Clinical trial NCT03697551
Conditions: Breast Cancer
Sponsor: Ipsen
Start date: 2018-10-22; Completion date: 2019-02-06
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this clinical research is to define the optimal uptake time of 68Ga-OPS202 as a PET imaging agent to be used to detect and localize breast cancer somatostatin receptor subtype 2 (SSTR2) positive lesions.

68Ga-OPS202 is a radiolabelled imaging agent to be used in association with PET. 68Ga-OPS202 is made of two main components: 1) OPS202, an antagonistic somatostatin analogue which binds to the somatostatin receptor (type 2) present on the surface of the tumor cells and 2) Gallium 68, a radioisotope that, combined with OPS202, can be seen in the PET scanner.

Detailed description:

Arms: arm 1: A single dose of Satoreotide trizoxetan will be administered as a slow intravenous (i.v.) bolus injected over 1 minute at Baseline/Day 1.
Interventions: intervention 1: Satoreotide trizoxetan
Intervention descriptions: intervention 1: Subjects will receive a single dose of Satoreotide trizoxetan consisting of a peptide mass up to 45 μg, with a radioactivity range of 150-200 MBq. Satoreotide trizoxetan is intended for diagnostic use as a Positron emission tomography/computed tomography (PET/CT) tracer for the imaging of tumours expressing SSTR2.

Protocol documents:
Prot_001.pdf: 
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PROTOCOL TITLE: A NON-RANDOMISED PHASE II STUDY TO EVALUATE THE 
OPTIMAL UPTAKE TIME OF 68GA-OPS202 AS A SSTR2 POSITIVE PET IMAGING 
AGENT IN SUBJECTS WITH NEWLY DIAGNOSED BREAST CANCER 
(Sub-study of Master Protocol Ipsen 001 Version 1.0: 02 February 2018)  
 
STUDY PROTOCOL 
STUDY number: D-FR-01070-003 
68Ga-OPS202  
EudraCT number: 2018-000028-33/NCT Number: XXXX  
Version 4.0, Amendment 3.0: 20 May 2019 
 
Study Sponsor: 
Ipsen Pharma 
65 quai Georges Gorse 
92100 Boulogne-Billancourt 
France 
Tel:  
+33 (0) 1 58 33 50 00 
Fax:  
 
 
Sponsor’s Medically Responsible Person:  
 
 
Ipsen Pharma 
Global Drug Development 
65 quai Georges Gorse  
92100 Boulogne-Billancourt 
France  
Mobile: 
 
 
Pharmacovigilance/Emergency Contact: 
 
 Ipsen Innovation ZI de Courtaboeuf - 5 avenue du 
Canada - 91940 Les Ulis - France 
Phone:   
 
Mobile:  
 
The person listed above is medically qualified and designated by the sponsor as the first point of contact 
for emergency situations. 
For serious adverse events (SAEs) reporting:  
Email address (preferably): 
  
Fax: 
 
              
Persons supplied with this information must understand that it is strictly confidential. 
Information contained herein cannot be disclosed, submitted for publication or used for any 
purpose other than that contemplated herein without the sponsor’s prior written 
authorisation. 
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INVESTIGATOR’S AGREEMENT 
 
Investigator Agreement and Signature: 
I have read and agree to Protocol D-FR-01070-003 entitled: A non-randomised phase II study 
to evaluate the optimal uptake time of 68Ga-OPS202 as a sstr2 positive PET imaging agent in 
subjects with newly diagnosed breast cancer. I am aware of my responsibilities as an 
investigator under the guidelines of Good Clinical Practice (GCP), local regulations (as 
applicable) and the study protocol. I agree to conduct the study according to these guidelines 
and to appropriately direct and assist the staff under my control, who will be involved in the 
study. 
   
NAME: [ ] 
TITLE: 
[PRINCIPAL] 
SIGNATURE: 
 
INVESTIGATOR 
   
   
DATE: 
OFFICE: 
[ ] 
 
[ ] 
 
[ ] 
 
[ ] 
 
[ ] 
   
Sponsor's Representative Signature: 
NAME: 
 
TITLE: 
  
 
 
 Ipsen Biopharm Ltd 
SIGNATURE: 
   
   
DATE: 
OFFICE: 
Ipsen Biopharm Ltd  
 
102 Park Drive 
 
 
Milton Park 
 
 
Abingdon, OX14 4RY 
 
United Kingdom 
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COORDINATING INVESTIGATOR’S AGREEMENT 
 
Coordinating Investigator Agreement and Signature: 
I have read and agree to Protocol D-FR-01070-003 entitled A non-randomised, phase II study 
to evaluate the optimal uptake time of 68Ga-OPS202 as a sstr2 positive PET imaging agent in 
subjects with newly diagnosed breast cancer. I am aware of my responsibilities as a 
coordinating investigator under the guidelines of Good Clinical Practice (GCP), local 
regulations (as applicable) and the study protocol. I agree to conduct the study according to 
these guidelines and to appropriately direct and assist the staff under my control, who will be 
involved in the study. 
   
NAME: 
 
TITLE: 
COORDINATING 
SIGNATURE:_____________________ 
 
INVESTIGATOR 
   
   
DATE:________________________ 
OFFICE: 
 
 
Anichstrasse 35 
 
A - 6020 Innsbruck 
 
Austria 
 
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SUMMARY OF CHANGES 
The current version of the protocol was released on 20 May 2019 and includes Amendment 3. 
For all protocol amendments, amendment forms were prepared and are provided in the 
Appendices listed in Table 1. All modifications (except minor changes) are presented in the 
appendices. 
Table 1 
List of Protocol Amendments 
Amendment 
Release date 
Amendment form 
1 
27 June 2018 
Appendix 1 
2 
14 September 2018 
Appendix 2 
3 
20 May 2019 
Appendix 3 
 
 


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SYNOPSIS 
Name of sponsor/company: IPSEN.  
Name of finished product: 68Ga-OPS202 - 68Ga-satoreotide trizoxetan 
Name of active ingredient(s): 68Ga-OPS202 - INN for OPS202 is satoreotide trizoxetan 
Title of study: A non-randomised, phase II study to evaluate the optimal uptake time of 
68Ga-OPS202 as a sstr2 positive PET imaging agent in subjects with newly diagnosed breast 
cancer. 
Study number: D-FR-01070-003 
The cohort investigated in this study is part of Master Protocol Ipsen 001 Version 1.0 
encompassing specific sub-studies to evaluate 68Ga-OPS202 as a positron emission 
tomography (PET) imaging product in different types of somatostatin receptor 2 (sstr2)-
positive tumours. 
Number of planned centres: Estimated two specialised centres in Europe  
Planned study period: 
FPI: July 2018 - LPO: December 2019 
Phase of development: Phase II. 
Study type: non-randomised phase II 
Objectives: 
Primary study objective:  
The co-primary objectives of the study are: 
• 
To evaluate the percentage of women with newly diagnosed breast cancer who have 
sstr2 positive lesions that are identified using 68Ga-OPS202 
• 
To define the optimal PET imaging time of 68Ga-OPS202 at 0.5, 1.0 and 2 hours post 
injection, based on detected lesions in adult women with sstr2 positive newly 
diagnosed early or advanced breast cancer. 
Secondary study objectives: 
• 
To further define the optimal uptake time of 68Ga-OPS202 based on quantitative 
maximum standardised uptake value (SUVmax) and other quality parameters 
• 
To describe the safety and tolerability of 68Ga-OPS202 in women with newly 
diagnosed (early or advanced) sstr2 positive breast cancer. 
Exploratory objectives: 
• 
To provide preliminary estimates of the sensitivity of 68Ga-OPS202 PET/computed 
tomography (CT) scan imaging, as well as SUV ratio (SUVmax lesion / SUVmean 
reference tissue) and signal-to-noise ratios (SNR) 
• 
To assess the correlation in terms of number of avid lesions between 
18F-fluorodeoxyglucose (18F-FDG)-PET and 68Ga-OPS202 
• 
To assess the correlation between 68Ga-OPS202 tumour uptake with results from 
immunohistochemistry staining of sstr2. 
Study hypothesis: The uptake of 68Ga-OPS202 does not vary according to PET acquisition 
time within a range of 1.5 hours in subjects with sstr2 positive newly diagnosed breast 
cancer, taking into account the 68Ga decay. 


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Methodology: 
Study design: 
This is a non-randomised phase II study, with an approximately 4-week duration for each 
subject and central review-blinded reader endpoint. 
All subjects will receive a single dose of 68Ga-OPS202 (Investigational Imaging Product; 
IIP), consisting of a peptide mass up to 45 μg, with a radioactivity range of 150-200 MBq. 
68Ga-OPS202 is prepared up to 3 hours prior to administration by 68Ga-radiolabelling of an 
OPS202 radiolabelling kit.  
Three PET acquisitions will be performed at 0.5, 1.0 and 2.0 hours post 68Ga-OPS202 
injection. 18F-FDG-PET scan, which is part of routine clinical diagnosis, will be acquired at 
any time during the study period (including the Screening period), according to the 
investigator site’s standards.  
A single contrast enhanced computed tomography (ceCT) scan is required for the study.  
This can be acquired after either of the two PET scans (18F-FDG-PET or 68Ga-OPS202 post 
the 2-hour acquisition).  Thus, only one ceCT scan is required to minimise radiation dose.  
Low-dose CT scans will be acquired for the other PET scans when the ceCT is not obtained. 
All images (68Ga-OPS202 PET/CT scans, 18F-FDG-PET scan, and ceCT scan) will be sent 
to an imaging core laboratory (ICL) for central blinded reading. 
All decisions regarding subjects’ medical management will be made locally by the treating 
physicians (images read locally for this purpose). The ICL/central readers will only evaluate 
the images for the study endpoints and the information will not be provided to the sites on 
an individual subject basis. 
Duration of participation for a subject:  
Subject participation in the study is estimated to last approximately 4 weeks and will include: 
• 
Visit 1: within a screening period of up to 14 days prior to the 68Ga-OPS202 
administration 
• 
Visit 2 (Day 1): a single intravenous (i.v.) injection of a fixed activity range of 
68Ga-OPS202 followed by PET acquisitions at 0.5, 1 and 2 hours ±10 minutes post 
dosing (see Methodology Section above) 
• 
Visit 3: a follow-up visit at Day 14 (±3 days) for evaluation of safety. 
Within the study an 18F-FDG-PET scan and also a ceCT scan must also be acquired. 
 
 
 
 
 
 
 
 
 
 
 
 
Figure S1. Study Design 


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CT=computed tomography, h=hour, IIP=investigational imaging product, PET=positron emission tomography 
Note: Approximately 54 subjects will be screened to receive IIP to identify 16 sstr2 positive evaluable subject scans. 
Assessments: 
The Screening Visit (Visit 1) will be performed within 14 days prior to the first 
68Ga-OPS202 administration. At Screening, after obtaining written informed consent, the 
investigator will collect all the information required to confirm the subject eligibility 
including medical and surgical history, physical examination and vital signs, laboratory tests 
(haematology, blood chemistry and urinalysis) and tumour histopathology if available. 
Tumour biopsy blocks or slides are required for the evaluation of sstr2 expression by 
immunohistochemistry staining with the anatomical location of the lesion(s) indicated to be 
matched with the 68Ga-OPS202 PET/CT images. 
Subjects’ eligibility will be re-checked by the investigator at Baseline/Day 1 (Visit 2) before 
administration of the IIP. If eligibility is re-confirmed, the subject will receive one injection 
of 68Ga-OPS202 followed by whole body PET imaging at 0.5, 1 and 2 hours after the 
injection of the IIP. An 18F-FDG-PET scan will be acquired at any time during the study 
period (including the Screening period), according to the investigator site’s standards. If the 
18F-FDG-PET scan is performed before the informed consent signature, subject approval is 
required for using this image set. 
A single ceCT scan will be performed according to the site standard procedure for chest, 
abdomen, pelvis and brain. This can be acquired after either of the two PET scans 
(18F-FDG-PET or 68Ga-OPS202 post the 2-hour acquisition). Low-dose CT scans will be 
acquired with PET scans when necessary for attenuation correction. 
Subjects may be hospitalised overnight upon completion of 68Ga-OPS202 PET/CT scans at 
the discretion of the investigator. All subjects (either hospitalised or not) will attend a 
consultation on Day 2 for a physical examination and laboratory tests.  
An End of Study Visit (Visit 3) will take place on Day 14 (±3 days), during which the 
investigator will collect the safety information required by the study protocol. At the end of 
Visit 3, the subject’s participation in the study will end. For any adverse event (AE) 
emerging or worsening during the study that persists beyond Visit 3, the investigator will 
monitor the subject until the AE is resolved or considered stabilised. 


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Independent read of PET/CT images: 
This is a non-randomised open-label study. Independent readers will evaluate 68Ga-OPS202 
PET/CT and 18F-FDG-PET/CT images and will be blinded to the acquisition time of the 
PET scans and CT scans, investigator site and clinical status of the subject, including 
pathology, laboratory, medical history and physical exam findings.  
The independent readers are specialised radiologists and/or nuclear medicine physicians 
who are experienced in reading PET/CT scans. To minimise inter- and intra-reader 
variability in results, the readers will be specifically trained for this protocol. Two readers 
will read 100% of all the images and third will adjudicate any differences. 
Number of subjects planned:  
Considering the estimated prevalence of sstr2 overexpression in breast cancer, it is 
anticipated that a total of approximately 54 subjects will be enrolled in the study for 
68Ga-OPS202 PET/CT imaging, to obtain 16 sstr2 positive breast cancer (BC) evaluable 
subjects. However, when the ICL identifies 16 sstr2 positive evaluable subject scans, with 
a minimum of two subjects with advanced disease, the study will be complete.  
Futility Stopping Rules 
If less than three sstr2 positive evaluable subject scans out of 30 consecutive subjects 
screened with 68Ga-OPS202 PET/CT, or less than 8 out of 50, the study will be stopped.  
The Sponsor may consider stopping subject recruitment and revisit the study design with 
possible termination of the study when justified. 
Diagnosis and criteria for inclusion: 
Following a screening period of up to 2 weeks, eligible subjects will be enrolled in the study 
if they meet all the following inclusion criteria, and none of the following exclusion criteria:  
Inclusion criteria: 
1. 
Women aged 18 years or older  
2. 
Subjects with newly diagnosed (early or advanced) breast cancer  
3. 
Eastern Cooperative Oncology Group (ECOG) performance status ≤2 
4. 
Adequate bone marrow, liver and renal function, with: 
x 
Calculated glomerular filtration rate (GFR): ≥45 mL/min  
x 
Albumin: >30 g/L 
x 
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase (AP): ≤ 5 times upper limit of normal (ULN)  
x 
Bilirubin: ≤3xULN (3x1.1 mg/dL) 
x 
Leukocytes: ≥3x109/L, and neutrophils: ≥ 1x109/L 
x 
Erythrocytes: ≥3.5x1012/L 
x 
Platelets: ≥90x109/L  
5. 
Signed written informed consent prior to any study-related procedures. 
Exclusion criteria: 
1. 
Subjects with resected primary tumour  
2. 
Subjects with confirmed ductal carcinoma in situ 
3. 
Men with breast cancer 


