational product and for non-authorized AxMPs (when applicable), information 
about adverse drug reactions and how to manage them can be found in the Investigator's 
Brochure (IB) or equivalent documentation. Information about adverse drug reactions can also 
be found in the product information for marketed products. 
Novartis qualified medical personnel will be readily available to advise on trial-related medical 
questions or problems. 
8.6.1 
Adverse events 
Definition of AEs 
An adverse event (AE) is any untoward medical occurrence (e.g., any occurrence of unfavorable 
and unintended sign(s), symptom(s) or medical condition, including abnormal laboratory 
findings, or worsening of any pre-existing sign(s), symptom(s) or medical condition) in a 
participant after providing written informed consent for participation in the study. Therefore, 
an AE may or may not be temporally or causally associated with the use of any treatment used 
in this study. This includes events reported by the participant (or, when appropriate, by a 
caregiver, surrogate, or the participant’s legally authorized representative). 
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria: 
• they induce clinical signs or symptoms 

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• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values considered to be non-typical in participant with the 
underlying disease. 
Collecting and assessing AEs 
The occurrence of AEs must be sought by non-directive questioning of the participant at each 
visit during the study. AEs also may be detected when they are volunteered by the participant 
during or between visits or through physical examination findings, laboratory test findings, or 
other assessments. 
The investigator will attempt to establish a diagnosis of the event (including lab abnormalities 
that constitute AEs) based on signs, symptoms, and/or other clinical information. Whenever 
possible, the diagnosis (not the individual signs/symptoms) will be documented as the AE. 
For each AE, the investigator must assess: 
The Common Toxicity Criteria (CTC). 
AEs will be assessed and graded according to the Common Terminology Criteria for Adverse 
Events (CTCAE) version. 
The causality 
The investigator is obligated to assess the relationship between any treatment used in the study 
(study treatment) and each occurrence of each AE. The investigator will use clinical judgment 
to determine the relationship. A reasonable possibility of a relationship conveys that there are 
facts, evidence, and/or arguments to suggest a causal relationship, rather than a relationship 
cannot be ruled out. Alternative causes, such as underlying disease(s), concomitant therapy, and 
other risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 
If the event is due to lack of efficacy or progression of underlying illness (i.e. progression of 
the study indication) the assessment of causality will usually be ‘Not suspected.’ The rationale 
for this guidance is that the symptoms of a lack of efficacy or progression of underlying illness 
are not caused by the trial drug, they happen in spite of its administration and/or both lack of 
efficacy and progression of underlying disease can only be evaluated meaningfully by an 
analysis of cohorts, not on a single participant 
For causality assessment, the investigator will also consult the IB and/or product information, 
for marketed products. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
Handling of AEs 

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All adverse events must be treated appropriately. More information about how to manage AEs 
can be found in the IB. Information about adverse drug reactions can also be found in product 
information for marketed products. 
Once an AE is detected, the Investigator must pro-actively followed up the participant, until 
resolution of the AE, or until it is judged to be not recovered/not resolved (e.g., continuing at 
the end of the study), or until stabilization, or until the participant is lost to follow-up. Any 
change in severity or suspected relationship to study treatment must be assessed at each visit 
(or more frequently, if necessary). 
Progression of malignancy (including fatal outcomes), if documented by use of appropriate 
method (for example, as per RECIST criteria for solid tumors or as per Cheson's guidelines for 
hematological malignancies), should not be reported as a serious adverse event, except if the 
Investigator considers that progression of malignancy is related to study treatment. 
Adverse events separate from the progression of malignancy (for example deep vein thrombosis 
at the time of progression or hemoptysis concurrent with finding of disease progression) will 
be reported as per usual guidelines used for such events with proper attribution regarding 
causality to the study treatment. 
Timeframe of recording of AEs 
AE recording for each participant should be continued until 8 days after the last dose of study 
treatment (i.e. Day 9) (On and after Day 10, SAEs should be reported only if the investigator 
suspects a causal relationship to study treatment). 
8.6.2 
Serious adverse events 
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] 
undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following 
criteria: 
• fatal 
• life-threatening 
Life-threatening in the context of a SAE refers to a medical occurrence in which the 
participant was at risk of death at the time of the reaction; it does not refer to a medical 
occurrence that hypothetically might have caused death if it were more severe (please 
refer to the ICH-E2D Guidelines). 
• results in persistent or significant disability/incapacity 
• constitutes a congenital anomaly/birth defect, fetal death or a congenital abnormality or 
birth defect 
• requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
• elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 

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• social reasons and respite care in the absence of any deterioration in the participant’s 
general condition 
• treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 
• is medically significant, e.g. defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life-threatening or result in death or hospitalization but might jeopardize the participant or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant.” Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that 
do not result in hospitalization or development of dependency. Any suspected transmission via 
a medicinal product of an infectious agent is also considered a serious adverse reaction. 
All new malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met and the malignant neoplasm is not a disease progression of the 
study indication. 
8.6.3 
SAE reporting 
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
has provided informed consent until 8 days after the last dose of study treatment (i.e. Day 9) 
must be reported to Novartis safety immediately, without undue delay, but under no 
circumstances later than within 24 hours of obtaining knowledge of the events (On and after 
Day 10, SAEs should be reported only if the investigator suspects a causal relationship to study 
treatment). Detailed instructions regarding the submission process and requirements are to be 
found in the Investigator folder provided to each site. Information about all SAEs is collected 
and recorded on the Serious Adverse Event Report Form. All applicable sections of the form 
must be completed in order to provide a clinically thorough report. 
The investigator must review and provide an assessment of causality for each SAE. There may 
be situations in which an SAE has occurred, and the investigator has minimal information to 
include in the initial report to Novartis. However, it is very important that the investigator 
always makes an assessment of causality for every event before the initial transmission of the 
SAE data to Novartis. The investigator may change their opinion of causality in light of follow-
up information and send an SAE follow-up report with the updated causality assessment. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
immediately, without undue delay, but under no circumstances later than within 24 hours of the 
Investigator receiving the follow-up information. 
Any SAEs experienced after the 30-day period after dosing of investigational drug should only 
be reported to Novartis Safety if the Investigator suspects a causal relationship to study 
treatment, unless otherwise specified by local law/regulations. 
Reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs) 