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4. 
Presence of an active infection at screening or history of a serious infection within 
the previous 6 weeks prior to the first 68Ga-OPS202 administration that might 
interfere with the PET and/or CT analysis 
5. 
Subjects who have received any therapy for breast cancer 
6. 
Prior or planned administration of a radiopharmaceutical within 8 half-lives of the 
radionuclide  
7. 
Clinically relevant trauma within 2 weeks prior to first 68Ga-OPS202 administration  
8. 
Any condition that precludes the proper performance of PET and/or CT scan: 
x 
Subjects who are not able to tolerate the CT contrast agent 
x 
Subjects with metal implants or arthroplasty, or any other objects that might 
interfere with the PET and/or CT analysis 
x 
Subjects unable to raise arms for prolonged imaging purposes  
x 
Subjects unable to lie still for the entire imaging time 
x 
Subjects weighing greater than 110 kg (243 lb) 
9. 
Known hypersensitivity to radiolabelled NODAGA (1,4,7-triazacyclononane,1-
glutaric acid-4,7-acetic acid), to Gallium-68, to somatostatin analogue peptide JR11 
or to any of the excipients of 68Ga-OPS202 
10. 
History of, or current active allergic or autoimmune disease, including asthma or any 
condition requiring long-term use of systemic corticosteroids 
11. 
Known human immunodeficiency virus (HIV) or positive serology for HIV, 
hepatitis B or C 
12. 
Administration of another investigational medicinal product within 30 days prior to 
first 68Ga-OPS202 administration 
13. 
Subjects who are pregnant, breast feeding or of childbearing potential not willing to 
practice effective contraceptive techniques during the study treatment period and for 
30 days after the last dose of 68Ga-OPS202 administration; pregnancy test must be 
performed at the start of the study and prior to 68Ga-OPS202 administration 
14. 
Subjects who have any severe and/or uncontrolled medical conditions or other 
conditions that could affect their participation in the study, including any mental 
condition rendering the subject unable to understand the nature, scope, and possible 
consequences of the study, and/or evidence of an uncooperative attitude 
15. 
Subject who experienced a previous cancer (except basocellular carcinoma of the skin 
and/or in situ carcinoma of the cervix/uterus, and/or subjects treated with curative 
intent and free from disease for more than 5 years). 
Test product, dose, mode of administration: 
68Ga-OPS202 (IIP) is an imaging radiopharmaceutical with three main components, namely: 
• 
JR11, an antagonist somatostatin analogue that binds to sstr2 receptors 
• 
NODAGA, a chemical chelator moiety, and 
• 
68Ga, a positron emitter radionuclide, with a half-life of 68 minutes. 
The IIP is a solution for injection prepared prior to administration from a radiolabelling 
"cold" kit and a 68Ge/68Ga-generator. The radiolabelling kit consists of two vials; one 
containing 50 μg lyophilised OPS202 and excipients and a second containing a solution for 


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reconstitution. After QC sampling, the volume to be injected into the subject is withdrawn 
from the IIP vial, containing up to 45 μg OPS202. This volume is determined to obtain the 
target radioactivity dose at the time of administration, taking into account the decay of 68Ga. 
All subjects will receive a single dose of IIP, with 68Ga radioactivity dose of 150-200 MBq, 
as a slow i.v. bolus injected over 1 minute. 
There are no fasting conditions, nor food restrictions that should apply when administering 
68Ga-OPS202 to the subject.  
Duration of treatment: 68Ga-OPS202 will be administered as a slow i.v. bolus injected 
over 1 minute once at Baseline/Day 1 (Visit 2). 
Reference therapy, dose and mode of administration:  
Comparator compound/placebo: 
In this study, there is no comparison with a reference-imaging product. The primary 
statistical analyses will evaluate the differences (if any) between the three different scan 
acquisition timepoints of the 68Ga-OPS202 PET.  
Other treatments: Any medication and/or therapy taken or received by the subject during 
the study, other than the study IIP (68Ga-OPS202), will be considered concomitant 
medication whether or not it is targeting the studied breast tumour. Concomitant treatments 
are to be prescribed, modified, or discontinued at the investigator’s discretion. Subjects must 
be withdrawn from the study, but followed-up when possible for further data collection, if 
at least one of the protocol-prohibited medications/therapies (see above-mentioned 
eligibility criteria) is received by the subjects during the study period up to the end of the 
68Ga-OPS202 PET/CT scan at Visit 2. 
Any addition, change, or discontinuation of concomitant medications should be documented 
as defined in the study protocol. 
Criteria for evaluation (endpoints): 
Efficacy: 
The primary and secondary imaging endpoints will be read by third-party independent 
readers. Co-primary and secondary endpoints will be measured in the primary tumour and 
key organs consisting of liver, lymph nodes, bone, lungs and brain. 
Co-primary efficacy endpoints and evaluation 
• 
Percentage of subjects with sufficiently avid lesion(s) to be identified as a sstr2 
positive lesion. (Avid is defined by the blinded readers at one of the acquisition 
timepoints as an easily identifiable lesion radiologically, where there has been clear 
focal uptake of 68Ga-OPS202 and 1.5-fold or greater uptake than the non-tumoural 
liver and lung parenchyma). 
• 
Differences in the number of lesions detected by 68Ga-OPS202 between the three PET 
acquisition timepoints (0.5, 1 and 2 hours), and reader interpretation of optimal 
image(s) in the primary breast lesions. 
Secondary endpoints and evaluations 
Key secondary endpoint: 
• 
Differences in the number of lesions detected by 68Ga-OPS202 between the three PET 
acquisition timepoints (0.5, 1 and 2 hours), and reader interpretation of optimal 
image(s) in nodular and metastatic lesions. Significant uptake of 68Ga-OPS202 for 
the evaluation of a lesion is an avid lesion defined by the blinded readers at one of 


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the acquisition timepoints as an easily identifiable lesion radiologically, where there 
has been clear focal uptake of 68Ga-OPS202 and 1.5-fold or greater uptake than in the 
non-tumoural liver and lung parenchyma. 
• 
The SUVmean and SUVmax in the primary lesion between each of the three timepoints, 
measured in the most avid lesions (using the 68Ga-OPS202 scans).  This is assessed 
by the tumour-to-background ratio in the primary tumour and each of the major 
anatomic sites (liver, lymph nodes, bone, lungs and brain); the background consists 
of non-tumoural liver parenchyma or aortic blood where sufficient liver is not 
available. Identification of lesions to be used will be made by one of the two primary 
readers.  
Other secondary endpoints: 
• 
Differences in relative lesion counts as a ratio of the number of lesions detected by 
68Ga-OPS202 at 0.5, 1 and 2 hours post dose respectively, compared to the number 
of lesions assessed by standard-of-truth (descriptive analyses). The standard-of-truth 
is the 18F-FDG-PET scan images acquired at any time during the study period 
(including the Screening period). This will be calculated by (number of lesions 
detected by 68Ga-OPS202) / (number of lesions detected by 18F-FDG-PET). 
• 
Differences of absolute number of lesions between the three PET acquisition 
timepoints detected in each of the following anatomic sites: 
- 
Lymph nodes  
- 
Liver  
- 
Axial/appendicular skeleton  
- 
Lungs 
- 
Brain 
The second co-primary and appropriate secondary endpoints will also be evaluated on a 
MBq/kg of body weight. 
The secondary endpoints will be summarised by each of the three PET acquisition 
timepoints (0.5, 1 and 2 hours). 
Exploratory endpoints: 
• 
Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging of breast cancer 
expressing sstr2 positive by both subject-based and lesion-based analysis compared 
to standard-of-truth 
• 
SNR calculated from lesion-free volume of interest (VOI) in the liver: 
SUVmean/SUVSD at the three PET acquisition timepoints. 
• 
Estimated correlation in terms of number of avid lesions between 68Ga-OPS202 PET 
at the agreed “optimum timepoint” and 18F-FDG-PET.  
• 
Estimated correlation between 
68Ga-OPS202 PET uptake and results of 
immunohistochemistry staining of sstr2 of the primary tumour. 
Further details on efficacy endpoints are described in the Imaging Review Charter (IRC). 


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Statistical methods: 
Method of randomisation:  
There is no randomisation in the design of the present study. However, the image 
presentation to the central readers will be performed in a blinded manner; thus, the readers 
will be blinded to the image sequence. 
Sample size and power considerations:   
It is anticipated that a total of approximately 54 subjects will be enrolled in the study for 
68Ga-OPS202 PET/CT imaging, to obtain around 16 sstr2 positive BC evaluable subjects. 
Considering the estimated prevalence of sstr2 overexpression in breast cancer, the overall 
number of subjects to be screened with 68Ga-OPS202 in the study will be over 50. However, 
when the ICL identifies 16 sstr2 positive evaluable subjects, with a minimum of two 
subjects with advanced disease, the study will be complete. 
This estimation of 16 sstr2 positive BC evaluable subjects is considered appropriate for a 
descriptive analysis and it is not based on a formal statistical sample size calculation. In the 
event that a subject misses an imaging exam and/or measurement relevant to the primary 
and key secondary endpoints, an additional subject will be recruited to ensure an adequate 
sample size in the sstr2 positive BC evaluable set.  
Statistical analysis: 
The analysis will be descriptive and no formal statistical tests are planned for the primary 
and secondary endpoints. Mean, standard deviation, median and ranges will be estimated. 
The primary endpoint and secondary tumour-to-background ratio and SUVmax endpoints’ 
analyses will be performed.  
Overall differences among the three acquisition timepoints will be analysed. 
Interim analysis: 
No interim analysis is planned for this study.  
 


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TABLE OF CONTENTS 
INVESTIGATOR’S AGREEMENT ...................................................................................... 2 
TABLE OF CONTENTS ....................................................................................................... 13 
LIST OF ABBREVIATIONS ................................................................................................ 18 
1 
BACKGROUND INFORMATION ............................................................................ 21 
1.1 
Introduction ................................................................................................................... 21 
1.2 
Name and Description of Investigational Imaging Product ...................................... 21 
1.3 
Findings from Nonclinical and Clinical Studies ......................................................... 21 
1.4 
Selection of Investigational Imaging Product and Dosages ...................................... 23 
1.5 
Compliance Statement .................................................................................................. 23 
1.6 
Population to Be Studied .............................................................................................. 23 
2 
PURPOSE OF THE STUDY AND STUDY OBJECTIVES ..................................... 24 
2.1 
Purpose of the Study ..................................................................................................... 24 
2.2 
Study Objectives ........................................................................................................... 24 
2.3 
Study Hypothesis ........................................................................................................... 24 
3 
STUDY DESIGN ........................................................................................................... 25 
3.1 
General Design and Study Schema ............................................................................. 25 
3.2 
Primary and Secondary Endpoints and Evaluations ................................................ 26 
3.2.1 
Primary Efficacy Endpoint and Evaluation .............................................. 26 
3.2.2 
Secondary Endpoints and Evaluations ...................................................... 26 
3.2.2.1 
Key Secondary Endpoint .............................................................................. 26 
3.2.2.2 
Other Secondary Endpoints ......................................................................... 27 
3.2.3 
Exploratory Endpoints ................................................................................ 27 
3.2.4 
Safety Endpoints and Evaluations ............................................................. 27 
3.3 
Randomisation and Blinding ....................................................................................... 28 
3.4 
Maintenance of Randomisation and Blinding ............................................................ 28 
3.5 
Study Imaging Product and Dosage ............................................................................ 28 
3.6 
Study Duration .............................................................................................................. 29 
3.7 
Stopping Rules and Discontinuation Criteria ............................................................ 29 
3.8 
Source Data Recorded on the Case Report Form ...................................................... 30 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS ............................................. 31 
4.1 
Inclusion Criteria .......................................................................................................... 31 
4.2 
Exclusion Criteria ......................................................................................................... 31 
4.3 
Rationale for Inclusion/Exclusion Criteria ................................................................. 32 
4.4 
Subject Withdrawal Criteria and Procedures ........................................................... 32 
5 
STUDY PROCEDURES .............................................................................................. 33 
5.1 
Study Schedule .............................................................................................................. 33 
5.2 
Study Visits .................................................................................................................... 34 
5.2.1 
Procedures for Screening and Enrolment (Visit 1) ................................... 34 


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5.2.2 
Procedures Before Study IIP Administration (Day 1, Visit 2 Pre-dose) ... 35 
5.2.3 
Dosing (Day 1, Visit 2) ................................................................................ 35 
5.2.4 
Procedures after IIP Administration (Day 1 and Day 2, Visit 2 Post-dose)
 ...................................................................................................................... 35 
5.2.5 
End of Study Visit or Early Withdrawal Visit (Day 14±3, Visit 3) ............ 36 
6 
INVESTIGATIONAL IMAGING PRODUCT AND DOSING OF SUBJECTS ... 36 
6.1 
Investigational Imaging Product Preparation and Radiolabelling Kit, Storage 
and Accountability ........................................................................................................ 36 
6.1.1 
Investigational Imaging Product and Radiolabelling Kit Storage and 
Security ........................................................................................................ 36 
6.1.1.1 
Spillage ........................................................................................................ 36 
6.1.2 
Investigational Imaging Product Preparation ........................................... 37 
6.1.3 
Investigational Imaging Product and Radiolabelling Kit Accountability 37 
6.1.4 
Investigational Imaging Product (68Ga-OPS202) ...................................... 37 
6.2 
Study Drugs Administered ........................................................................................... 38 
6.3 
Concomitant Medication/Therapy .............................................................................. 38 
6.4 
Procedures for Monitoring Subject Compliance ....................................................... 38 
7 
ASSESSMENT OF EFFICACY .................................................................................. 39 
7.1 
Eligible and Evaluable Subjects .................................................................................. 41 
8 
ASSESSMENT OF SAFETY ....................................................................................... 42 
8.1 
Adverse Events .............................................................................................................. 42 
8.1.1 
Categorisation of Adverse Events ............................................................... 42 
8.1.1.1 
Intensity Classification ................................................................................. 42 
8.1.1.2 
Causality Classification ............................................................................... 43 
8.1.1.3 
Assessment of Expectedness ......................................................................... 43 
8.1.1.4 
Laboratory Test Abnormalities .................................................................... 43 
8.1.1.5 
Abnormal Physical Examination Findings .................................................. 43 
8.1.1.6 
Other Investigation Abnormal Findings ...................................................... 43 
8.1.2 
Recording and Follow up of Adverse Events ............................................. 43 
8.1.3 
Reporting of Serious Adverse Events ......................................................... 44 
8.1.4 
Pregnancy .................................................................................................... 45 
8.1.5 
Deaths .......................................................................................................... 46 
8.1.6 
Discontinuation/Withdrawal due to Adverse Events/Serious Adverse 
Events .......................................................................................................... 46 
8.2 
Clinical Laboratory Tests ............................................................................................ 46 
8.2.1 
Haematology ................................................................................................ 46 
8.2.2 
Blood Biochemistry ..................................................................................... 47 
8.2.3 
Urinalysis ..................................................................................................... 47 
8.2.4 
Pregnancy Test ............................................................................................ 47 
8.2.5 
Putative Antibody Testing ........................................................................... 47 