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If an SAE is not previously documented in the IB or product information for marketed products 
and is thought to be related to any study treatment, Novartis may urgently require further 
information from the investigator for HA reporting. Novartis may need to issue an Investigator 
Notification (IN) to inform all investigators involved in any study with the same study treatment. 
SUSARs will be reported to the competent authorities and relevant ethics committees in 
accordance with national regulatory requirements in participating countries, including EU 
Clinical Trial Regulation 536/2014. 
8.6.4 
Pregnancy 
Pregnancies 
Contraception measures are not required. However, if a female trial participant becomes 
pregnant, the pregnancy consent form should be presented to the trial participant. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
or elective termination of a pregnancy for medical reasons will be reported as an AE or 
SAE. 
• Abnormal pregnancy outcomes (e.g. spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported as 
such. 
• Any post study pregnancy-related SAE considered reasonably related to the study 
treatment by the Investigator will be reported to Novartis/Sponsor as described 
in Section 8.6.3. While the Investigator is not obligated to actively seek this information in 
former study participants/pregnant female partner, he or she may learn of an SAE through 
spontaneous reporting. 
Pregnancies  
If a female trial participant becomes pregnant, the pregnancy consent form should be presented 
to the trial participant. The participant must be given adequate time to read, review and sign the 
pregnancy consent form. This consent form is necessary to allow the Investigator to collect and 
report information regarding the pregnancy. To ensure participant safety, each pregnancy 
occurring after signing the informed consent must be reported to Novartis within 24 hours of 
learning of its occurrence. The pregnancy should be followed up to determine outcome, 
including spontaneous or voluntary termination, details of the birth, and the presence or absence 
of any birth defects, congenital abnormalities, or maternal and/or newborn complications. 
Pregnancy should be recorded and reported by the Investigator to the Novartis. Pregnancy 
follow-up should be recorded on the same form and should include an assessment of the 
possible relationship to the study treatment any pregnancy outcome. Any SAE experienced 
during pregnancy must be reported. 
After consent is provided, the pregnancy reporting will occur up to one year after the estimated 
date of delivery. 

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8.6.5 
Reporting of study treatment errors, study treatment misuse/abuse 
and overdose 
Study treatment errors are unintentional errors in the prescribing, dispensing, and administration 
of study treatment. 
Study treatment misuse refers to situations where the study treatment is intentionally and 
inappropriately used not in accordance with the protocol. 
Study treatment abuse corresponds to the persistent or sporadic, intentional excessive use of 
study treatment, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol, including misuse or 
abuse, must be reported on the AE CRF. 
8.6.6 
Adverse events of special interest 
Not applicable. 
8.7 
Pharmacokinetics 
PK samples will be collected at the visits defined in Section 1.3 Schedule of Activities. Follow 
instructions outlined in the Laboratory Manual regarding sample collection, numbering, 
processing and measurement. See the potential use of residual samples for more information. 
The number of samples/blood draws and total blood volume collected will not exceed those 
stated in the protocol. 
PK samples will be obtained and evaluated in 4-6 participants (preferably in patients) enrolled 
in the selected clinical sites on the imaging day. 
Blood samples will be counted at the investigational site in an accurately calibrated gamma 
counter (e.g. NaI spectrometer) with a suitable reference source of 68Ga of known activity 
counted in the same geometry as that of the biological samples (e.g. 1 mL in a vial). Samples 
will be collected at the timepoints described in Table 8-5. Further details about sample 
collection and radioactivity measurement are provided in the Laboratory Manual. 
All data including but not limited to actual date and time of blood sampling, date and time of 
measurement by gamma counter, exact volume of sample measured (including any dilutions if 
applicable) and activity counted by gamma counter must be recorded in the appropriate blood 
collection eCRF page. 
Radioactivity concentrations will be expressed in mass per volume units and, if deemed 
necessary, other units (e.g. radioactivity per volume). In order to determine specific activity for 
the time of injection, the total peptide content, radioactivity after radiolabeling, and date and 
time of measurement must be recorded in the appropriate eCRF. 
8.7.1 
Pharmacokinetic blood collection and handling 
Refer to the [AAA501A11301 Laboratory Manual] for detailed instructions for the collection, 
handling, and shipment of PK samples. 
Blood samples will be taken by either direct venipuncture or an indwelling cannula inserted in 
a forearm vein. At specified time points described in Table 8-5, 1 mL blood will be transferred 

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to the tube or plate for the measurement of radioactivity by gamma counter. The exact date and 
time of dosing, as well as the date and actual time of blood sampling must be recorded on the 
appropriate eCRF page. 
Table 8-5 
Pharmacokinetic blood collection log 
Treatment Period or 
Cycle 
Day 
Scheduled Time 
Point (min) 
Time range 
1 
1 
Pre-dose / 0 
- 
1 
1 
5 
± 3 min 
1 
1 
15 
± 5 min 
1 
1 
30 
± 5 min 
1 
1 
45 
± 5 min 
1 
1 
60 
± 10 min 
1 
1 
120 
± 30 min 
1 
1 
180 
± 30 min 
8.7.2 
Analytical method 
Radioactivity in blood for [68Ga]Ga-DOTA-TATE will be measured at the investigational site, 
with a properly calibrated gamma counter or similar system and must be recorded on the 
appropriate eCRF. Both lower limit of quantification (LLOQ) and upper limit of quantification 
(ULOQ) will be determined for each analytical instrument at the investigational sites and must 
be recorded with the calibration factor on the appropriate eCRF. 
8.8 
Biomarkers 
Not applicable. 
8.9 
Immunogenicity assessments 
Not applicable. 
8.9.1 
Immunogenicity blood sample collection and handling 
Not applicable. 
8.9.2 
Immunogenicity analytical method(s) 
Not applicable. 
8.10 
Health economics OR Medical resource utilization and health 
economics 
Not applicable. 
9 
Statistical considerations 
Efficacy and safety analyses will be conducted for each analysis set respectively at the time all 
participants will have completed the study. 

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Any data analysis carried out independently by the investigator should be submitted to Novartis 
before publication or presentation. 
9.1 
Analysis sets 
The Full Analysis Set (FAS) comprises all enrolled participants. 
The Efficacy Analysis Set (EFF) comprises all enrolled participants who were administered 
with [68Ga]Ga-DOTA-TATE. Patients with confirmed/suspected NENs must have both results 
of [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM. HVs must have result of [68Ga]Ga-
DOTA-TATE PET/CT imaging. If at least 1 central reader cannot judge results for all CIM or 
[68Ga]Ga-DOTA-TATE PET/CT imaging due to imaging quality, the results are considered as 
"Not evaluable". Those participants will be excluded from the EFF. 
The Safety Set comprises all participants who received any dose of [68Ga]Ga-DOTA-TATE. 
The Pharmacokinetic analysis set (PAS) includes all participants who provided at least one 
evaluable PK concentration. A profile considered evaluable if all of the following conditions 
are satisfied: 
• Participant received the study drug 
• Participant provided at least one primary PK parameter 
9.2 
Statistical analyses 
9.2.1 
General considerations 
Grouping strategy 
For some efficacy analyses (subject/region-level sensitivity, specificity, PPV, NPV and 
accuracy), HVs will be categorized in CIM negative population (TN or FP) without CIM. If 
there are participants enrolled as patients with suspected NENs but founded not to have NENs 
based on CIM, they will be also categorized in this population. 
Other than those above: 
Analyses will be conducted by patients with confirmed/suspected NENs and HVs. 
Descriptive statistics 
Categorical data will be presented as frequencies and percentages. For continuous data, mean, 
standard deviation, median, minimum, and maximum will be presented. For selected parameters, 
25th and 75th percentiles will also be presented. 
Baseline 
The last available assessment including unscheduled assessments before injection of study drug 
is taken as “baseline” value or “baseline” assessment. 
If participants have no value as defined above, the baseline result will be missing. 