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8.2.6 
Other Clinical Laboratory Tests ................................................................. 47 
8.3 
Physical Examination ................................................................................................... 47 
8.4 
Vital Signs ...................................................................................................................... 47 
8.5 
Electrocardiography ..................................................................................................... 47 
9 
ASSESSMENTS OF PHARMACOKINETICS/PHARMACODYNAMICS .......... 49 
10 
EXPLORATORY BIOMARKERS AND BIOBANKING ....................................... 49 
11 
STATISTICS ................................................................................................................. 50 
11.1 Analyses Populations .................................................................................................... 50 
11.1.1 
Populations Analysed .................................................................................. 50 
11.1.2 
Subject Allocation and Reasons for Exclusion from the Analyses ........... 50 
11.2 Sample Size Determination .......................................................................................... 50 
11.3 Significance Testing and Estimations ......................................................................... 50 
11.4 Statistical/Analytical Methods ..................................................................................... 51 
11.4.1 
Demographic and Other Baseline Characteristics .................................... 51 
11.4.2 
Homogeneity of Treatment Groups ............................................................ 51 
11.4.3 
Subject Disposition and Withdrawals ......................................................... 51 
11.4.4 
Efficacy Evaluation ..................................................................................... 51 
11.4.5 
Adjustment for Country/Centre Effect ....................................................... 52 
11.4.6 
Safety Evaluation ........................................................................................ 52 
11.5 Subgroup Analyses ....................................................................................................... 53 
11.6 Interim Analyses ........................................................................................................... 53 
12 
DIRECT ACCESS TO SOURCE DATA AND DOCUMENTS ............................... 54 
13 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................... 55 
13.1 Protocol Amendments and Protocol Deviations and Violations ............................... 55 
13.1.1 
Protocol Amendments ................................................................................. 55 
13.1.2 
Protocol Deviations ..................................................................................... 55 
13.2 Information to Study Personnel .................................................................................. 56 
13.3 Study Monitoring .......................................................................................................... 56 
13.4 Audit and Inspection .................................................................................................... 57 
13.5 Data Quality Assurance ................................................................................................ 57 
14 
ETHICS ......................................................................................................................... 58 
14.1 Compliance with Good Clinical Practice and Ethical Considerations .................... 58 
14.2 Informed Consent for Participation in the Study ...................................................... 58 
14.3 Health Authorities and Independent Ethics Committees/Institutional Review 
Boards ............................................................................................................................ 59 
14.4 Confidentiality Regarding Study Subjects ................................................................. 59 
15 
DATA HANDLING AND RECORD KEEPING ....................................................... 60 
15.1 Data Recording of Study Data ..................................................................................... 60 
15.2 Data Management ......................................................................................................... 60 


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15.3 Record Archiving and Retention ................................................................................. 61 
16 
FINANCING AND INSURANCE ............................................................................... 62 
16.1 Contractual and Financial Details ............................................................................... 62 
16.2 Insurance, Indemnity and Compensation .................................................................. 62 
17 
REPORTING AND PUBLICATIONS OF RESULTS ............................................. 63 
17.1 Publication Policy ......................................................................................................... 63 
17.2 Clinical Study Report ................................................................................................... 63 
18 
REFERENCES .............................................................................................................. 64 
19 
LIST OF APPENDICES .............................................................................................. 65 
 


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LIST OF TABLES 
Table 1 
List of Protocol Amendments ............................................................................... 4 
Table 2 
Radiochemical Characteristics of 68Ga .............................................................. 21 
Table 3 
Study Procedures and Assessments ................................................................... 33 
 
LIST OF FIGURES 
Figure 1 
Study Design ........................................................................................................ 26 
 


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LIST OF ABBREVIATIONS 
ABBREVIATION 
Wording Definition  
βHCG 
Beta human chorionic gonadotropin 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BC 
Breast cancer 
bpm 
Beats per minute 
BUN 
Blood urea nitrogen 
CA 
Competent Authorities 
CFR 
Code of Federal Regulations (United States of America) 
CRF 
Case report form 
CRO 
Contract research organisation 
CT 
Computed tomography 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
eCRF 
Electronic case report form 
EU 
European Union 
FDA 
Food and Drug Administration 
18F-FDG 
18F-fluorodeoxyglucose 
GCP 
Good Clinical Practice 
GEP-NETs 
Gastroenteropancreatic neuroendocrine tumours 
GGT 
Gamma-glutamyl transferase 
GMP 
Good Manufacturing Practice 
HBsAg 
Hepatitis B surface antigen 
HCG 
Human chorionic gonadotropin 
HER2 
Human epidermal growth factor receptor 2 
HIV 
Human immunodeficiency virus 
%IA/g 
Percentage injected activity per gram of tissue 
ICH 
International Conference on Harmonisation 
ICL 
Imaging core laboratory 
IEC 
Independent ethics committee 
IIP 
Investigational imaging product  


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ABBREVIATION 
Wording Definition  
INN 
International nonproprietary name 
IND 
Investigational New Drug 
IRB 
Institutional review board 
IRC 
Imaging review charter 
i.v. 
Intravenous 
LDH 
Lactate dehydrogenase 
max 
Maximum 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
min 
Minimum 
MTD 
Maximum Tolerated Dose (Dosage) 
NA 
Not applicable 
NCI-CTC 
National Cancer Institute – Common Toxicity Criteria 
NET 
Neuroendocrine tumour 
NOAEL 
No observable adverse effect level 
NOS 
Not otherwise specified 
PP 
Per protocol 
PET 
Positron emission tomography 
PT 
Preferred term 
RBC 
Red blood cell(s) 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SAS® 
Statistical Analysis System® 
SD 
Standard deviation 
SDV 
Source document verification 
SE 
Standard Error 
SmPC 
Summary of Product Characteristics 
SNR 
Signal-to-noise ratio 
SOP 
Standard Operating Procedure 
SPECT 
Single-photon emission computed tomography 
sstr 
Somatostatin receptor 
sstr2 
Somatostatin receptor subtype 2 


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ABBREVIATION 
Wording Definition  
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
SUVmax 
Maximum standardised uptake value 
SUVmean 
Mean standardised uptake value 
TEAE 
Treatment emergent adverse event 
ULN 
Upper limit of normal range 
US(A) 
United States (of America) 
WBC 
White blood cell(s) 
WHO 
World Health Organisation 
WHO-DD 
World Health Organization (WHO) drug dictionary 


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1 
BACKGROUND INFORMATION 
1.1 
 Introduction 
Somatostatin-based radiolabelled agonistic peptides have been successfully introduced into the 
clinic for targeted imaging of somatostatin receptor (sstr)-positive neuroendocrine tumours 
(NETs), especially of the clinically most relevant subtype sstr2. Currently, three 
somatostatin-based radiolabelled peptide analogues are approved in the United States and/or 
Europe: namely, 111In pentetreotide (Octreoscan™), which is based on gamma rays, visualizing 
sstr-positive tumours in whole body single-photon emission computed tomography (SPECT) 
[1], 68Ga-DOTA-TATE (NETSPOT®), and 68Ga-DOTA-TOC (Somakit TOC) used with 
positron emission tomography (PET) imaging that provides several advantages over SPECT 
such as temporal and spatial resolution, reduced radiation burden and diminished examination 
time [2, 3].  
1.2 
 Name and Description of Investigational Imaging Product 
OPS202 (satoreotide trizoxetan) is a new generation somatostatin analogue (antagonist) 
compound with potential superior tumour detection as a consequence of the availability of more 
binding sites for both active and inactive sstr2. It consists of the small somatostatin analogue 
JR11 conjugated to the strong cyclical chelating agent NODAGA (1,4,7-triazacyclononane,1-
glutaric acid-4,7-acetic acid), which is radiolabelled with the radioactive isotope gallium-68 
(68Ga) to produce 68Ga-OPS202. This complex (68Ga-OPS202) is being developed as a PET 
imaging agent for the detection of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) 
in patients. 
68Ga is a short-lived (half-life: 68 min) positron-emitting isotope generated from decay of the 
parent isotope germanium-68 (68Ge, half-life: 271 days). In the clinic (radiopharmacy), it can 
be derived from a 68Ge/68Ga-generator. One of the main advantages of 68Ga is its 
cyclotron-independent availability, providing an inexpensive, decentralised and convenient 
alternative to cyclotron-generated isotopes. Further key radiochemical characteristics of 68Ga 
are summarised in Table 2. 
Table 2 
Radiochemical Characteristics of 68Ga 
68Ga physical half-
life T1⁄2 
Decay product 
Maximum 
positron energy 
Maximum linear 
range 
Median linear 
range 
68 min 
68Zn 
1.89 MeV 
9.1 mm 
1.9 mm 
 
68Ga-OPS202 is being developed as a PET diagnostic imaging agent for sstr2 positive tumours.  
A more detailed description of the product is given in Section 3.4. 
1.3 
Findings from Nonclinical and Clinical Studies 
In mice bearing sstr2 expressing tumours, 68Ga-OPS202 showed a higher tumour uptake than 
the reference imaging radiopharmaceutical 68Ga-DOTATATE (30.7±1.6 percentage injected 
activity per gram of tissue (%IA/g) versus 17.8±2.2 %IA/g, respectively, p<0.05 at 1 hour after 
injection), whereas tumour-to-kidney ratio was comparable for both radiolabelled peptides, 
suggesting a potential clinical benefit of the antagonist peptide 68Ga-OPS202 over the agonist 
peptide 68Ga-DOTA-TATE. Tumour-to-muscle ratio was in favour of 68Ga-OPS202 as 
compared to 68Ga-DOTA-TATE (153.5 versus 50.8, respectively, at 1 hour post-injection) as 
well as tumour-to-blood and tumour-to-liver ratios at 2 hours post-injection. 


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No relevant toxicological effect was observed in OPS202 treated male and female rats for all 
investigated parameters (mortality, clinical signs, body weight, food consumption, clinical 
pathology, organ weights, macroscopic and microscopic examinations). The dose of 
1.43 mg/kg OPS202 given once intravenously (i.v.) is within the no-observed-adverse-effect-
level (NOAEL). Of note, the intended clinical mass dose administered to subjects is a maximum 
of 50 μg, which corresponds to 0.71 μg/kg for a 70-kg subject. 
Two anecdotal reported cases under compassionate use at the Zentralklinik Bad Berka provided 
preliminary data supporting the safety and efficacy of 68Ga-OPS202. These two subjects with a 
diagnosis of NETs were imaged with radiolabelled sstr2 antagonist 68Ga-OPS202, which was 
compared to 68Ga-DOTA-TOC imaging. In the first subject, significantly higher uptake with 
68Ga-OPS202 compared to 68Ga-DOTA-TOC was detected in the large primary pancreatic 
tumour (maximum standardised uptake value (SUVmax) of 21% or higher) and additionally two 
osseous metastases were detected which were not seen in the 68Ga-DOTA-TOC PET/CT 
examination in this subject. In the second subject, three more liver metastases were detected by 
68Ga-OPS202 compared to detection by 68Ga-DOTA-TOC. This may have been due to the 
favourably higher tumour-to-liver uptake ratio with 68Ga-OPS202 imaging when compared to 
the 68Ga-DOTA-TOC evaluation. These imaging results encouraged further investigation of 
68Ga-OPS202 being a promising radiopharmaceutical tracer and potentially superior to the 
standard Octreoscan™ or the newly approved 68Ga-DOTA-TATE and 68Ga-DOTA-TOC in the 
diagnosis of GEP-NET lesions. 
A single-centre, open-label, dose-finding, single-dosing study (Study OPS-B-001) was 
conducted to evaluate safety and tolerance, as well as biodistribution, dosimetry and 
preliminary efficacy of two single 68Ga-OPS202 peptide mass doses (15±5 and 50±15 μg), each 
labelled with the same radioactivity dose of 200 megabecquerels (MBq) ±25% of 68Ga tracer 
(as initially described in the study protocol) for the diagnostic imaging of sstr2 positive 
GEP-NETs using PET/CT. 
Six out of 12 subjects (50.0%) experienced 11 adverse events (AEs), all of which were assessed 
by the investigator as being non-serious. Most of the AEs were mild in intensity and were 
considered by the investigator as unlikely or not related to the Investigational Imaging Product 
(IIP). Three AEs in two subjects were assessed as possibly related to 68Ga-OPS202: 
eosinophilia, rash and diarrhoea. The most frequently reported AEs were urinary tract infection 
(n=2) and fatigue (n=2); these AEs were considered unlikely or not related to the IIP. 
The study also showed promising preliminary efficacy results, with the most frequently 
identified lesions being malignant lesions in the liver. In all scans (somatostatin receptor 1-hour 
scan performed within 6 months before start of the study [pre-baseline] and two 68Ga-OPS202 
dose 1-hour scans), malignant liver lesions were detected in nine subjects. Malignant lymph 
node lesions were identified in seven subjects in the pre-baseline somatostatin receptor 1-hour 
scan and eight subjects in the 68Ga-OPS202 1-hour scans. 
The detection rate of malignant lesions considering all organs/tissues (total) was significantly 
higher in the 68Ga-OPS202 1-hour scans than in the pre-baseline somatostatin receptor 1-hour 
scan (p≤0.016). This was based on the significantly higher number of liver lesions detected in 
the 68Ga-OPS202 1-hour scans compared to the somatostatin receptor 1-hour scan (p≤0.012). 
No significant difference was seen between the pre-baseline somatostatin receptor 1-hour scan 
and the 68Ga-OPS202 1-hour scans with regard to the detection rate of malignant lymph node 
lesions. 
Further details may be found in the Investigator’s Brochure (IB). 


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1.4 
Selection of Investigational Imaging Product and Dosages 
In an on-going study in subjects with NETs (Study D-FR-01070-002), two target peptide mass 
dose ranges (5-20 μg and 30-45 μg) and three radioactivity dose ranges are being investigated: 
• 
40-80 MBq 
• 
100-140 MBq 
• 
160-200 MBq 
The present study will add information on the optimal PET/CT acquisition time using the 
highest radioactivity range. Although there is over-expression of sstr2 in many breast cancer 
tumours, this level is lower than seen in subjects with NETs.  Therefore, it is anticipated that in 
order to obtain optimal images with 68Ga-OPS202 in non-NETs subjects, the highest injected 
radioactivity dose range would be appropriate. 
A more detailed description of administration procedures is given in Section 6.1.  
1.5 
Compliance Statement 
The study will be conducted in compliance with independent ethics committees (IECs), 
informed consent regulations, the Declaration of Helsinki and International Conference on 
Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. Any episode of noncompliance 
will be documented. 
In addition, the study will adhere to all local regulatory requirements.  
Before initiating a study, the investigator/institution should have written and dated 
approval/favourable opinion from the IEC for the study protocol/amendment(s), written 
informed consent form, any consent form updates, subject emergency study contact cards, 
subject recruitment procedures (e.g. advertisements), any written information to be provided to 
subjects and a statement from the IEC that they comply with GCP requirements. The IEC 
approval must identify the protocol version as well as the documents reviewed. 
1.6 
Population to Be Studied 
Several types of tumours other than NETs express sstr2 making the imaging of these tumours 
with peptide receptor radionuclide such as 68Ga-OPS202 possible. This study will enrol adult 
female subjects with newly diagnosed early or advanced breast cancer to detect those 
expressing sstr2.  
To identify the evaluable subjects for the analysis of the primary endpoint, tumours/metastases 
expressing sstr2 will be identified and documented through the lesion uptake of the diagnostic 
compound (68Ga-OPS202). Only subjects showing tumour 68Ga-OPS202 uptake (avid lesion) 
in target tissues (primary tumour, lymph nodes and/or metastases) higher than non-tumoural 
liver parenchyma by PET imaging will be selected for the comparison of images at different 
acquisition timepoints. 