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9.2.2 
Participant demographics and other baseline characteristics 
Demographic and other baseline data including disease characteristics will be summarized 
descriptively for the FAS and the EFF. 
Relevant medical histories and current medical conditions at baseline will be summarized by 
system organ class (SOC) and preferred term (PT) for the FAS and the EFF. 
9.2.3 
Treatments 
The actual received [68Ga]Ga-DOTA-TATE dose and time interval from injection of [68Ga]Ga-
DOTA-TATE to PET/CT acquisition start will be summarized by descriptive statistics using 
the Safety Set. All dose administration records will be listed. 
Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be summarized according to the Anatomical Therapeutic Chemical (ATC) 
classification system for the FAS. 
9.3 
Primary endpoint(s)/estimand(s) analysis 
The primary objectives of the study are described in Table 3-1. 
Efficacy analyses will be performed for the EFF. 
9.3.1 
Definition of primary endpoint(s) 
The co-primary endpoints of the study are subject-level sensitivity and specificity. 
Subject-level sensitivity 
Subject-level sensitivity is defined as the proportion of [68Ga]Ga-DOTA-TATE PET/CT 
imaging positive participants (i.e. TP participants) among CIM positive participants (i.e. TP or 
FN participants). 
Subject-level specificity 
Subject-level specificity is defined as the proportion of [68Ga]Ga-DOTA-TATE PET/CT 
imaging negative participants (i.e. TN participants) among CIM negative participants (i.e. TN 
or FP participants). 
Table 9-1 
Sensitivity and Specificity 
 
Conventional Imaging (CIM) 
Positive 
Negative 
[68Ga]Ga-DOTA-TATE 
PET/CT imaging 
Positive 
True Positive (TP) 
False Positive (FP) 
Negative 
False Negative (FN) 
True Negative (TN) 
Sensitivity: TP / (TP + FN), Specificity: TN / (TN + FP) 
Where TP, FP, TN, FN participants are defined as follows: 
• TP participants are those who show at least one lesion based on both [68Ga]Ga-DOTA-
TATE PET/CT imaging and CIM by central read. 

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• FP participants are those who show at least one lesion based on [68Ga]Ga-DOTA-TATE 
PET/CT imaging but do not show any lesion based on CIM by central read. 
• TN participants are those who do not show any lesion based on both [68Ga]Ga-DOTA-
TATE PET/CT imaging and CIM by central read. 
• FN participants are those who do not show any lesion based on [68Ga]Ga-DOTA-TATE 
PET/CT imaging but show at least one lesion based on CIM by central read. 
9.3.2 
Statistical model, hypothesis, and method of analysis 
To address the co-primary objectives, following analyses will be conducted. 
Subject-level sensitivity and its 95% exact confidence interval (CI) will be calculated based on 
the binomial distribution. The lower bound of the 95% exact CI for subject-level sensitivity 
should be greater than 0.7 to attain the first co-primary objective. 
Subject-level specificity and its 95% exact CI will be calculated based on the binomial 
distribution. The lower bound of the 95% exact CI for subject-level specificity should be greater 
than 0.6 to attain the second co-primary objective. 
9.3.3 
Handling of intercurrent events of primary estimand (if applicable) 
Not applicable. 
9.3.4 
Handling of missing values not related to intercurrent event 
This is a diagnostic study and primary endpoints are calculated on the basis of [68Ga]Ga-DOTA-
TATE PET/CT imaging and CIM assessments. The primary analysis will be conducted for the 
EFF and missing data related to primary endpoints will not be occurred in the population. 
9.3.5 
Multiplicity adjustment (if applicable) 
Not applicable. 
9.3.6 
Sensitivity analyses 
Not applicable. 
9.3.7 
Supplementary analysis 
If the primary endpoints of subject-level sensitivity and specificity are met, following 
supplementary analyses will be conducted. 
• TP, FP, FN, TN, sensitivity, specificity and corresponded exact 95% CI will be shown for 
each 3 central readers respectively. 
• If there are participants with not evaluable [68Ga]Ga-DOTA-TATE PET/CT imaging, 
those participants' results will be assumed all positive or all negative respectively and each 
analysis will be performed for primary endpoints. 
• The subgroup analyses using descriptive statistics and 95% CI to assess the homogeneity 
of the diagnostic performance of [68Ga]Ga-DOTA-TATE PET/CT imaging across 
demographic and baseline disease characteristics will also be performed. Important 
subgroups will be specified in the SAP. 

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9.4 
Secondary endpoint(s)/estimand(s) analysis 
The secondary objectives of the study are described in Table 3-1. 
Efficacy analyses will be performed for the EFF. 
9.4.1 
Efficacy and/or pharmacodynamic endpoint(s) 
Subject-level assessments 
Subject-level positive predictive values (PPV) is defined as the proportion of TP participants 
among [68Ga]Ga-DOTA-TATE PET/CT imaging positive participants (i.e. TP or FP 
participants). 
Subject-level negative predictive values (NPV) is defined as the proportion of 
TN participants among [68Ga]Ga-DOTA-TATE PET/CT imaging negative participants (i.e. TN 
or FN participants). 
Subject-level accuracy is defined as the proportion of TP and TN participants among all 
patients in the EFF (i.e. TP+TN+FP+FN participants). 
Subject-level PPV, NPV, accuracy will be summarized respectively with corresponded exact 
95% CI. 
Region-level assessments 
Region-level sensitivity is defined as the proportion of [68Ga]Ga-DOTA-TATE PET/CT 
imaging positive regions (TP regions) among CIM positive regions (i.e. TP or FN regions). 
Region-level specificity is defined as the proportion of [68Ga]Ga-DOTA-TATE PET/CT 
imaging negative regions (TN regions) among CIM negative regions (i.e. TN or FP regions). 
Region-level PPV is defined as the proportion of regions which are positive on both [68Ga]Ga-
DOTA-TATE PET/CT imaging and CIM (TP regions) among [68Ga]Ga-DOTA-TATE PET/CT 
imaging positive regions (i.e. TP or FP regions). 
Region-level NPV is defined as the proportion of regions which are negative on both [68Ga]Ga-
DOTA-TATE PET/CT imaging and CIM (TN regions) among [68Ga]Ga-DOTA-TATE 
PET/CT imaging negative regions (i.e. TN or FN regions). 
Region-level accuracy is defined as the proportion of regions which are CIM and [68Ga]Ga-
DOTA-TATE PET/CT imaging positive (TP regions) or negative (TN regions)  among regions 
detected by CIM and [68Ga]Ga-DOTA-TATE PET/CT imaging (i.e. TP+TN+FP+FN regions). 
Where TP, FP, TN, FN regions are defined as follows: 
• TP regions are the regions which show at least one lesion based on both [68Ga]Ga-DOTA-
TATE PET/CT imaging and CIM by central read. 
• FP regions are the regions which show at least one lesion based on [68Ga]Ga-DOTA-
TATE PET/CT imaging but do not show any lesion based on CIM by central read. 
• TN regions are the regions which do not show any lesion based on both [68Ga]Ga-DOTA-
TATE PET/CT imaging and CIM by central read. 