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2 
PURPOSE OF THE STUDY AND STUDY OBJECTIVES 
2.1 
Purpose of the Study 
68Ga-OPS202 PET/CT has been solely investigated in patients with NETs. Non-NETs 
expressing sstr2 may have a different level of receptors expression raising the question of a 
possible difference in terms of optimal uptake time. This phase II study aims to estimate firstly 
the percentage of female subjects with newly diagnosed breast cancer who have sstr2 positive 
lesions using 68Ga-OPS202, secondly in those subjects with sstr2 positive tumours, the optimal 
PET acquisition time based on detected number of lesions and tumour to background ratio in 
subjects with sstr2 positive breast cancer. The study will also expand the evaluation of 68Ga-
OPS202 safety in patients with non-NETs expressing sstr2. 
2.2 
Study Objectives 
The co-primary objectives of the study are: 
• 
To evaluate the percentage of women with newly diagnosed breast cancer who have sstr2 
positive lesions that are identified using 68Ga-OPS202 
• 
To define the optimal PET imaging time of 68Ga-OPS202 at 0.5, 1.0 and 2 hours post 
injection, based on detected lesions in adult women with sstr2 positive newly diagnosed 
early or advanced breast cancer. 
The secondary objectives of the study are as follows: 
• 
To further define the optimal uptake time of 68Ga-OPS202 based on quantitative SUVmax 
and other quality parameters  
• 
To describe the safety and tolerability of 68Ga-OPS202 in women with newly diagnosed 
(early or advanced) sstr2 positive breast cancer 
The exploratory objectives of the study are as follows: 
• 
To provide preliminary estimates of the sensitivity of 68Ga-OPS202 PET/CT scan 
imaging, as well as SUV ratio (SUVmax lesion/SUVmean reference tissue) and signal-to-
noise ratios (SNR) 
• 
To assess the correlation in terms of number of avid lesions between 
18F-fluorodeoxyglucose (18F-FDG)-PET and 68Ga-OPS202 
• 
To assess the correlation between 68Ga-OPS202 tumour uptake with results from 
immunohistochemistry staining of sstr2. 
2.3 
Study Hypothesis 
The uptake of 68Ga-OPS202 does not vary according to PET acquisition time within a range of 
1.5 hours in subjects with sstr2 positive newly diagnosed breast cancer, taking into account the 
68Ga decay. 


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3 
STUDY DESIGN 
3.1 
General Design and Study Schema 
This is a non-randomised phase II study, with an approximately 4-week duration for each 
subject and central review-blinded reader endpoint. 
All subjects will receive a single dose of 68Ga-OPS202 (IIP), consisting of a peptide mass up to 
45 μg, with a radioactivity range of 150-200 MBq. 68Ga-OPS202 is prepared up to 3 hours prior 
to administration by 68Ga-radiolabelling of an OPS202 radiolabelling kit.  
Three PET images will be acquired at 0.5, 1.0 and 2.0 hours post 68Ga-OPS202 injection.  
18F-FDG-PET scan, which is part of routine clinical diagnosis, will be acquired at any time 
during the study period (including the Screening period), according to the investigator site’s 
standards. 
A single ceCT scan is required for the study.  This can be acquired following either of the two 
PET scans (FDG-PET or 68Ga-OPS202 post the 2-hour acquisition).  Only one ceCT scan is 
required to minimise radiation dose.  Low-dose CT scans will be acquired for the other PET 
scans when the ceCT is not obtained. For the 68Ga-OPS202 PET scan a single low dose CT scan 
is preferred for the 0.5 and 1.0-hour post dosing acquisitions. 
All images (68Ga-OPS202 PET/CT scans, 18F-FDG-PET/CT scan, and ceCT scan) will be sent 
to an imaging core laboratory (ICL) for central blinded reading.  See Section 7 and the Imaging 
Review Charter (IRC) for further details. 
All decisions regarding subjects’ medical management will be made locally by the treating 
physicians (images read locally for this purpose). The ICL/central readers will only evaluate 
the images for the study endpoints and the information will not be provided to the sites on an 
individual subject basis. 
The Screening Visit (Visit 1) will be performed within 14 days prior to the 68Ga-OPS202 
administration. At Screening, after obtaining written informed consent, the investigator will 
collect all the information required to confirm the subject eligibility including medical and 
surgical history, physical examination and vital signs, laboratory tests (haematology, blood 
chemistry and urinalysis) and tumour histopathology if available. Tumour biopsy, which is not 
a prerequisite for inclusion, is routinely performed for confirmation and staging of the disease, 
as well as classification according to hormone receptor status and human epidermal growth 
factor receptor 2 (HER2) status. For the study, the collection of an archived tumour sample (a 
block is preferred over paraffin embedded slides) is required for the evaluation of sstr2 
expression by immunohistochemistry staining.  
Subjects’ eligibility will be re-checked by the investigator at Baseline/Day 1 (Visit 2) before 
administration of the IIP. If eligibility is re-confirmed, the subject will receive one injection of 
68Ga-OPS202 followed by whole body PET acquisition at 0.5, 1 and 2 hours after the injection 
of the IIP. A single ceCT scan will be performed according to the site standard procedure for 
chest, abdomen, pelvis and brain. This can be acquired after either of the two PET scans 
(18F-FDG-PET or 68Ga-OPS202 post the 2-hour acquisition). Low-dose CT scans will be 
acquired with PET scans when necessary for attenuation correction. 
Subjects may be hospitalised overnight upon completion of the 68Ga-OPS202 PET/CT scans at 
the discretion of the investigator. All subjects (either hospitalised or not) will attend a 
consultation on Day 2 for vital signs and laboratory tests. Also an 18F-FDG-PET scan and ceCT 
scan will be arranged if not already acquired. 


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An End of Study Visit (Visit 3) will take place on Day 14 (±3 days), during which the 
investigator will collect the safety information required by the study protocol (see Criteria of 
safety evaluation below). At the end of Visit 3, the subject’s participation in the study will end. 
For any adverse event (AE) emerging or worsening during the study that persists beyond 
Visit 3, the investigator will monitor the subject until the AE is resolved or considered 
stabilised. 
Study design scheme is presented in Figure 1. 
Figure 1 Study Design 
 
CT=computed tomography, h=hour, IIP=investigational imaging product, PET=positron emission tomography 
Note: Approximately 54 subjects will be screened to receive IIP to identify 16 sstr2 positive evaluable subject scans. 
 
3.2 
Primary and Secondary Endpoints and Evaluations 
The primary and secondary imaging endpoints will be read by third-party independent readers. 
Co-primary and secondary endpoints will be measured in the primary tumour and key organs 
consisting of liver, lymph nodes, bone, lungs and brain. 
3.2.1 
Primary Efficacy Endpoint and Evaluation 
• 
Percentage of subjects with sufficiently avid lesion(s) to be identified as a sstr2 positive 
lesion. (Avid is defined by the blinded readers at one of the acquisition timepoints as an 
easily identifiable lesion radiologically, where there has been clear focal uptake of 
68Ga-OPS202 and 1.5-fold or greater uptake than the non-tumoural liver and lung 
parenchyma). 
• 
Differences in the number of lesions detected by 68Ga-OPS202 between the three PET 
acquisition timepoints (0.5, 1 and 2 hours), and reader interpretation of optimal image(s) 
in the primary breast lesions. 
3.2.2 
Secondary Endpoints and Evaluations 
3.2.2.1 
Key Secondary Endpoint 
• 
Differences in the number of lesions detected by 68Ga-OPS202 between the three PET 
acquisition timepoints (0.5, 1 and 2 hours), and reader interpretation of optimal image(s) 
in nodular and metastatic lesions. Significant uptake of 68Ga-OPS202 for the evaluation 


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of a lesion is an avid lesion defined by the blinded readers at one of the acquisition 
timepoints as an easily identifiable lesion radiologically, where there has been clear focal 
uptake of 68Ga-OPS202 and 1.5-fold or greater uptake than in the non-tumoural liver 
and lung parenchyma. 
• 
The SUVmean and SUVmax in the primary lesion between each of the three timepoints, 
measured in the most avid lesions (using the 68Ga-OPS202 scans).  This is assessed by 
the tumour-to-background ratio in the primary tumour and each of the major anatomic 
sites (liver, lymph nodes, bone, lungs and brain); the background consists of 
non-tumoural liver parenchyma or aortic blood where sufficient liver is not available. 
Identification of lesions to be used will be made by one of the two primary readers.  
3.2.2.2 
Other Secondary Endpoints 
• 
Differences in relative lesion counts as a ratio of the number of lesions detected by 
68Ga-OPS202 at 0.5, 1 and 2 hours post dose respectively, compared to the number of 
lesions assessed by standard-of-truth (descriptive analyses). The standard-of-truth is the 
18F-FDG-PET/CT scan images acquired at any time during the study period (including 
the Screening period). This will be calculated by (number of lesions detected by 
68Ga-OPS202) / (number of lesions detected by 18F-FDG-PET). 
• 
Differences of absolute number of lesions between the three PET acquisition timepoints 
detected in each of the following anatomic sites: 
- 
Lymph nodes  
- 
Liver  
- 
Axial/appendicular skeleton  
- 
Lungs 
- 
Brain 
The primary and appropriate secondary endpoints will also be evaluated on a MBq/kg of body 
weight. 
The secondary endpoints will be summarised by each of the three PET acquisition timepoints 
(0.5, 1 and 2 hours). 
3.2.3 
Exploratory Endpoints 
• 
Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging of breast cancer expressing 
sstr2 positive by both subject-based and lesion-based analysis compared to standard-of-
truth 
• 
SNR calculated from lesion-free volume of interest (VOI) in the liver: SUVmean/SUVSD 
at the three PET acquisition timepoints 
• 
Estimated correlation in terms of number of avid lesions between 68Ga-OPS202 PET at 
the agreed “optimum timepoint” and 18F-FDG-PET  
• 
Estimated 
correlation 
between 
68Ga-OPS202 PET 
uptake 
and 
results 
of 
immunohistochemistry staining of sstr2 of the primary tumour. 
For further details on efficacy endpoints, refer to Section 7 and the IRC. 
3.2.4 
Safety Endpoints and Evaluations 
The investigator will report the occurrence of any AE throughout the study and vital signs 
(including blood pressure and heart rate) measurements at each visit: Screening Visit (Visit 1; 
Day -14 to -1), Visit 2 (Day 1), Visit 2 (Day 2) and End of Study/Early Withdrawal Visit 


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(Visit 3). Clinically significant abnormalities in laboratory tests (serum chemistry, 
haematology, and urinalysis) measurements will be reported at Screening Visit, Visit 2 (Day 2) 
and End of Study/Early Withdrawal Visit. Physical examination findings and body weight 
measurements will be reported at Screening Visit, Visit 2 (Day 1) and End of Study/Early 
Withdrawal Visit. The electrocardiogram (ECG) findings are to be recorded at the Screening 
Visit and the End of Study/Early Withdrawal Visit. Relevant medical history and concomitant 
medications/therapies will also be recorded throughout the study. 
The following safety endpoints will be evaluated: 
• 
Proportion of subjects experiencing at least one AE of any grade according to the 
National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-
CTCAE) version 5.0, including any serious AEs including suspected unexpected serious 
adverse reactions (SUSARs); all AEs will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA) system organ class (SOC) and preferred term (PT) (as 
per most recent version) 
• 
Proportion of subjects experiencing at least one AE of grade ≥3 according to NCI 
CTCAE.   
• 
Clinically significant changes in physical examination, vital signs, ECG and laboratory 
findings, which will be recorded by the investigator as AEs. 
3.3 
Randomisation and Blinding 
This is an open-label non-randomised study. However, the independent readers will evaluate 
68Ga-OPS202 PET/CT and 18F-FDG-PET/CT images and will be blinded to the acquisition time 
of the PET scans and CT scans, investigator site and clinical status of the subject, including 
pathology, laboratory, medical history and physical exam findings.  
Independent readers are specialised radiologists and/or nuclear medicine physicians who are 
experienced in reading PET/CT scans. To minimise inter- and intra-reader variability in results, 
the readers will be specifically trained for this protocol. Two readers will read 100% of all the 
images and third will adjudicate any differences. See the Imaging Review Charter (IRC). 
3.4 
Maintenance of Randomisation and Blinding 
All blinding is handled by the ICL and described in the IRC. 
3.5 
Study Imaging Product and Dosage 
The IIP is provided in a sterile two-vial radiolabelling kit constituted of freeze-dried powder 
containing 50 μg non-radiolabelled precursor OPS202 and excipients (Vial A) and the solvent 
for reconstitution (Vial B) to be used prior to radiolabelling. 
The radiolabelling kit must be maintained between + 2 °C and + 8 °C until reconstitution.  
Radiolabelling yields the IIP 68Ga-OPS202 as a solution for injection, placed in a shielding 
secondary container. This shielding container will be labelled according to local requirements 
and identified with a radiolabelling batch number and the subject number. The volume to be 
administered to the subject is withdrawn from the IIP vial. This volume is determined to obtain 
the target radioactivity dose at the time of administration, taking into account the decay of 68Ga. 
All subjects will receive a single dose of 150-200 MBq 68Ga-OPS202 (IIP), as a slow i.v. bolus 
injected over 1 minute. 
A more detailed description of preparation and administration procedures is given in 
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The radiolabelling kit will be packaged and delivered in a sufficient quantity to the 
investigational sites with a delivery note including an acknowledgement of receipt.  
The investigator’s representative will receive:  
• 
For each batch of radiolabelling kit that will be used during the study, a Certificate of 
Compliance and Certificate of Analysis, which reflects the product release statement, 
• 
Material Safety Data Sheet,  
• 
Delivery note including an Acknowledgement of Receipt (AoR), Packaging Order.  
All the labels identifying the radiolabelling kits will be designed in accordance with all 
requirements of Good Manufacturing Practice (GMP) and applicable national laws in force in 
the countries. The label of the radiolabelling kit and the label of lead container will be translated 
into local languages.  
The investigator, or designee, will only dispense IIP to subjects included in this study. Each 
subject will only be given the IIP carrying his/her number. The dispensing for each subject will 
be documented in the eCRF. 
3.6 
Study Duration 
Subject participation in the study will include: 
• 
Visit 1: a screening period up to 14 days prior to IIP administration 
• 
Visit 2: a single i.v. injection of between 150 MBq to 200 MBq of 68Ga OPS202 on Day 1 
followed by PET acquisition at 0.5, 1 and 2 hours ±10 minutes post dosing,  
• 
Visit 3: a follow-up visit at Day 14 (±3 days) for evaluation of safety.  
Within the study an 18F-FDG-PET scan and also a ceCT scan must also be acquired. 
The subject’s participation in the study will be considered to have ended at the time of the last 
visit (Visit 3, at Day 14 ±3 days).  
The overall duration of the study will be approximately 4 weeks for each subject. The study 
will be considered to have started when the first subject has provided signed informed consent.  
The study will be considered to have ended after the last subject has completed the last follow 
up period in the study. 
3.7 
Stopping Rules and Discontinuation Criteria 
During the conduct of the study, SAEs will be reviewed (see Section 8.1.3) as they are reported 
from the study centres to identify safety concerns. A specific site or a given cohort can be 
discontinued or the entire study may be terminated at any time if the sponsor judges it necessary 
for any reason. In that case, all scheduled procedures and assessments for subjects who are still 
in the study will be performed. Some possible reasons for the closure of a study site may 
include: 
• 
failure of the Investigator staff to comply with the protocol or with the GCP guidelines 
• 
safety concerns 
• 
inadequate subject recruitment. 
The study may be terminated by the sponsor at any time. 
A subject may discontinue participation in the study at any time for any reason (e.g. withdrawal 
of consent, AE). The investigator and/or sponsor can withdraw a subject from the study at any 
time for any reason (e.g. protocol deviation as defined in Section 13.1.2, noncompliance with 
the protocol conditions or AE). All cases of discontinuation will be discussed between the 
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Futility Stopping Rule 
If less than three sstr2 positive evaluable subject scans out of 30 consecutive subjects screened 
with 68Ga-OPS202 PET/CT, or less than 8 out of 50, the study will be stopped.  
3.8 
Source Data Recorded on the Case Report Form 
Data will be collected in the eCRF in compliance with FDA 21 CFR Part 11. As required by 
GCP, the sponsor-assigned monitor will verify, by direct reference to the source documents, 
that the data required by the protocol are accurately reported in the eCRF.  
The source documents must, as a minimum, contain a statement that the subject is included in 
a clinical study, the date that informed consent was obtained prior to participation in the study, 
the identity of the study, diagnosis and eligibility criteria, visit dates (with subject status), IIP 
administration, and any AEs and associated concomitant medications. 
As required by ICH GCP Section 6.4.9, if some items are recorded directly in the eCRF and are 
considered as source data, the identification of these data must be documented and agreed 
between the investigator and the sponsor. 
Definition for source data and source documents are given below: 
• 
Source Data: All original records and certified copies of original records of clinical 
findings, observations, or other activities necessary for the reconstruction and evaluation 
of the study. Source data are contained in source documents (original records or certified 
copies). 
• 
Source Documents: Original documents, data and records (e.g. hospital records, clinical 
and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x rays, subject files, and records 
kept at the pharmacy, at the laboratories and at medicotechnical departments involved in 
the clinical study). 
The subject must have consented to their medical records being viewed by the sponsor’s 
authorised personnel, and by local, and possibly foreign, competent authorities (CAs). This 
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4 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Inclusion Criteria 
All subjects must fulfil the following criteria to be included in the study: 
(1) 
Women aged 18 years or older  
(2) 
Subjects with newly diagnosed (early or advanced) breast cancer  
(3) 
Eastern Cooperative Oncology Group (ECOG) performance status ≤2 
(4) 
Adequate bone marrow, liver and renal function, with: 
• 
Calculated glomerular filtration rate (GFR): ≥45 mL/min  
• 
Albumin: >30 g/L 
• 
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase (AP): ≤5 times upper limit of normal (ULN)  
• 
Bilirubin: ≤3xULN (3×1.1 mg/dL) 
• 
Leukocytes: ≥3x109/L, and neutrophils: ≥1x109/L 
• 
Erythrocytes: ≥3.5x1012/L 
• 
Platelets: ≥90x109/L  
(5) 
Signed written informed consent prior to any study-related procedures. 
4.2 
Exclusion Criteria 
Subjects will be excluded for any of the following reasons: 
(1) 
Subject with resected primary tumour  
(2) 
Subjects with confirmed ductal carcinoma in situ 
(3) 
Men with breast cancer 
(4) 
Presence of an active infection at screening or history of a serious infection within the 
previous 6 weeks prior to the first 68Ga-OPS202 administration that might interfere with 
the PET and/or CT analysis 
(5) 
Subjects who have received any therapy for breast cancer 
(6) 
Prior or planned administration of a radiopharmaceutical within 8 half-lives of the 
radionuclide  
(7) 
Clinically relevant trauma within 2 weeks prior to first 68Ga-OPS202 administration  
(8) 
Any condition that precludes the proper performance of PET and/or CT scan: 
• 
Subjects who are not able to tolerate the CT contrast agent 
• 
Subjects with metal implants or arthroplasty, or any other objects that might 
interfere with the PET and/or CT analysis 
• 
Subjects unable to raise arms for prolonged imaging purposes  
• 
Subjects unable to lie still for the entire imaging time 
• 
Subjects weighing greater than 110 kg (243 lb) 
(9) 
Known hypersensitivity to radiolabelled NODAGA (1,4,7-triazacyclononane,1-glutaric 
acid 4,7 acetic acid), to Gallium-68, to somatostatin analogue peptide JR11 or to any of 
the excipients of 68Ga-OPS202 
(10) History of, or current active allergic or autoimmune disease, including asthma or any 
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(11) Known human immunodeficiency virus (HIV) or positive serology for HIV, hepatitis B 
or C 
(12) Administration of another investigational medicinal product within 30 days prior to first 
68Ga-OPS202 administration 
(13) Subjects who are pregnant, breast feeding or of childbearing potential not willing to 
practice effective contraceptive techniques during the study treatment period and for 
30 days after the last dose of 68Ga-OPS202 administration; pregnancy test must be 
performed at the start of the study and prior to 68Ga OPS202 administration 
(14) Subjects who have any severe and/or uncontrolled medical conditions or other conditions 
that could affect their participation in the study, including any mental condition rendering 
the subject unable to understand the nature, scope, and possible consequences of the 
study, and/or evidence of an uncooperative attitude 
(15) Subject who experienced a previous cancer (except basocellular carcinoma of the skin 
and/or in situ carcinoma of the cervix/uterus, and/or subjects treated with curative intent 
and free from disease for more than 5 years). 
4.3 
Rationale for Inclusion/Exclusion Criteria 
Eligibility criteria include those that define subjects with breast cancer eligible for imaging with 
68Ga-OPS202 PET/CT scan. There is no upper limit for age since eligibility criteria exclude 
conditions that could affect elderly participation in the study. 
4.4 
Subject Withdrawal Criteria and Procedures 
In accordance with the Declaration of Helsinki (and the applicable country’s acceptance), each 
subject is free to withdraw from the study at any time. The investigator also has the right to 
withdraw a subject from the study in the event of concurrent illness, AEs, pregnancy (see 
Section 8.1.4) or other reasons concerning the health or wellbeing of the subject, or in the case 
of lack of cooperation. In addition, a subject may be withdrawn from the study as described in 
Sections 3.7, 5.2.5, 6.2 and 8.1.6.  
If a subject decides to withdraw from the study after the administration of IIP, or the investigator 
decide to withdraw the subject, all efforts will be made to complete and report the observations 
up to the time of withdrawal as thoroughly as possible. A complete final evaluation at the time 
of the subject’s withdrawal should be made (see Sections 5.2.5) and an explanation given of 
why the subject is withdrawing or being withdrawn from the study. 
The reason for and date of withdrawal from the study must be recorded in the eCRF. If a subject 
withdraws consent, every attempt will be made to determine the reason. If the reason for 
withdrawal is an AE or a clinically significant laboratory test abnormality, monitoring will 
continue until the event has resolved or stabilised, the subject is referred to the care of a local 
health care professional, or a determination of a cause unrelated to the IIP or study procedure 
is made. The specific AE or test result(s) must be recorded in the eCRF. All evaluations should 
be performed, according to the protocol, on the day the subject receives IIP, or as soon as 
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5 
STUDY PROCEDURES 
5.1 
Study Schedule 
The schedule of procedures and assessments during the study is summarised in Table 3. 
Table 3 
Study Procedures and Assessments 
Study Visits [a] 
Screening 
Visit 1 
Day -14 to -1 
Visit 2[a] 
Day 1 
Visit 2[a] 
Day 2 
End of Study/Early 
Withdrawal Visit 3 
Day 14 (±3) 
Informed consent [b] 
X 
 