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• FN regions are the regions which do not show any lesion based on [68Ga]Ga-DOTA-
TATE PET/CT imaging but show at least one lesion based on CIM by central read. 
Region-level sensitivity, specificity, PPV, NPV, accuracy will be summarized respectively 
with corresponded exact 95% CI by regions. Region consists of liver, pancreas, gastrointestinal, 
lymph nodes and others. 
Number of lesions detected by imaging 
For region-level, number of lesion detected by [68Ga]Ga-DOTA-TATE PET/CT imaging and 
CIM will be counted. Regarding [68Ga]Ga-DOTA-TATE PET/CT imaging, individual and 
mean number of lesions detected by each 3 central readers will be presented. Regarding CIM, 
each number of lesions detected by [111In]In-Pentetreotide SPECT/CT and High Resolution CT 
with contrast (or MRI if CT with contrast is medically contraindicated) will be presented. 
Impact on treatment decision 
Numbers and percentages of participants for each intended treatment plan collected from 
physician at pre and post [68Ga]Ga-DOTA-TATE PET/CT imaging will be summarized. 
Summary statistics of participants for the change of intended treatment plan will also be 
presented. 
Inter-reader variability 
Inter-reader variability for [68Ga]Ga-DOTA-TATE PET/CT imaging is defined as agreement 
rate among reader determinations and will be assessed by Fleiss' Kappa statistics. Inter-reader 
variability (%) and its normality 95% CI will be presented. 
Lesion-level concordance rate for SSTR 
The lesion-level concordance rate for SSTR between [68Ga]Ga-DOTA-TATE PET/CT imaging 
local read and local histopathology result among legions which is available, will be calculated. 
The rate is defined as the proportion of lesions which are positive or negative on both local read 
of [68Ga]Ga-DOTA-TATE PET/CT imaging and local histopathology among lesions detected 
by local histopathology. 
9.4.2 
Safety endpoints 
For all safety analyses, the safety set will be used. All listings and tables will be presented by 
group (i.e. Patients with confirmed/suspected NENs and HVs). 
Safety summaries (tables, figures) include only data from the on-treatment period with the 
exception of baseline data which will also be summarized where appropriate (e.g. change from 
baseline summaries). In addition, a separate summary for death including on treatment and post 
treatment deaths will be provided. In particular, summary tables for adverse events (AEs) will 
summarize only on-treatment events, with a start date during the on-treatment period 
(treatment-emergent AEs). 
The overall observation period will be divided into three mutually exclusive segments: 

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1. Pre-treatment period: from day of participant’s informed consent to the day before dosing 
of investigational drug. 
2. On-treatment period: from day of dosing of investigational drug  to 8 days after dosing of 
investigational drug. 
3. Post-treatment period: starting 9 days after dosing of investigational drug. 
Adverse events 
The incidence of treatment-emergent adverse events (new or worsening from baseline) will be 
summarized by system organ class and or preferred term, severity (based on CTCAE grades), 
type of adverse event, relation to study treatment. 
Serious adverse events, non-serious adverse events and adverse events of special interest (AESI) 
during the on-treatment period will be tabulated. 
All deaths (on-treatment and post-treatment) will be summarized. 
All AEs, deaths, and serious adverse events (including those from the pre and post-treatment 
periods) will be listed and those collected during the pre-treatment and post-treatment period 
will be flagged. 
Vital signs 
Notable vital sign values will be summarized by visit/time. 
12-lead ECG 
ECG abnormalities will be summarized. 
Clinical laboratory evaluations 
Grading of laboratory values will be assigned programmatically as per NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0. The calculation of CTCAE 
grades will be based on the observed laboratory values only, clinical assessments will not be 
taken into account. 
CTCAE Grade 0 will be assigned for all non-missing values not graded as 1 or higher. Grade 5 
will not be used. 
For laboratory tests where grades are not defined by CTCAE version 5.0, results will be 
categorized as low/normal/high based on laboratory normal ranges. 
The following summaries will be generated separately for hematology, and biochemistry tests: 
For laboratory tests where grades are defined by CTCAE version 5.0: 
• Worst post-baseline CTCAE grade (regardless of the baseline status). Each participant 
will be counted only once for the worst grade observed post-baseline. 
• Shift tables using CTCAE version 5.0 grades to compare baseline to the worst on-
treatment value. 
For laboratory tests where grades are not defined by CTCAE version 5.0: 