 
 
Eligibility criteria 
X 
X 
 
 
Demographics [c] 
X 
 
 
 
Medical history [d] 
X 
 
 
 
Prior therapies [d] 
X 
 
 
 
Concomitant therapies [e] 
X 
X 
X 
X 
Physical examination [f] 
X 
X 
 
X 
Vital signs [g] 
X 
X 
X 
X 
ECG [h] 
X 
 
 
X 
Haematology [i] 
X 
 
X 
X 
Blood chemistry [j] 
X 
 
X 
X 
Urinalysis [k] 
X 
 
X 
X 
Pregnancy test [l] 
ßHCG 
(blood test) 
Urinary HCG 
 
ßHCG 
(blood test) 
68Ga-OPS202 PET/CT 
imaging [m] 
 
X 
 
 
18F-FDG-PET scan [n] 
Any time during the study period 
Contrast enhanced CT [m] 
With 68Ga-OPS202 PET or 18F-FDG-PET 
Adverse events [o] 
X 
X 
X 
X 
Compliance [p] 
 
X 
 
 
Biopsy [q] 
X 
 
 
 
AE=adverse event, CT=computed tomography, ECG=electrocardiogram, 18F-FDG=18F-fluorodeoxyglucose, HCG=human 
chorionic gonadotropin, HER2= human epidermal growth factor receptor 2, ICL=imaging core laboratory, IIP=investigational 
imaging product, PET=positron emission tomography. 
(a) 
Study visits: Screening Visit up to 14 days before IIP administration; Subjects may be hospitalised overnight at the 
discretion of the investigator at Visit 2. All subjects (either hospitalised or not) will attend consultation on Day 2, 
which is part of Visit 2, for: review of AEs, new or changed concomitant medications, vital signs, haematology, 
biochemistry, urinalysis. 
(b) 
Informed consent: Must be obtained prior to undergoing any study specific procedures and will occur prior to the 
2-week screening period. 
(c) 
Demographics: Age, sex and self-reported race/ethnicity if authorised to be collected in the country. 
(d) 
Medical history and prior therapies: To include clinically significant diseases, surgeries, cancer history and all 
relevant medications. 
(e) 
Concomitant medications: Dose and indication will be recorded from 3 months prior to the IIP administration, at 
study entry and at each visit. Once the subject has withdrawn from/completed the study, concomitant medications and 
treatments should be recorded until all study treatment-related toxicities have resolved. 
(f) 
Physical examination: Major body systems, body weight, height (screening visit only).  
(g) 
Vital signs: pre-dose and at 0.5, 1, 2 and 4 hours post-injection (supine and standing systolic and diastolic blood 
pressure and heart rate, body temperature, respiratory rate). 
(h) 
ECG: Twelve-lead ECGs will be recorded at a paper speed of 25 mm/sec so that the different ECG intervals (RR, PR, 
QRS, QT) can be measured automatically as per study site usual practice. The ECG will be recorded with the subject 
in supine position after five minutes of rest until four regular consecutive complexes are available. 
(i) 
Haematology: Red blood cell (RBC) count, haemoglobin, haematocrit, mean corpuscular volume (MCV), mean 
corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cell (WBC) 
count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils) and platelet count. 
(j) 
Blood chemistry: urea, creatinine, creatinine clearance, chloride, bicarbonate, sodium, potassium, calcium, phosphate, 
total bilirubin, conjugated bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, 
gamma-glutamyl transferase, albumin, total protein, total cholesterol, triglycerides, fasting glucose. 


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(k) 
Urinalysis: Dipstick for pH, protein, ketones, bilirubin, blood, urobilinogen, nitrites, leukocyte esterase, glucose and 
specific gravity. 
(l) 
Pregnancy test: A pregnancy test will be performed at each visit particularly before 68Ga-OPS202 administration. 
(m) 
68Ga-OPS202 PET/CT imaging: PET acquisition at 0.5, 1 and 2 hours after 68Ga-OPS202 administration.  Iodinated 
i.v. CT contrast imaging (chest, abdomen, pelvis and brain). A single contrast enhanced computed tomography (ceCT) 
scan is required for the study. This can be acquired after either of the two PET scans (18F-FDG-PET or 68Ga-OPS202 
post the 2-hour acquisition). Low-dose CT scans will be acquired for the other PET scans when the ceCT is not 
obtained (see the Imaging Review Charter (IRC)). Anonymised and blinded to acquisition time images will be sent to 
the ICL. 
(n) 
18F-FDG-PET scan: 18F-FDG-PET scan, which is part of routine clinical diagnosis, will be performed during the 
study period and images sent to ICL. A ceCT or a low dose CT may be performed with the 18F-FDG-PET (see the 
IRC) 
(o) 
Adverse events: Subjects must be followed for AEs, regardless of relationship to IIP, from the time they signed the 
informed consent until 14±3 days after the dose of IIP. Clinically significant changes in physical examination, vital 
signs, electrocardiogram and laboratory findings will be recorded as an AE. The investigator will follow-up AEs until 
resolution or stabilisation. 
(p) 
Compliance: The peptide mass dose and the radioactivity dose injected will be recorded at Visit 2. 
(q) 
Biopsy: To be performed if not already done. Tumour biopsy, which is not a prerequisite for inclusion, is routinely 
performed for confirmation and staging of the disease, as well as classification according to hormone receptor status 
and HER2 status. For the study, an archived tumour sample (block is preferred over paraffin embedded slides) is 
required for the evaluation of sstr2 expression by immunohistochemistry staining.  
 
5.2 
Study Visits 
5.2.1 
Procedures for Screening and Enrolment (Visit 1) 
A signed and dated informed consent form will be obtained before screening procedures begin. 
Evaluations obtained as part of routine medical care and performed during the screening period 
may be used in place of the study-specific evaluations. Subjects will be asked to acknowledge 
and agree to the possible use of this information for the study by giving informed consent. 
After informed consent is obtained, subjects who are screened will be allocated a subject 
number. All screened subjects must be identifiable throughout the study. The investigator will 
maintain a list of subject numbers and names to enable records to be found at a later date if 
required. Subjects can be rescreened at a later date in the case of screening failure. 
The screening visit (Visit 1) will be performed within 14 days prior to the first 68Ga-OPS202 
administration. The following assessments will be performed: 
• 
Eligibility check (inclusion/exclusion criteria) 
• 
Demographic data (age, sex and self-reported race/ethnicity according to individual 
country regulations/requirements and if authorised in the country). The collection of 
these data is needed to establish whether or not there are potentially clinically important 
sex- and racial/ethnic-based differences in the anticipated effects of the studied product 
• 
Medical history (including clinically significant diseases, surgeries, cancer history) 
• 
Physical examination 
• 
Vital signs (body temperature, supine and standing systolic and diastolic blood pressure, 
heart rate, respiratory rate) 
• 
Body weight and height  
• 
ECG (recorded with the subject in supine position after five minutes of rest until four 
regular consecutive complexes are available) 
• 
Laboratory safety tests (blood sampling for haematology, biochemistry, and urinalysis) 


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• 
Beta human chorionic gonadotropin (ß-HCG) pregnancy test for women of childbearing 
potential 
• 
Prior and concomitant medications/therapies  
• 
Collection of AEs after signed informed consent has been obtained 
• 
Collection of historical paraffin embedded breast tumour blocks or slides with 
anatomical location of the lesion indicated 
• 
18F-FDG-PET scan (which can also be performed at any time during the study period, 
including the Screening period). 
Each investigator will also maintain a record of all subjects screened into the study (i.e. who 
signed the informed consent form). Records up to the time of study termination should be 
completed. In the event that the subject was not receiving IIP, the primary reason will be 
recorded. 
5.2.2 
Procedures Before Study IIP Administration (Day 1, Visit 2 Pre-dose) 
The following procedures will be performed on Day 1, prior to the IIP administration: 
• 
Eligibility check (inclusion/exclusion criteria) 
• 
Vital signs (body temperature, supine and standing blood pressure, heart rate and 
respiratory rate) 
• 
Physical examination (including body weight) 
• 
Pregnancy test (urine) 
• 
Concomitant therapies 
• 
Review of AEs. 
5.2.3 
Dosing (Day 1, Visit 2) 
The following procedures will be performed at Visit 2 Day 1:  
• 
One injection of 68Ga-OPS202 (Dosing) 
5.2.4 
Procedures after IIP Administration (Day 1 and Day 2, Visit 2 Post-dose) 
The following procedures will be performed at Visit 2 Day 1 post-dose:  
• 
Whole body PET imaging at 0.5, 1 and 2 hours after the injection of the IIP  
• 
A single ceCT scan will be performed according to the site standard procedure for chest, 
abdomen, pelvis and brain. This can be acquired after either of the two PET scans 
(18F-FDG-PET or 68Ga-OPS202 post the 2-hour acquisition). Low-dose CT scans will be 
acquired with PET scans when necessary for attenuation correction. See IRC for further 
details. 
• 
Review of AEs 
• 
New or changed concomitant medications 
• 
Vital signs at 0.5, 1, 2 and 4 hours post-injection (body temperature, supine and standing 
blood pressure, heart rate and respiratory rate). 
 
Subjects may be hospitalised overnight at the discretion of the investigator. All subjects (either 
hospitalised or not) will attend consultation on Day 2, which is part of Visit 2.  