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• Shift tables using the low/normal/high/ (low and high) classification to compare baseline 
to the worst on-treatment value. 
Listing of laboratory data will be produced with values flagged to show the corresponding 
CTCAE version 5.0 grades if applicable and the classifications relative to the laboratory normal 
ranges. 
9.4.3 
Pharmacokinetics 
Descriptive summary statistics of [68Ga]Ga-DOTA-TATE blood concentration data will be 
provided by participant, and visit/sampling time point, including the frequency of 
concentrations below the LLOQ and reported as zero. 
Summary statistics will include mean (arithmetic and geometric), SD, CV (arithmetic and 
geometric), median, minimum, and maximum. 
Drug concentrations below LLOQ will be treated as missing for the calculation of the geometric 
means and geometric CV%, and as zero for all other calculations including calculation of PK 
parameters. 
Descriptive summary statistics will include mean (arithmetic and geometric), SD, and CV 
(arithmetic and geometric), median, minimum, and maximum. 
The PAS will be used in all pharmacokinetic data analysis and PK summary statistics. 
Pharmacokinetic variables: 
The following pharmacokinetic parameters will be determined using the actual recorded 
sampling time s and non-compartmental method(s) with Phoenix WinNonlin (Version 6.4 or 
higher): 
AUCinf, AUClast, Cmax, Tmax, T1/2, Lambda_z, CL and Vz. 
In addition, the following pharmacokinetic parameters may be determined, if deemed 
appropriate, using the actual recorded sampling time s and two-compartmental method(s) with 
Phoenix WinNonlin (Version 6.4 or higher): 
V1, K10, K12, K21, AUC, K10 T1/2, Alpha, Beta, Alpha T1/2, Beta T1/2, V2, CL. 
Bio-fluid concentrations will be expressed in mass per volume units and, if deemed necessary, 
other units (e.g. radioactivity per volume). All concentrations below the limit of quantitation or 
missing data will be reported as such in the concentration data listings. Concentrations below 
the limit of quantitation will be treated as zero in summary statistics. 
Pharmacokinetic parameters will be provided by participants. Descriptive statistics of all 
pharmacokinetic parameters will include arithmetic and geometric mean, median, SD, and CV, 
geometric CV, minimum, and maximum. Zero concentrations will not be included in the 
geometric mean calculation. Since Tmax is generally evaluated by a nonparametric method, 
median values and ranges will be given for this parameter. 

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Table 9-2 
Non-compartmental pharmacokinetic parameters 
AUClast 
The AUC from time zero to the last measurable 
concentration sampling time (tlast) (mass x time 
x volume-1) 
AUCinf 
The AUC from time zero to infinity (mass x time 
x volume-1) 
Cmax 
The maximum (peak) observed plasma, blood, 
serum, or other body fluid drug concentration 
after single dose administration (mass x volume-
1) 
Tmax 
The time to reach maximum (peak) plasma, 
blood, serum, or other body fluid drug 
concentration after single dose administration 
(time) 
Lambda_z 
Smallest (slowest) disposition (hybrid) rate 
constant (time-1) may also be used for terminal 
elimination rate constant (time-1) 
T1/2 
The elimination half-life associated with the 
terminal slope (λz) of a semi logarithmic 
concentration-time curve (time). Use qualifier for 
other half-lives 
CL 
The total body clearance of drug from the 
plasma (volume x time-1) 
Vz 
The apparent volume of distribution during 
terminal phase (associated with λz) (volume) 
 
 
 
 
 
 
 

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9.6 
(Other) Safety analyses 
Not applicable. 
9.7 
Other analyses 
Not applicable. 
9.8 
Interim analysis 
Not applicable. 
9.9 
Sample size determination 
9.9.1 
Primary endpoint(s) 
The primary endpoints of the study are subject-level sensitivity and specificity based on central 
read. 
The sample size was calculated based on the following assumptions for primary endpoints. 
• Assumptions for subject-level sensitivity: expected sensitivity of 90% and threshold of 
70% 
• Assumptions for subject-level specificity: expected specificity of 90% and threshold of 
60% 
The expected sensitivity and specificity are respectively set as 90% based on the systematic 
review publication on [68Ga]Ga-DOTA-TATE (Deppen et al 2016a). The thresholds of 70% for 
sensitivity and 60% for specificity are set by referring to phase III study of [64Cu]Cu-DOTA-
TATE (Delpassand et al 2020) and the thresholds will be considered reasonable to show clinical 
relevant diagnostic performance in this study. For sensitivity, 47 participants with positive 
result in CIM are required to reject the null hypothesis of sensitivity ≤ 70% with 1-sided alpha 
level of 2.5% and ≥ 90% power with exact binomial test. For specificity, 23 participants with 
negative result in CIM are required to reject the null hypothesis of specificity ≤ 60% with 1-
sided alpha level of 2.5% and ≥ 90% power with exact binomial test. Therefore, 47 

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confirmed/suspected NEN patients (expected to be positive in CIM) and 23 HVs (negative in 
CIM) are required. As a result, 70 participants are required as Efficacy Analysis Set (EFF) in 
total. The study enrollment will continue until 70 participants in the EFF. 
Table 9-3 
Sensitivity of power to changes in number of participants 
N_Sensitivity 
Power for Sensitivity 
N_Specificity 
Power for Specificity 
42 
87.9% 
28 
94.5% 
43 
86.7% 
27 
95.3% 
44 
85.4% 
26 
96.0% 
45 
92.4% 
25 
90.2% 
46 
91.6% 
24 
91.5% 
47 
90.7% 
23 
92.7% 
The N for sensitivity is based on NEN patients with positive result in CIM. The N for specificity is based 
on NEN patients with negative result in CIM in addition to HVs (i.e., some NEN patients out of 47 
patients will be used for specificity estimation instead of sensitivity if the result in CIM is negative). 

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10 
Supporting documentation and operational considerations 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1 
Regulatory and ethical considerations 
This study was designed and will be implemented, executed and reported in accordance with 
the protocol and the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) international ethical guidelines 
• Applicable ICH Tripartite Guidelines for Good Clinical Practice (GCP) 
• Applicable local regulations (including European Directive 2001/20/EC or European 
Clinical Trial Regulation 536/2014, US CFR 21) 
The protocol, protocol amendments, ICF, Investigator’s Brochure, [IDFU], and other relevant 
documents (e.g. advertisements) must be submitted to an IRB/IEC by the Investigator and 
reviewed and approved by the IRB/IEC before the study is initiated at that specific site. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
The Investigator will be responsible for the following: 
• Signing a protocol signature page confirming his/her agreement to conduct the study in 
accordance with these documents and all of the instructions and procedures found in this 
protocol and to give access to all relevant data and records to Novartis, Eckert & Ziegler 
Radiopharma GmbH monitors, auditors, Novartis, Eckert & Ziegler Radiopharma 
GmbH Quality Assurance representatives, designated agents of Novartis, Eckert & Ziegler 
Radiopharma GmbH, IRBs/IECs, and regulatory authorities as required 
• Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• Taking any immediate action required for the safety of any participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, 
Novartis/Sponsor must be notified of this action and the IRB/IEC at the study site must be 
informed according to local regulations. 
• Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical 
studies (if applicable), European Medical Device Regulation 2017/745 for clinical device 
research (if applicable), and all other applicable local regulations 
• Informing Novartis, Eckert & Ziegler Radiopharma GmbH immediately if an inspection 
of the clinical site is requested by a regulatory authority 