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On Day 2, the investigator will evaluate if the subject is fit to be discharged home. Subjects 
who are not hospitalised will return to the investigator site on Day 2. 
The following procedures will be performed at Visit 2 Day 2:  
• 
Review of AEs 
• 
New or changed concomitant medications 
• 
Vital signs (body temperature, supine and standing blood pressure, heart rate and 
respiratory rate) 
• 
Clinical laboratory tests (blood sampling for haematology and biochemistry, and 
urinalysis) 
Upon discharge from the hospital on Visit 2 (Day 2), the subject will be asked to return to the 
study site on Day 14 (±3 days) for safety follow-up (Visit 3). 
5.2.5 
End of Study Visit or Early Withdrawal Visit (Day 14±3, Visit 3) 
The subject’s participation in the study will be considered to have ended at the time of the last 
visit (Visit 3, at Day 14±3 days). 
For subjects who complete the study, final evaluations will be performed on Day 14 (±3 days) 
after the subject receives the IIP. Subjects with ongoing AEs or clinically significant laboratory 
test abnormalities (as determined by the investigator) will be monitored as described in Section 
8.1.3 and Section 8.1.2, respectively. 
The following procedures will be performed at the End of Study (Visit 3, Day 14±3 days) or 
Early Withdrawal visit: 
• 
Review of AEs 
• 
New or changed concomitant therapies 
• 
Physical examination including body weight 
• 
Vital signs (body temperature, supine and standing blood pressure, heart rate and 
respiratory rate) 
• 
ECG (recorded with the subject in supine position after five minutes of rest until four 
regular consecutive complexes are available) 
• 
Clinical laboratory tests (blood sampling for haematology and biochemistry, and 
urinalysis) 
• 
Pregnancy test (ßHCG blood test). 
6 
INVESTIGATIONAL IMAGING PRODUCT AND DOSING OF SUBJECTS 
6.1 
Investigational Imaging Product Preparation and Radiolabelling Kit, Storage 
and Accountability 
6.1.1 
Investigational Imaging Product and Radiolabelling Kit Storage and Security 
The investigator, or an approved representative (e.g. pharmacist), will ensure that all 
radiolabelling kit, IIP and any other study related material are stored in a secured area, under 
recommended temperature monitored storage conditions, in accordance with applicable 
regulatory requirements. 
6.1.1.1 
Spillage 
All due precautions and site procedures should be implemented to prevent spillage or leakage 
of radiodiagnostics. Syringes, intravenous lines, venous access should all be secured and the 


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connections thoroughly checked. The injection/infusion line should be taped in a loop and taped 
to the subject to prevent direct tension between the line and the venous access. 
Despite precautions, if spillage or leakage should occur, then the site procedures must be 
implemented to protect the subject, staff and members of the public from radiation exposure. 
The subject should be moved from the area of the spillage or leakage while the area is 
decontaminated. Details of the spillage or leakage should be recorded (including how the 
incident happened, the time of the incident, an estimate (if possible) of the amount of substance 
lost) and the measures taken. In addition, the incident is to be reported in the same manner as 
an adverse event using the MedDRA PT Product Leakage and as appropriate PT Occupational 
exposure to radiation (if there is exposure to staff) and PT Exposure to radiation (if there is 
exposure to the subject or members of the public). 
6.1.2 
Investigational Imaging Product Preparation 
The investigator, or an approved representative (e.g. pharmacist), will ensure that all IIP are 
reconstituted, radiolabelled and dispensed by qualified staff members. 
6.1.3 
Investigational Imaging Product and Radiolabelling Kit Accountability 
All radiolabelling kits, IIP and any other study related material are to be accounted for on the 
IIP accountability log provided by the sponsor. It is essential that all used and unused supplies 
are retained for verification (by the sponsor or sponsor’s representative). The investigator 
should ensure adequate records are maintained in the accountability log. 
The destruction of used and unused radiolabelling kit and IIP should be carried out only after 
any discrepancies have been investigated and satisfactorily explained and the reconciliation has 
been accepted. The study radiolabelling kits, IIP and any other study related material will be 
destroyed on site. 
6.1.4 
Investigational Imaging Product (68Ga-OPS202) 
68Ga-OPS202 is an imaging radiopharmaceutical with three main components, namely: 
• 
JR11, an antagonist somatostatin analogue that binds to sstr2 receptors 
• 
NODAGA, a chemical chelator moiety and 
• 
68Ga, a positron-emitting radionuclide with a half-life of 68 minutes.  
The IIP is a solution for injection prepared prior to administration from a radiolabelling "cold" 
kit and a 68Ge/68Ga-generator. The OPS202 peptide is provided in a sterile two-vial 
radiolabelling kit constituted of:  
• 
freeze-dried lyophilised powder containing 50 μg non-radiolabelled precursor OPS202 
and excipients (Vial A)  
• 
and the solvent for reconstitution (Vial B) to be used prior to radiolabelling. 
The final radiolabelled IIP (68Ga-OPS202) (one kit per subject dose) will be prepared, up to 
3 hours prior to administration, in the local radiopharmacy, in a two-step aseptic compounding 
process, according to Good Radiopharmaceutical Practice (GRPP) per EANM guidelines and 
according to national regulations on radiopharmaceuticals preparation: 
• 
Reconstitution prior to radiolabelling of Vial A and Vial B, 
• 
Radiolabelling of the precursor OPS202 achieved by the addition of a 6-mL sterile 
hydrochloric acid solution of 68Ga, eluted from a sterile pharmaceutical grade 68Ge/68Ga 
generator. 


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68Ga-radiolabelling yields the IIP 68Ga-OPS202 as a solution for injection. After QC sampling, 
QC testing and release, the volume to be administered to the subject is withdrawn from the IIP 
vial, containing up to 45 μg OPS202. This volume is determined to obtain the target 
radioactivity dose at the time of administration, taking into account the decay of 68Ga. All 
subjects will receive a single dose of 150-200 MBq 68Ga-OPS202 (IIP), as a slow i.v. bolus 
injected over 1 minute. 
The radioactivity in the syringe is measured before and after the injection of 68Ga-OPS202 to 
the subject; the decay-corrected difference between these two measurements (in MBq) 
corresponds to the radioactivity dose injected to subject. In addition, any extravasation during 
infusion should be measured and this radioactivity deducted from the calculated amount 
injected into the subject. 
There are no fasting conditions, nor food restrictions that should apply when administering 
68Ga-OPS202 to the subject.  
6.2 
Study Drugs Administered 
68Ga-OPS202 is prepared, up to 3 hours prior to administration, by 68Ga-radiolabelling of an 
OPS202 radiolabelling kit containing 50 μg of peptide.  
6.3 
Concomitant Medication/Therapy 
Any relevant prior or concomitant therapy or medication given to a subject within 3 months 
before IIP administration, during IIP administration and up to the end of the follow-up period 
will be indicated in the eCRF. Dose and generic name or tradename will be recorded. 
The following concomitant medications /therapies are not permitted during this study up to 
48 hours post PET/CT scan: 
• 
Administration of any radiopharmaceutical 
• 
On Visit 2 parenteral amino acid solutions and any formulation of diuretics are not 
allowed. Stable adjusted diuretics such as for subjects with hypertension are permitted. 
Long acting SSAs, ie, Somatuline® Autogel® /Depot® (60, 90 or 120 mg) and Sandostatin® 
LAR (20 or 30 mg) will not be allowed within 28 days prior to the 68Ga-OPS202 PET/CT exam 
(at Visit 2). Short acting Sandostatin® is allowed during the study with a washout period of 
24 hours before the 68Ga-OPS202 PET/CT (Visit 2), to avoid possible interaction between the 
non-radioactive SSA and OPS202.  
Other concomitant medications are permitted during this study at the discretion of the 
investigator; however, they must be monitored closely and every effort should be made to keep 
their dose and dose regimen constant throughout the course of the study.  
6.4 
Procedures for Monitoring Subject Compliance 
The IIP is administered via the i.v. route by the investigator or his/her delegate. Therefore, no 
specific procedure is required for monitoring subject compliance. The injected peptide mass 
dose (calculated from the IIP volume) and radioactivity dose will be recorded in the medical 
file and in the eCRF for each subject. 
The investigator will ensure that the subject did not take and is not taking any of the prohibited 
medication listed in Section 6.2 during the study period. 


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7 
ASSESSMENT OF EFFICACY 
For the primary, secondary and exploratory endpoints all the sets of images obtained at Visit 2 
and one 18F-FDG-PET and one ceCT scan will be sent to an ICL for quality control and 
management of the reads. The centralised reads will be undertaken by two independent 
experienced radiologists and/or nuclear medicine physicians, and a third for adjudication of 
discordances for most of the reads. The readers will be specifically trained for this protocol. 
Full details of the read design and conduct will be provided in the IRC. 
For the primary endpoint analysis, the number of lesions and quality of the images will be taken 
into consideration by the readers. Scans will be blinded to subject identification, site and timing 
post injection. No adjudication will be conducted as inter-reader differences will be part of the 
evaluation. 
The sequence of image display and recording of results will be as follows on a per subject basis: 
(1) 
Review of the three image sets of   68Ga-OPS202 scans in randomised fashion, with CT 
image fusion. The ceCT images acquired will be used for co-registration. Two readers 
will read and a third will adjudicate any differences. 
(2) 
18F-FDG-PET images for standard-of-truth assessments will be reviewed by two 
radiologists not involved in 68Ga-OPS202 PET/CT images read, and the lesions mapped 
to the 68Ga-OPS202 read. Two readers will read and a third will adjudicate any 
differences. 
(3) 
SUVmax and SUVmean calculations of the five most avid lesions per organ on 
68Ga-OPS202 PET scans (primary breast lesion, liver, lymph nodes, bone, lungs and 
brain) will be conducted by the ICL after identification of the lesions by one of the 
primary readers. 
(4) 
Review of the lesion-to-background ratios in each major anatomical site (primary breast 
lesion, liver, lymph nodes, bone, lungs and brain) based on the evaluation of up to five 
most avid lesions per organ will be managed by the ICL after the lesions have been 
identified by one of the primary readers. 
(5) 
For image quality, direct comparison of the three 68Ga-OPS202 scans acquired at 
different times, will be conducted for the primary breast cancer and then for all other 
lesions as the final step of the blinded read. The readers will be allowed to select whether 
one, two or all three acquisitions are optimal. The readers will be blinded to time point 
sequence. No adjudication will be required. 
(6) 
The 68Ga-OPS202 PET scans will be compared with the 18F-FDG-PET scan (with ceCT).   
 
(a) 
Primary Efficacy Endpoint and Evaluation 
The co-primary endpoint is therefore calculated in the following way: 
(1) 
The number of subjects with newly diagnosed breast cancer with primary sstr2 positive 
lesions identified by 68Ga-OPS202 at any timepoint, divided by the total number of 
subjects imaged to obtain the prevalence in this study population. 
(2) 
The identification of the optimum acquisition time(s) based on differences in the number 
of lesions identified at each scan, and the reader interpretation of the optimum image in 
the primary breast lesions.  The optimum image acquisition time could be one, two or all 
three acquisitions timepoints i.e. no noticeable difference between 0.5, 1 and 2 hours post 
infusion.   


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(b) 
Secondary Efficacy Endpoints and Evaluations 
Key Secondary Endpoint: 
• 
Differences in the number of lesions detected by 68Ga-OPS202 between the three PET 
acquisition timepoints (0.5, 1 and 2 hours), and reader interpretation of optimal image(s) 
in nodular and metastatic lesions.  Significant uptake of 68Ga-OPS202 for the evaluation 
of a lesion is an avid lesion defined by the blinded readers at one of the acquisition 
timepoints as an easily identifiable lesion radiologically, where there has been clear focal 
uptake of 68Ga-OPS202 and 1.5-fold or greater uptake than in the non-tumoural liver and 
lung parenchyma. 
• 
The SUVmean and SUVmax in the primary lesion between each of the three timepoints, 
measured in the most avid lesions (using the 68Ga-OPS202 scans).  This is assessed by 
the tumour-to-background ratio in the primary tumour and each of the major anatomic 
sites (liver, lymph nodes, bone, lungs and brain); the background consists of 
non-tumoural liver parenchyma or aortic blood where sufficient liver is not available. 
Identification of lesions to be used will be made by one of the two primary readers.  
Other Secondary Endpoints: 
• 
Comparison to standard-of-truth for the primary breast tumour: 
- 
(68Ga-OPS202 PET/CT) / (18F-FDG-PET/CT) 
- 
For each acquisition time of 68Ga-OPS202 PET.   
This will be repeated for each of the other anatomical locations: 
- 
Lymph nodes  
- 
Liver  
- 
Axial/appendicular skeleton  
- 
Lungs 
- 
Brain 
The second component of the co-primary and appropriate secondary endpoints will also be 
evaluated on a radioactivity dose MBq/kg of body weight to evaluate if the subject mass has an 
effect on the diagnostic accuracy. 
Exploratory Endpoints: 
• 
Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging sstr2 positive breast cancer 
tumours by both subject-based and lesion-based analysis compared to standard-of-truth 
• 
SNR calculated from: SUVmean/SUVSD at the three PET acquisition timepoints using the 
same lesions as for SUVmax.  The background will be the same background as for 
SUVmax, of either lesion-free volume of interest (VOI) in the liver or aorta, if insufficient 
lesion free liver is available 
• 
Estimated correlation in terms of number of avid lesions between 68Ga-OPS202 PET at 
the agreed “optimum timepoint” and 18F-FDG PET scan.  This will be based on lesion 
counts off the identified optimal timepoint or from the 1-hour timepoint if no optimum 
is identified 
• 
Estimated correlation between tumour uptake and results of immunohistochemistry 
staining of sstr2 of the primary tumour. 
For further details on efficacy secondary endpoints assessment, refer to the IRC. 
 


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(c) 
Methods and Timing of Assessing, Recording, and Analysing Efficacy Data 
Methods for assessing efficacy data are listed below and are described in further detail in the 
IRC. Timing of efficacy acquisitions are discussed in Section 5. The efficacy data are obtained 
from the ICL and will be obtained using electronic means.  The methods of analyses are 
discussed in Section 11.4.4. 
All images will be sent to a central ICL for QC and central read management.  This comprises 
the following images: 
• 
All 68Ga-OPS202 PET/CT scans 
• 
One 18F-FDG-PET/CT scan. 
• 
One ceCT scan. 
 
The details of the imaging management and read design will be fully described in the IRC.  This 
will include the following: 
• 
Full acquisition guidelines for the site, for IIP and ceCT scan 
• 
Process for PET scanner quality control (phantom assessments and reporting) 
• 
Image transmission methodology 
• 
Core lab QC methodology and management of the images 
• 
Read design for primary endpoint  
• 
Read design for secondary endpoint and process for calculating tumour-to-background 
ratio and SUVmean and SUVmax 
• 
Design of exploratory endpoints 
• 
Conduct of the read 
• 
Management, training and inter-reader evaluation 
• 
Data management 
• 
Data export overview 
• 
Archiving of images. 
7.1 
Eligible and Evaluable Subjects 
• 
All subjects who receive 68Ga-OPS202 are “eligible” subjects and will be included in the 
safety analysis. 
• 
All eligible subjects with one or more readable 68Ga-OPS202 PET and a readable ceCT 
scan will be included in the first component of the co-primary endpoint analysis to 
determine sstr2 positive prevalence. 
• 
The following describes those subjects that are eligible and “evaluable” for the second 
component of the co-primary endpoint to assess the optimum timing of the PET scan 
following infusion of 68GaOPS202: 
- 
A readable ceCT scan 
- 
At least two 68Ga-OPS202 PET scans that are readable (three images are to be 
acquired but 2 of these, MUST be readable by the central readers; if only two PET 
scans are acquired BOTH must be readable) with at least one avid lesion identified 
by central readers.   
 