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10.1.2 
Informed consent process 
The Investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the participant and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representatives will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and data protection 
requirements, where applicable, and the IRB/IEC or study center. 
Informed consent must be obtained before conducting any study-specific procedures (e.g. all of 
the procedures described in the protocol). The process of obtaining informed consent must be 
documented in the participant source documents. 
The medical record must include a statement that written informed consent was obtained before 
the participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
A copy of the ICF(s) must be provided to the participant. 
Participants who are rescreened are required to sign a new ICF. 
If applicable, in cases where the participant's representative(s) gives consent (if allowed 
according to local requirements), the participant must be informed about the study to the extent 
possible given his/her level of understanding. If the participant is capable of doing so, the 
participant must indicate agreement by personally signing and dating the written informed 
consent document. 
Eligible participants may only be included in the study after providing (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent. 
If applicable, in cases where the participant's representative(s) gives consent (if allowed 
according to local requirements), the participant must be informed about the study to the extent 
possible given his/her level of understanding. If the participant is capable of doing so, he/she 
must indicate agreement by personally signing and dating the written informed consent 
document. 
Common side effects already known about the study treatment will be included in the ICF and 
must be discussed with the participant upon obtaining consent and during the study as needed. 
Any new information related to the safety profile that is identified between IB updates will be 
communicated as appropriate, for example, via an Investigator notification or an aggregate 
safety finding. New information might require an update to the ICF and discussion with the 
participant. 
The following informed consents are included in this study: 
• Main study consent, included: 
• A subsection with a separate signature for the ‘Optional Consent for Additional 
Research’ to allow future research on data/samples collected during this study 
• Optional consent for activities that may be done outside of the study site 
• As applicable, Pregnancy Outcomes Reporting Consent for female participants or the 
female partners of any male participants 

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As applicable, information sheet for female partners of male participants 
A copy of the approved version of all consent forms must be provided to Novartis, Eckert & 
Ziegler Radiopharma GmbH after IRB/IEC approval. 
10.1.3 
Data protection 
Participants will be assigned a unique identifier. Any participant records or datasets that are 
transferred to Novartis, Eckert & Ziegler Radiopharma GmbH will contain the identifier only; 
participant names or any information which would make the participant identifiable will not be 
transferred. 
The participant must be informed that his/her personal study-related data will be used 
by Novartis, Eckert & Ziegler Radiopharma GmbH in accordance with local data protection 
law. The level of disclosure must also be explained to the participant who will be required to 
give consent for their data to be used as described in the informed consent. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by Novartis, Eckert & 
Ziegler Radiopharma GmbH, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities. 
Novartis and Eckert & Ziegler Radiopharma GmbH have appropriate processes and policies in 
place to handle personal data breaches according to applicable privacy laws. 
10.1.4 
Committees structure 
10.1.4.1 Data Monitoring Committee 
Not applicable. 
10.1.4.2 Steering Committee 
Not applicable. 
10.1.4.3 Adjudication committee 
Not applicable. 
10.1.5 
Data quality assurance 
Monitoring strategy, methods, responsibilities, and requirements are provided in the monitoring 
plan, contracts. Details may include definition of study critical data items and processes (e.g. 
risk-based initiatives in operations and quality such as risk management and mitigation 
strategies and analytical risk-based monitoring), including handling of noncompliance issues 
and monitoring techniques (central, remote, or on-site monitoring). 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of Novartis and Eckert & Ziegler Radiopharma 

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GmbH. No records may be transferred to another location or party without written notification 
to Novartis and Eckert & Ziegler Radiopharma GmbH. 
10.1.5.1 Data collection 
Data not requiring a separate written record will be defined in the protocol and 
Section 1.3 Schedule of Activities and can be recorded directly on the CRFs. All other data 
captured for this study will have an external originating source (either written or electronic) 
with the CRF not being considered as source. 
Designated Investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (CRF). The CRFs have been built using fully validated secure web-enabled 
software that conforms to 21 CFR Part 11 requirements, Investigator site staff will not be given 
access to the EDC system until they have been certified as trained. Automatic validation 
programs check for data discrepancies in the CRFs, allow modification and/or verification of 
the entered data by the Investigator staff. 
The Investigator/designee is responsible for assuring that the data entered into CRF is complete, 
accurate, and that entry and updates are performed in a timely manner e.g. within 5 days of visit. 
The Investigator must certify that the data entered are complete and accurate. 
After final database lock, the Investigator will receive copies of the participant data for 
archiving at the investigational site. 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
10.1.5.2 Database management and quality control 
Novartis personnel (or designated CRO) will review the data entered by investigational staff 
for completeness, accuracy and scientific/medical plausibility. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the investigational site via the EDC system. Designated Investigator 
site staff are required to respond promptly to queries and to make any necessary changes to the 
data. 
Concomitant treatments and prior medications entered into the database will be medically coded 
using the World Health Organization (WHO) Drug Reference List, which employs the 
Anatomical Therapeutic Chemical classification system. Medical history/current medical 
conditions and adverse events will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) terminology. 
At the conclusion of a non-IRT study, the occurrence of any emergency code breaks will be 
determined after return of all code break reports and unused supplies to Novartis. 
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked and the treatment codes will be unblinded and made 
available for data analysis/moved to restricted area to be accessed by independent programmer 
and statistician. 
 

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10.1.6 
Source documents 
Data reported on the CRF or entered in the CRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
Investigator may need to request previous medical records or transfer records. 
The Investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. The Investigator must also keep the original 
informed consent form signed by the participant (a signed copy is given to the participant). 
Study monitors will perform source data verification to confirm that data entered into the CRF 
by authorized site personnel are accurate, complete, and verifiable from source documents; that 
the safety and rights of participants are being protected; and that the study is being conducted 
in accordance with the currently approved protocol and any other study agreements, ICH GCP, 
and all applicable regulatory requirements. 
Key study personnel must be available to assist the field monitor during these visits. 
10.1.7 
Publication policy 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov and 
as required in EudraCT or CTIS public website. In addition, after study completion and 
finalization of the study report the results of this trial will be submitted for publication and 
posted in a publicly accessible database of clinical trial results, such as the Novartis, Eckert & 
Ziegler Radiopharma GmbH clinical trial results website and all required health authority 
websites (e.g. Clinicaltrials.gov, EudraCT or CTIS public website etc.). 
Summary results of primary and secondary endpoints will be disclosed based upon the global 
Last Participant Last Visit (LPLV) date, since multinational studies are locked and reported 
based upon the global LPLV. 
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided. 
Any data analysis carried out independently by the Investigator must be submitted to 
Novartis/Sponsor before publication or presentation. 
10.1.8 
Protocol adherence and protocol amendments 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of participants should be 
administered as deemed necessary on a case-by-case basis. Under no circumstances including 
incidental collection is an Investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this prohibition, data, information, observation 
would be incidentally collected, the Investigator shall immediately disclose it to Novartis and 
Eckert & Ziegler Radiopharma GmbH and not use it for any purpose other than the study, 
except for the appropriate monitoring on study participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
Investigator feels a protocol deviation would improve the conduct of the study this must be 

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considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and Eckert & Ziegler Radiopharma GmbH and approved by the IRB/IEC and health authorities, 
where required, it cannot be implemented. 
10.1.8.1 Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, Eckert & Ziegler Radiopharma GmbH, health authorities where 
required, and the IRB/IEC prior to implementation. 
Only amendments that are required for participant safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the Investigator is 
expected to take any immediate action required for the safety of any participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis and 
Eckert & Ziegler Radiopharma GmbH should be notified of this action and the IRB/IEC at the 
study site should be informed according to local regulations. 