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8 
ASSESSMENT OF SAFETY 
The safety and tolerability of 68Ga-OPS202 consists of evaluating: 
• 
AEs throughout the study 
• 
Clinical laboratory test results (serum chemistry, haematology, urinalysis) throughout 
the study 
• 
Vital signs measurements (blood pressure and heart rate) throughout the study  
• 
ECG at Visit 1 (Screening) and Visit 3 (End of treatment/Early Withdrawal) 
• 
Physical examination results throughout the study 
• 
Concomitant medication usage throughout the study. 
8.1 
Adverse Events 
Adverse events will be monitored from the time that the subject gives informed consent and 
throughout the study (see Section 3.6 for a definition of the study duration) and will be elicited 
by direct, nonleading questioning or by spontaneous reports. Further details for AE reporting 
can be found in Section 8.1.1. 
Definition of an Adverse Event 
An AE is the development of an undesirable medical condition or the deterioration of a 
pre-existing medical condition following or during exposure to a pharmaceutical product, 
whether or not considered causally related to the product. An undesirable medical condition can 
be symptoms (e.g. nausea, chest pain), signs (e.g. tachycardia, enlarged liver) or the abnormal 
results of an investigation (e.g. laboratory findings, electrocardiogram). In clinical studies, an 
AE can include an undesirable medical condition occurring at any time, including run in or 
washout periods, even if no IIP has been administered.  
This definition includes events occurring from the time of the subject giving informed consent 
until the end of the study (as defined in Section 3.6). 
8.1.1 
Categorisation of Adverse Events 
8.1.1.1 
Intensity Classification 
Adverse events will be recorded and graded according to the current version of the NCI-CTCAE 
(version 5.0). In view of meta-analyses, and for conversion purposes, the following conversion 
mapping will apply if the NCI-CTCAE scale is not available for a given AE: 
• 
NCI-CTCAE Grade 1 corresponds to mild 
• 
NCI-CTCAE Grade 2 corresponds to moderate 
• 
NCI-CTCAE Grade 3 corresponds to severe 
• 
NCI-CTCAE Grade 4 corresponds to life threatening/disabling 
• 
NCI-CTCAE Grade 5 corresponds to death (related to AE). 
Where:  
• 
Mild: symptoms do not alter the subject’s normal functioning 
• 
Moderate: symptoms produce some degree of impairment to function, but are not 
hazardous, uncomfortable or embarrassing to the subject 
• 
Severe: symptoms definitely hazardous to wellbeing, significant impairment of function 
or incapacitation 


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• 
Life threatening: any event that places the subject at immediate risk of death from the 
event as it occurred, i.e. it does not include a reaction that, had it occurred in a more 
severe form, might have caused death (also see Section 8.1.3). 
8.1.1.2 
Causality Classification 
The relationship of an AE to IIP administration will be classified according to the following: 
• 
Related: reports including good reasons and sufficient information (e.g. plausible 
temporal 
relationship, 
dose 
response 
relationship, 
biological/pharmacological 
plausibility, positive dechallenge and/or rechallenge) to assume a causal relationship 
with IIP administration in the sense that it is plausible, conceivable or likely 
• 
Not related: reports including good reasons and sufficient information (e.g. implausible 
time sequence and/or attributable to concurrent disease or other drugs) to rule out a causal 
relationship with IIP administration. 
8.1.1.3 
Assessment of Expectedness 
The expectedness of an AE shall be determined by the sponsor according to the IIP IB.  
The reference document for assessing expectedness of AEs/event in this study will be the 
current IB. 
8.1.1.4 
Laboratory Test Abnormalities 
All abnormalities in laboratory test values should only be reported as AEs if any of the 
following apply:  
• 
They require intervention or a diagnosis evaluation to assess the risk to the subject, 
• 
They are considered as clinically significant by the investigator, or the laboratory test 
abnormality suggests a disease and/or organ toxicity that is new or has worsened from 
baseline based on sponsor review. 
8.1.1.5 
Abnormal Physical Examination Findings  
Clinically significant changes, in the judgement of the investigator, in physical examination 
findings (abnormalities) will be recorded as AEs.  
8.1.1.6 
Other Investigation Abnormal Findings 
Abnormal test findings as judged by the investigator as clinically significant 
(e.g. electrocardiogram changes) or require intervention or diagnostic evaluation to assess the 
risk to the subject, should be recorded as AEs.  
8.1.2 
Recording and Follow up of Adverse Events 
At each visit, the subject should be asked a non-leading question such as: “How have you felt 
since the administration or last administration of the study compound?” 
All observed or volunteered AEs, regardless of study arm or suspected causal relationship to 
IIP, will be recorded on the AE page(s) of the eCRF. Events involving drug reactions, accidents, 
illnesses with onset during the treatment phase of the study, or exacerbations of pre-existing 
illnesses should be recorded according to NCI terminology. 
Any AEs already recorded and designated as ‘continuing’ should be reviewed at each 
subsequent assessment. 
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as an SAE 
requiring immediate notification to the sponsor or its designated representative. For all AEs, 


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sufficient information should be obtained by the investigator to determine the causality of the 
AE (i.e. IIP or other illness). The investigator is required to assess causality and record that 
assessment in the eCRF. Follow-up of the AE, after the date of IIP discontinuation, is required 
if the AE or its sequelae persist. Follow-up is required until the event or its sequelae resolve or 
stabilise at a level acceptable to the investigator and the sponsor’s clinical monitor or his/her 
designated representative. 
8.1.3 
Reporting of Serious Adverse Events 
All SAEs (as defined below) regardless of study arm or suspected relationship to IIP must be 
reported immediately (within 24 hours of the investigator’s knowledge of the event) using the 
pharmacovigilance contact email: 
specified at the beginning of this 
protocol. If the immediate report is submitted by telephone, this must be followed by detailed 
written reports using the SAE report form. 
An SAE is any AE that: 
(1) 
Results in death, 
(2) 
Is life threatening, that is any event that places the subject at immediate risk of death 
from the event as it occurred. It does not include an event that, had it occurred in a more 
severe form, might have caused death, 
(3) 
Results in inpatient hospitalisation or prolongation of existing hospitalisation, excluding 
admission for social or administrative reasons (see further), 
(4) 
Results in a persistent or significant disability/incapacity, where disability is a substantial 
disruption of a person's ability to conduct normal life functions, 
(5) 
Results in congenital anomaly/birth defect in the offspring of a subject who received the 
IIP, 
(6) 
Is an important medical event that may not result in death, be life threatening, or require 
hospitalisation when, based upon appropriate medical judgement, may jeopardise the 
subject and may require medical or surgical intervention to prevent one of the outcomes 
listed in this definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalisation, or the development of drug 
dependency or drug abuse. 
In addition to the above criteria, any additional AE that the sponsor or an investigator considers 
serious should be immediately reported to the sponsor and included in the corporate SAEs 
database system. 
• 
Hospitalisation is defined as any inpatient admission (even if less than 24 hours). For 
chronic or long-term inpatients, inpatient admission also includes transfer within the 
hospital to an acute/intensive care inpatient unit. 
• 
Prolongation of hospitalisation is defined as any extension of an inpatient 
hospitalisation beyond the stay anticipated/required in relation to the original reason for 
the initial admission, as determined by the investigator or treating physician. For 
protocol-specified hospitalisation in clinical studies, prolongation is defined as any 
extension beyond the length of stay described in the protocol. Prolongation in the absence 
of a precipitating, treatment-emergent, clinical AE (i.e. not associated with the 
development of a new AE or worsening of a pre-existing condition) may meet criteria 
for "seriousness" but is not an adverse experience and thus is not subject to immediate 
reporting to the sponsor.  
PPD


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• 
Pre-planned or elective treatments/surgical procedures should be noted in the subject’s 
screening documentation. Hospitalisation for a pre-planned or elective treatment/surgical 
procedure should not be reported as an SAE unless there are complications or sequelae 
that meet the criteria for seriousness described above. 
Any SAE must be reported immediately (within 24 hours), to Ipsen Pharmacovigilance email 
(preferably) or fax number specified at the beginning of this protocol, independent of the 
circumstances or suspected cause, if it occurs or comes to the attention of the investigator at 
any time during the study period. 
Any AE/SAE with a suspected causal relationship to IIP administration occurring at any other 
time after completion of the study must be promptly reported. 
The following information is the minimum that must be provided to the sponsor within 24 hours 
for each SAE: 
• 
Study number 
• 
Centre number 
• 
Subject number 
• 
AE 
• 
Investigator's name and contact details 
The additional information included in the SAE form must be provided to the sponsor or 
representative as soon as it is available. The investigator should always provide an assessment 
of causality for each event reported to the sponsor. Upon receipt of the initial report, the sponsor 
will ask for the investigator's causality assessment if it was not provided with the initial report. 
The investigator should report a diagnosis or a syndrome rather than individual signs or 
symptoms. The investigator should also try to separate a primary AE considered as the foremost 
untoward medical occurrence from secondary AEs which occurred as complications. 
8.1.4 
Pregnancy 
Pregnancy itself is not regarded as an AE unless there is a suspicion that the IIP has interfered 
with a contraceptive method. If pregnancy occurs during the study, the outcome of the 
pregnancy will then need to be collected after the study and it may be necessary to discontinue 
administration of the IIP.  
Information regarding pregnancies must be collected on the AE page of the eCRF and reported 
to the sponsor as an SAE. The sponsor will request further information from the investigator as 
to the course and outcome of the pregnancy using the Sponsor’s Standard Pregnancy Outcome 
Report Form.  
The investigator must instruct all subjects to inform them immediately should they become 
pregnant during the study. In case the investigator becomes aware of pregnancy occurring in a 
subject (pregnancy test before exposure to the IIP), the IIP should not be administered and the 
subject followed up until Visit 3 (End of the study). The investigator should counsel the subject, 
discuss the risks, if any, and the possible effects on the foetus. Monitoring of the subject who 
becomes pregnant during the study after the administration of the single IIP injection should 
continue until conclusion of the pregnancy, which may involve follow up after the subject’s 
involvement in the study has ended (as per Ipsen’s standard pharmacovigilance). 
Pregnancies with a probable conception date within completion of the study (30 days after 
subject’s last dose of IIP) must also be reported to the investigator for onward reporting to the 
sponsor. 


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8.1.5 
Deaths 
For AEs leading to death, NCI CTCAE Grade 5 is the only appropriate grade (see 
Section 8.1.1.1). Deaths that cannot be attributed to an NCI CTCAE term associated with Grade 
5 or that cannot be reported within an NCI CTCAE category as ‘Other’ have to be reported as 
one of these four AE options: 
• 
Death not otherwise specified (NOS) 
• 
Disease progression NOS 
• 
Multi-organ failure 
• 
Sudden death. 
The term “sudden death” should only be used for the occurrence of an abrupt and unexpected 
death due to presumed cardiac causes in a patient with or without pre-existing heart disease, 
within 1 hour of the onset of acute symptoms or, in the case of an unwitnessed death, within 
24 hours after the patient was last seen alive and stable. If the cause of death is unknown and 
cannot be ascertained at the time of reporting, “unexplained death” should be recorded on the 
Adverse Event eCRF. If the cause of death later becomes available (e.g. after autopsy), 
“unexplained death” should be replaced by the established cause of death.” 
8.1.6 
Discontinuation/Withdrawal due to Adverse Events/Serious Adverse Events 
Discontinuation/withdrawal 
due 
to 
AEs 
should 
be 
distinguished 
from 
discontinuation/withdrawal due to insufficient response to the IIP (see Section 4.3). 
In all cases, the investigator must ensure the subject is adequately followed up (see 
Section 8.1.2). 
Reporting to Competent Authorities/IECs/IRBs/Other Investigators 
The sponsor will ensure that processes are in place for submission of reports of SUSARs 
occurring during the study to the CA, independent ethics committees (IECs) and other 
investigators concerned by the IIP. Reporting will be done in accordance with the applicable 
regulatory requirements. 
8.2 
Clinical Laboratory Tests 
Blood samples will be collected at all study visits (Screening Visit [Visit 1], Day 2 [Visit 2], 
and End of Study/Early Withdrawal [Visit 3]) (see schedule of assessment in Table 3) for the 
evaluation of haematology and serum chemistry.  
The investigator will review the safety laboratory test results, document the review, and record 
any clinically relevant result occurring or observed during the study in the AE section of the 
eCRF (see Section 8.1.1.4 for abnormal laboratory tests that should be recorded as AEs). 
All clinically relevant abnormal laboratory tests occurring during the study will be repeated at 
appropriate intervals until they return to Baseline or to a level deemed acceptable by the 
investigator and the sponsor’s clinical monitor (or his/her designated representative) or until the 
abnormality is explained by an appropriate diagnosis.  
8.2.1 
Haematology 
Blood samples will be collected (in a potassium ethylenediaminetetraacetic acid [EDTA] tube) 
to assess the following parameters: red blood cell (RBC) count, haemoglobin, haematocrit, 
mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular 
haemoglobin concentration (MCHC), white blood cell (WBC) absolute count (neutrophils, 
lymphocytes, monocytes, eosinophils, basophils) and platelet count. 


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8.2.2 
Blood Biochemistry 
Blood samples will be collected at all visits to assess the following parameters: 
• 
urea, creatinine, creatinine clearance, total bilirubin, conjugated bilirubin 
• 
chloride, bicarbonate, sodium, potassium, calcium, phosphate 
• 
AP, AST, ALT, GGT 
• 
albumin, total protein, total cholesterol, triglycerides, fasting glucose. 
8.2.3 
Urinalysis 
Fresh urine samples (at least 10 mL) will be collected at all visits to assess the following 
parameters: pH, protein, ketones, bilirubin, blood, urobilinogen, nitrites, leukocyte esterase, 
glucose and specific gravity by dipstick.  
Microscopy will be performed, if indicated, but results will not be collected in the eCRF. If in 
the opinion of the investigator there are any clinically significant abnormalities in microscopy, 
they will be recorded as an AE in the eCRF. 
8.2.4 
Pregnancy Test 
A ßHCG test will be performed for all female subjects of childbearing potential at Screening 
(Visit 1) and End of Study Visit (Visit 3). A urinary hCG test will be performed at Visit 2 before 
first IIP administration and if clinically indicated. Any subject becoming pregnant during the 
study will be withdrawn. All pregnancies that occur during the study are to be reported as 
described in Section 8.1.4. 
8.2.5 
Putative Antibody Testing 
No putative antibody testing is planned. 
8.2.6 
Other Clinical Laboratory Tests 
No other clinical laboratory tests are planned. 
8.3 
Physical Examination 
Physical examinations, including body weight, will be conducted at Screening (Visit 1), IIP 
administration visit (Visit 2 only on Day 1) and End of Study (Visit 3)/Early Withdrawal (see 
Table 3), and height will be measured at Screening.  
Any clinically significant physical examination findings (abnormalities) observed during the 
study will be reported as AEs. Any physical examination findings (abnormalities) persisting at 
the end of the study will be followed by the investigator until resolution or until reaching a 
clinically stable endpoint. 
8.4 
Vital Signs 
Blood pressure and heart rate will be assessed at Screening (Visit 1), IIP administration visit 
(Visit 2: Day 1 pre-dose and at 0.5, 1, 2, 4 hours post-injection and on Day 2), and End of Study 
(Visit 3)/Early Withdrawal (see Table 3), with an automated device so that measurements are 
independent of the observer. Blood pressure and heart rate will be recorded after five minutes 
rest in sitting position and after one minute standing. Absolute values and change from Baseline 
will be analysed. 
Respiratory rate and temperature (tympanic/oral) will be recorded at the same timepoints. 
8.5 
Electrocardiography 
An ECG analysis will be included as a safety evaluation/endpoint in this study. 