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10.2 
Appendix 2: Abbreviations and definitions 
10.2.1 
List of abbreviations 
AE 
Adverse Event 
AESI 
Adverse Events of Special Interest 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
APTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AxMP 
Auxiliary Medicinal Product 
BUN 
Blood Urea Nitrogen 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CIM 
Conventional Imaging 
CIOMS  
Council for International Organizations of Medical Sciences 
CK 
Creatine Kinase 
COA 
Clinical Outcome Assessment 
CONSORT  Consolidated Standards of Reporting Trials 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
CT 
Computerized Tomography 
CTC 
Common Terminology Criteria 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTT 
Clinical Trial Team 
CV 
coefficient of variation 
DILI  
Drug-Induced Liver Injury 
DLT 
Dose Limiting Toxicity 
EANM 
European Association of Nuclear Medicine 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic Case Report/Record Form 
ED 
Effective Dose 
EDC 
Electronic Data Capture 
EFF 
Efficacy Analysis Set 
EMA 
European Medicines Agency  
EOS 
End Of Study 
EU  
European Union 
FAS  
Full Analysis Set 
FDG  
Fluorodeoxyglucose 
FN  
False Negative 
FP  
False Positive 

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GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
i.v. 
intravenous 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IMP 
Investigational Medicinal Product 
IN 
Investigator Notification 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
kg  
kilogram 
L  
Liter 
LDH 
lactate dehydrogenase 
LFT 
Liver function test 
LLOQ 
lower limit of quantification 
LPLV  
Last Patient Last Visit 
MBq  
Mega-Becquerel 
MCH  
Mean Corpuscular Hemoglobin 
mCi  
Millicurie 
MedDRA 
Medical dictionary for regulatory activities 
mg 
milligram(s) 
min  
minute(s) 
mL 
milliliter(s) 
MRI  
Magnetic Resonance Imaging 
mSV  
millisievert 
PA 
Posteroanterior 
PAS 
Pharmacokinetic Analysis Set 
PET  
Positron Emission Tomography 
PK 
Pharmacokinetic(s) 
PPV  
Positive Predictive Value 
PRO 
Patient Reported Outcomes 
PS&PV 
Patient Safety and Pharmacovigilance 
PSMA 
Prostate-specific membrane antigen 
PT 
prothrombin time 
RECIST 
Response Evaluation Criteria In Solid Tumors 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SoA 
Schedule of Activities 

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SoT  
Standard of Truth 
SPECT  
Single-photon Emission Computerized Tomography 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TEAE  
Treatment Emergent Adverse Event 
TN  
True Negative 
TNM  
TNM Classification of Malignant Tumors 
TP  
True Positive 
ULN 
upper limit of normal 
US  
United States  
WHO 
World Health Organization 
10.2.2 
Definitions 
Additional treatment 
Medicinal products that may be used during the clinical trial as described in 
the protocol, but not as an investigational medicinal product (e.g. any 
background therapy) 
Assessment 
A procedure used to generate data required by the study 
Auxiliary Medicinal 
Product 
Medicinal product used for the needs of a clinical trial as described in the 
protocol, but not as an investigational medicinal product (e.g. rescue 
medication, challenge agents, background treatment or medicinal products 
used to assess endpoints in the clinical trial). 
Concomitant therapy is not considered as AxMP. 
Biologic Samples 
A biological specimen including, for example, blood (plasma, serum), 
saliva, tissue, urine, stool, etc. taken from a study participant 
CE marking 
A marking by which a manufacturer indicates that a device is in conformity 
with the applicable requirements set out in European Union legislation 
providing for its affixing. 
CE marking of medical devices is required prior to lawfully placing them on 
the European Union market. 
Clinical Outcome 
Assessment (COA) 
A measure that describes or reflects how a participant feels, functions, or 
survives 
Clinical Trial Team 
A group of people responsible for the planning, execution and reporting of 
all clinical trial activities. Examples of team members include the Study 
Lead, Medical Monitor, Trial Statistician etc. 
Coded Data 
Personal Data which has been de-identified by the investigative center 
team by replacing personal identifiers with a code. 
Cohort 
A group of individuals who share a common exposure, experience or 
characteristic, or a group of individuals followed-up or traced over time 
Control drug 
A study treatment (active or placebo) used as a comparator to reduce 
assessment bias, preserve blinding of investigational drug, assess internal 
study validity, and/or evaluate comparative effects of the investigational 
drug 
Cycles 
Number and timing or recommended repetitions of therapy are usually 
expressed as number of days (e.g. q28 days) 
Discontinuation from 
study 
Point/time when the participant permanently stops receiving the study 
treatment and further protocol required assessments or follow-up, for any 
reason. No specific request is made to stop the use of their samples or 
data. 

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Discontinuation from 
study treatment 
Point/time when the participant permanently stops receiving the study 
treatment for any reason (prior to the planned completion of study 
intervention administration, if any). Participant agrees to the other protocol 
required assessments including follow-up. No specific request is made to 
stop the use of their samples or data. 
Dosage 
Dose of the study treatment given to the participant in a time unit (e.g. 100 
mg once a day, 75 mg twice a day) 
Electronic Data 
Capture (EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical study 
data using data collection systems, such as Web-based applications, 
interactive voice response systems and clinical laboratory interfaces. EDC 
includes the use of Electronic Case Report Forms (CRFs) which are used 
to capture data transcribed from source data/documents used at the point 
of care 
End of the clinical trial 
The end of the clinical trial is defined as the last visit of the last participant. 
Enrollment 
Enrollment will take place at the time when all eligibility requirements are 
confirmed. 
eSource Direct Data 
Capture (DDC) 
eSource Direct Data Capture (DDC) refers to the capture of clinical study 
data electronically, at the point of care. eSource Platform/Applications 
combine source documents and case report forms (CRFs) into one 
application, allowing for the real time collection of clinical trial information to 
Sponsors and other oversight authorities, as appropriate 
Estimand 
As defined in the ICH E9(R1) addendum, estimand is a precise description 
of the treatment effect reflecting the clinical question posed by the trial 
objective. It summarizes at a population-level what the outcomes would be 
in the same participants under different treatment conditions being 
compared. Attributes of an estimand include the population, variable (or 
endpoint) and treatment of interest, as well as the specification of how the 
remaining intercurrent events are addressed and a population-level 
summary for the variable. 
Healthy volunteer 
A person with no known significant health problems who volunteers to be a 
study participant  
Intercurrent events 
Events occurring after treatment initiation that affect either the 
interpretation or the existence of the measurements associated with the 
clinical question of interest. 
Investigational 
Medical Device 
Medical Device being assessed for safety or performance in a clinical 
investigation. This includes devices already on the market and being 
evaluated for new intended uses, new populations, new materials, or 
design changes 
Investigational 
Product/ 
Investigational 
Medicinal product 
A pharmaceutical form of an active ingredient or placebo being tested or 
used as a reference ( such as an active comparator) in a clinical trial, 
including a product with a marketing authorization when used or 
assembled (formulated or packaged) in a way different from the approved 
form, or when used for an unapproved indication, or when used to gain 
further information about an approved use. 
Medication number 
A unique identifier on the label of medication kits 
Mis-randomized 
participants 
Mis-randomized participants are those who were not qualified for 
randomization and who did not take study treatment, but have been 
inadvertently randomized into the study or the participant allocated to an 
invalid stratification factor 

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Off-site 
Describes trial activities that are performed at remote location by an off-site 
healthcare professional, such as procedures performed at a the 
participant's home. 
Off-site healthcare 
Professional (OHP) 
A qualified healthcare professional, who performs certain protocol 
procedures for the participant in an off-site location such as a participant's 
home. 
Other treatment 
Treatment that may be needed/allowed during the conduct of the study 
(e.g. concomitant or rescue therapy) 
Part 
A sub-division of a study used to evaluate specific objectives or contain 
different populations. For example, one study could contain a single dose 
part and a multiple dose part, or a part in participants with established 
disease and in those with newly-diagnosed disease 
Participant 
A trial participant (can be a healthy volunteer or a patient). "Participant" 
terminology is used in the protocol whereas term "Subject" is used in data 
collection 
Participant number 
A unique number assigned to each participant upon signing the informed 
consent. This number is the definitive, unique identifier for the participant 
and should be used to identify the participant throughout the study for all 
data collected, sample labels, etc. 
Patient-Reported 
Outcome (PRO) 
A measurement based on a report that comes directly from the participant 
about the status of a participant's health condition without amendment or 
interpretation of the participant's report by a clinician or anyone else 
Period 
The subdivisions of the trial design (e.g. Screening, Treatment, Follow-up) 
which are described in the Protocol. Periods define the study phases and 
will be used in clinical trial database setup and eventually in analysis 
Perpetrator drug 
A drug which affects the pharmacokinetics of the other drug 
Personal data 
Participant information collected by the Investigator that is coded and 
transferred to Novartis for the purpose of the clinical trial. This data 
includes participant identifier information, study information and biological 
samples. 
Randomization 
The process of assigning trial participants to investigational drug or 
control/comparator drug using an element of chance to determine the 
assignments in order to reduce bias. 
Randomization 
number 
A unique identifier assigned to each randomized participant 
Remote 
Describes any trial activities performed at a location that is not the 
investigative site. 
Rescreening 
If a participant fails the initial screening and is considered as a Screen 
Failure, the participant can be invited once for a new Screening visit after 
medical judgment and as specified by the protocol 
Run-in Failure 
A participant who is screened but not randomized/treated after the run-in 
period (where run-in period requires adjustment to participant's intervention 
or other treatment) 
Screen Failure 
A participant who did not meet one or more criteria that were required for 
participation in the study 
Source 
Data/Document 
Source data refers to the initial record, document, or primary location from 
where data comes. The data source can be a database, a dataset, a 
spreadsheet or even hard-coded data, such as paper or eSource 

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Stage in cancer 
The extent of a cancer in the body. Staging is usually based on the size of 
the tumor, whether lymph nodes contain cancer, and whether the cancer 
has spread from the original site to other parts of the body 
Start of the clinical 
trial 
The start of the clinical trial is defined as the signature of the informed 
consent by the first participant 
Study device 
Study device is a medical device (marketed or investigational) that is used 
in a circumstance that makes it part of the investigation. 
Study treatment 
Any drug or combination of drugs or intervention administered to the study 
participants as part of the required study procedures; includes for example 
investigational drug(s, and controls) 
Tele-visit 
Procedures or communications conducted using technology such as 
telephone or video-conference, whereby the participant is not at the 
investigative site where the Investigator will conduct the trial. 
Treatment arm/group 
A treatment arm/group defines the dose and regimen or the combination, 
and may consist of 1 or more cohorts. 
Treatment of interest 
The treatment of interest and, as appropriate, the alternative treatment to 
which comparison will be made. These might be individual interventions, 
combinations of interventions administered concurrently, e.g. as add-on to 
standard of care, or might consist of an overall regimen involving a 
complex sequence of interventions. This is the treatment of interest used in 
describing the related clinical question of interest, which might or might not 
be the same as the study treatment. 
Variable (or endpoint) 
The variable (or endpoint) to be obtained for each participant that is 
required to address the clinical question. The specification of the variable 
might include whether the participant experiences an intercurrent event. 
Withdrawal of consent 
Withdrawal of consent from the study occurs when the participant explicitly 
requests to stop use of their data and/or biological samples AND no longer 
wishes to receive study treatment, AND does not agree to further protocol 
required assessments. This request should be in writing (depending on 
local regulations) and recorded in the source documentation. 
This request should be distinguished from a request to discontinue the 
study. Other study participant's privacy rights are described in the 
corresponding informed consent form. 

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10.3 
Appendix 3: Clinical laboratory tests 
10.3.1 
Clinically notable laboratory values and vital signs 
The complete NCI CTCAE (version 5.0) can be found at the following site: 
[https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quic
k_Reference_8.] 

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10.4 
Appendix 4: Participant Engagement 
Not Applicable 

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10.5 
Appendix 5: Liver safety monitoring 
Not Applicable 
10.5.1 
Liver event and laboratory trigger definitions & follow-up requirements 
Not Applicable 

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10.6 
Appendix 6: Renal safety monitoring 
Not Applicable 
10.6.1 
Specific Renal Alert Criteria and Actions and Event Follow-up 
Not Applicable 

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11 
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