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The ECGs will be recorded at Screening Visit (Visit 1), and End of Study/Early Withdrawal 
(Visit 3). 
Twelve-lead ECGs will be recorded at a paper speed of 25 mm/sec so that the different ECG 
intervals (RR, PR, QRS, QT) can be measured automatically as per study site usual practice. 
The ECG will be recorded with the subject in supine position after five minutes of rest until 
four regular consecutive complexes are available. ECG interval estimates will be measured as 
per study site usual practice, in this study. 
Any clinically significant abnormalities will be recorded as AEs. 
 


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9 
ASSESSMENTS OF PHARMACOKINETICS/PHARMACODYNAMICS 
Pharmacokinetics and pharmacodynamics are not assessed in this study. 
10 
EXPLORATORY BIOMARKERS AND BIOBANKING 
No exploratory biomarker collection or biobanking are included in this protocol. 


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11 
STATISTICS 
11.1 
Analyses Populations 
The following population will be used during statistical analyses: 
• 
Eligibility screened population: All subjects screened (i.e. who signed the informed 
consent).  
• 
Safety population: All subjects who received the dose of study IIP. 
• 
68Ga-OPS202 screened population: All subjects who received the dose of study IIP and 
for whom PET/CT scan images are readable for at least one timepoint. This population 
encompasses both subjects with sstr2 positive lesion(s) and those with sstr2 negative 
lesions (no avid lesion with 68Ga-OPS202).   
• 
Sstr2 positive population: All subjects who received the dose of study IIP and for whom 
68Ga-OPS202 PET/CT scan images are readable for at least one timepoint and have one 
avid lesion identified by central readers, 18F-FDG-PET/CT scan and a ceCT scan 
confirmed by the central readers. 
• 
Sstr2 positive evaluable population: 68Ga-OPS202 sstr2 positive population with at 
least two evaluable 68Ga-OPS202 timepoints, 18F-FDG-PET/CT scan and a ceCT scan 
confirmed by the central readers. 
11.1.1 
Populations Analysed 
The co-primary analysis based on the primary efficacy endpoint to determine sstr2 positive 
percentage will use the 68Ga-OPS202 screened population as the denominator. The co-primary 
analysis based on the primary efficacy endpoint to assess optimum imaging timing of the PET 
scan following 68Ga-OPS202 injection will be performed on the sstr2 positive evaluable 
population. In addition, secondary/confirmatory analysis may be performed on the sstr2 
positive population. 
The analyses of safety data will be performed based on the safety population. 
11.1.2 
Subject Allocation and Reasons for Exclusion from the Analyses 
The reasons for subject exclusions from each of the populations will be listed and tabulated. 
11.2 
Sample Size Determination 
It is anticipated that a total of approximately 54 subjects will be enrolled in the study for 
68Ga-OPS202 PET/CT imaging, to obtain around 16 sstr2 positive BC evaluable subjects. 
Considering the estimated prevalence of sstr2 overexpression in breast cancer, the overall 
number of subjects to be administered 68Ga-OPS202 in the study will be over 50. However, 
when the ICL identifies 16 sstr2 positive evaluable subjects, with a minimum of two subjects 
with advanced disease, the study will be complete. 
This estimation of 16 sstr2 positive BC evaluable subjects is considered appropriate for a 
descriptive analysis and it is not based on a formal statistical sample size calculation. In the 
event that a subject misses an imaging exam and/or measurement relevant to the primary and 
key secondary endpoints, an additional subject will be recruited as a replacement to ensure an 
adequate sample size in the sstr2 positive BC evaluable set.  
11.3 
Significance Testing and Estimations 
The analysis will be descriptive and no formal statistical tests are planned for the primary and 
secondary endpoints. 


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11.4 
Statistical/Analytical Methods 
Statistical analyses will be performed by an external Contract Research Organisation (CRO), 
managed by the sponsor’s Biometry Department. 
A Statistical Analysis Plan (SAP) describing the planned statistical analysis in detail with tables, 
figures and listings templates will be developed as a separate document. The SAP will be 
prepared before the first subject first visit. 
Statistical evaluation will be performed using Statistical Analysis System (SAS)® (version 9.2 
or higher). 
11.4.1 
Demographic and Other Baseline Characteristics 
Descriptive summary statistics (n, mean, standard deviation (SD), median, minimum, 
maximum) and frequency counts of demographic and baseline data (medical history, 
concomitant disease, predosing AEs and ongoing medical history, prior medications and 
therapies, baseline symptoms, etc.) will be presented for the safety, sstr2 positive evaluable and 
sstr2 positive populations. 
11.4.2 
Homogeneity of Treatment Groups 
Not applicable. 
11.4.3 
Subject Disposition and Withdrawals 
The numbers and percentages of subjects screened, enrolled and included in each of the sstr2 
positive evaluable, sstr2 positive and safety populations will be tabulated. The reasons for 
subject exclusions from each of the populations will be listed and tabulated. In addition, the 
numbers of subjects who received IIP at Visit 2, discontinued and completed the study will be 
tabulated. Primary reasons for discontinuation of study IIP will be listed and tabulated. 
11.4.4 
Efficacy Evaluation 
As indicated in Section 7, the first component of the co-primary endpoint is the percentage of 
subjects with sufficiently avid lesion(s) to be identified as a sstr2 positive lesion. This will be a 
simple percentage calculation (number of subjects in sstr2 positive population / number of 
subjects in 68Ga-OPS202 screened population). The second component of the co-primary 
efficacy variable is the differences in the number of lesions detected by 68Ga-OPS202 between 
the three PET acquisition timepoints (0.5, 1 and 2 hours) in the primary breast lesions. The 
second component of the co-primary efficacy variable will be summarised by each of the three 
PET acquisition timepoints (0.5, 1 and 2 hours). The results could identify that one, two or all 
three timepoints have equal validity for future studies in this population. 
As indicated in Section 7, the secondary efficacy variables are the variables measured at Visit 
2 after the i.v. administration of the IIP, listed below: 
Key Secondary Endpoint: 
• 
Differences in the number of lesions detected by 68Ga-OPS202 between the three PET 
acquisition timepoints (0.5, 1 and 2 hours) and reader interpretation of optimal image(s) 
in nodular and metastatic lesions. Significant uptake of 68Ga-OPS202 for the evaluation 
of a lesion is an avid lesion defined by the blinded readers at one of the acquisition 
timepoints as an easily identifiable lesion radiologically, where there has been clear focal 
uptake of 68Ga-OPS202 and 1.5-fold or greater uptake than in the non-tumoural liver and 
lung parenchyma. 
• 
The SUVmean and SUVmax in the primary lesion between each of the three timepoints, 
measured in the most avid lesions (using the 68Ga-OPS202 scans).  This is assessed by 


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the tumour-to-background ratio in the primary tumour and each of the major anatomic 
sites (liver, lymph nodes, bone, lungs and brain); the background consists of 
non-tumoural liver parenchyma or aortic blood where sufficient liver is not available. 
Identification of lesions to be used will be made by one of the two primary readers.  
Other Secondary Endpoints: 
• 
Differences in relative lesion counts as a ratio of the number of lesions detected by 
68Ga-OPS202/ceCT at 0.5, 1 and 2 hours post dose respectively, compared to the number 
of lesions assessed by standard-of-truth (descriptive analyses). The standard-of-truth is 
the 18F-FDG-PET/CT scan images acquired at any time during the study period 
(including the Screening period). This will be calculated by (number of lesions detected 
by 68Ga-OPS202) / (number of lesions detected by 18F-FDG-PET). 
• 
Differences of absolute number of lesions between the three PET acquisition timepoints 
detected in each of the following anatomic sites: 
- 
Lymph nodes  
- 
Liver  
- 
Axial/appendicular skeleton  
- 
Lungs 
- 
Brain 
The second component of the co-primary and appropriate secondary endpoints will also be 
evaluated on a radioactivity dose MBq/kg of body weight. 
The secondary endpoints will be summarised by each of the three PET acquisition timepoints 
(0.5, 1 and 2 hours). 
Exploratory Endpoints: 
• 
Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging of breast cancer expressing 
sstr2 positive by both subject-based and lesion-based analysis compared to standard-of-
truth 
• 
SNR calculated from lesion-free volume of interest (VOI) in the liver: SUVmean/SUVSD 
at the three PET acquisition timepoints 
• 
Estimated correlation in terms of number of avid lesions between 68Ga-OPS202 PET at 
the agreed “optimum timepoint” and 18F-FDG-PET  
• 
Estimated 
correlation 
between 
68Ga-OPS202 PET 
uptake 
and 
results 
of 
immunohistochemistry staining of sstr2 of the primary tumour. 
For further details on efficacy endpoints, refer to Section 7 and the Imaging Review Charter 
(IRC). 
11.4.5 
Adjustment for Country/Centre Effect 
Not applicable. 
11.4.6 
Safety Evaluation 
All AEs will be coded according to the MedDRA version (latest version in use) and will be 
classified by MedDRA SOC and PT. AEs, SAEs, AEs leading to discontinuation of study 
treatment, and AEs leading to death will be summarised and listed by subject, SOC class and 
PT. Adverse events reported by investigators using the NCI-CTCAE classification (version 5.0) 
will be coded using MedDRA dictionary (latest available version). 


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Incidence of all reported AEs and SAEs will be tabulated. In addition, summary tables will be 
presented by maximum intensity, drug relationship and AEs associated with premature 
withdrawal of study medication. 
Concomitant medication will be coded by using WHO Drug Dictionary (WHO-DD) (latest 
available version) and will be summarised. 
Summary statistics (mean, median, SD and range as appropriate) will be presented for vital 
signs (including blood pressure and heart rate), ECG parameters, clinical laboratory tests etc. 
at each assessment with change from Baseline. For laboratory data, abnormal values will be 
flagged in the data listings and a list of clinically significant abnormal values will be presented. 
Clinically significant ECG findings will also be flagged. Shift tables will be presented of the 
number and percentage of subjects with low, normal or high values and normal or abnormal 
exams. 
Summary incidence tables will be provided classified by SOC, PT, and associated NCI-CTCAE 
worst grade. In the event of multiple occurrences of the same AEs being reported by the same 
subject, the maximum intensity (Grade 5 > Grade 4 > Grade 3 > Grade 2 > Grade 1 > missing 
> not applicable) will be chosen.  
Haematological and biochemistry toxicities will be recorded and graded according to the 
NCI-CTCAE criteria. The NCI-CTCAE grade 3 and 4 haematology and biochemistry 
parameters by subject and by cycle will be listed. For WBC, neutrophils, platelets and 
haemoglobin, with associated grade 3 or 4 toxicities, nadir and day to nadir will be calculated. 
11.5 
Subgroup Analyses 
Not applicable. 
11.6 
Interim Analyses 
No interim analysis will be performed. 


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12 
DIRECT ACCESS TO SOURCE DATA AND DOCUMENTS 
Authorised personnel from external CAs and sponsor-authorised Quality Assurance personnel 
may carry out inspections and audits. The purpose of an audit is to ensure that ethical, regulatory 
and quality requirements are fulfilled in all studies performed by the sponsor. 
Sponsor-delegated Clinical Research Associates will have access to source data and documents 
for source data verification purposes during monitoring visits. 
Auditors and inspectors must have direct access to study documents and site facilities as 
specified in Section 13.4, and to any other locations used for the purpose of the study in question 
(e.g. laboratories). 
In the event of the site being notified directly of a regulatory inspection, the investigator must 
notify the sponsor’s representative as soon as possible, to assist with preparations for the 
inspection. 
 


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13 
QUALITY CONTROL AND QUALITY ASSURANCE 
13.1 
Protocol Amendments and Protocol Deviations and Violations 
13.1.1 
Protocol Amendments 
No changes from the final approved (signed) protocol will be initiated without the prior written 
approval or favourable opinion of a written amendment by the IEC, except when necessary to 
eliminate immediate safety concerns to the subjects or when the change involves only logistics 
or administration. In the event that an amendment to this protocol is required, it will be 
classified into one of the following three categories: 
• 
Non-substantial amendments are those that are not considered ‘substantial’ 
(e.g. administrative changes) and as such only need to be notified to the IECs or 
regulatory authorities for information purposes. 
• 
Substantial amendments are those considered ‘substantial’ to the conduct of the clinical 
study where they are likely to have a significant impact on: 
- 
the safety or physical or mental integrity of the subjects; 
- 
the scientific value of the study; 
- 
the conduct or management of the study; or 
- 
the quality or safety of the study drug used in the study. 
Substantial amendments must be submitted to and approved by the IECs and relevant 
regulatory authorities, according to local regulations, prior to implementing changes. 
Urgent amendments are those that require urgent safety measures to protect the study subjects 
from immediate hazard and as such may be implemented immediately by the sponsor with 
subsequent IECs and regulatory authority notification, forthwith. 
The principal investigator and the sponsor will sign the protocol amendment. 
13.1.2 
Protocol Deviations 
All protocol deviations will be identified and recorded by the sponsor or sponsor’s 
representative.  
A major protocol deviation is any significant divergence from the protocol, i.e. nonadherence 
on the part of the subject, the investigator, or the sponsor to protocol-specific 
inclusion/exclusion criteria, primary objective evaluation criteria, and/or GCP guidelines. 
Generally, a protocol deviation qualifies as major if: 
• 
The deviation has harmed or posed a significant or substantive risk of harm to the 
research subject 
• 
The deviation compromises the scientific integrity of the data collected for the study 
• 
The deviation is a willful or knowing breach of human subject protection regulations, 
policies, or procedures on the part of the investigator(s) 
• 
The deviation involves a serious or continuing noncompliance with any applicable 
human subject protection regulations, policies, or procedures 
• 
The deviation is inconsistent with Ipsen’s research, medical and ethical principles. 
See Section 11.1.2 for details on the impact of major protocol deviations on the inclusion of 
subjects in each analysis population. 
A minor protocol deviation is any significant divergence from the protocol that does not impact 
the study results. 


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As a matter of policy, the sponsor will not grant exceptions to protocol specific entry criteria to 
allow subjects to enter a study. If under extraordinary circumstances such action is considered 
ethically, medically, and scientifically justified for a particular subject, prior approval from the 
sponsor and the responsible IRB/IEC, in accordance with the Standard Operating Procedure 
(SOP), is required before the subject will be allowed to enter the study. If investigative centre 
personnel learn that a subject who did not meet protocol eligibility criteria was entered in a 
study (a protocol violation), they must immediately inform the sponsor. Such subjects will be 
discontinued from the study, except in an exceptional instance following review and written 
approval by the sponsor and the responsible IRB/IEC, according to the applicable SOP. 
13.2 
Information to Study Personnel 
To ensure accurate, complete and reliable data, the sponsor or its representatives will provide 
instructional material to the study sites, as appropriate. A study initiation visit will be conducted 
prior to screening start to instruct the investigators and study coordinators. This session will 
give instruction on the protocol, the completion of the CRF and all study procedures. The 
investigator is responsible for giving information about the study to all staff members involved 
in the study or in any element of subject management, both before starting any study procedures 
and during the course of the study (e.g. when new staff become involved, or new information 
becomes available). The investigator must assure that all study staff members are qualified by 
education, experience, and training to perform their specific responsibilities. These study staff 
members must be listed on the study centre authorisation form, which includes a clear 
description of each staff member’s responsibilities. This list must be updated throughout the 
study, as necessary. 
The study monitor is responsible for explaining the protocol to all study staff, including the 
investigator, and for ensuring their compliance with the protocol. Additional information will 
be made available during the study when new staff become involved in the study and as 
otherwise agreed upon with either the investigator or the study monitor. 
13.3 
Study Monitoring 
The investigator is responsible for the validity of all data collected at the site. 
The sponsor is responsible for monitoring these data to verify that the rights and wellbeing of 
subjects are protected, that study data are accurate (complete and verifiable to source data) and 
that the study is conducted in compliance with the protocol, GCP and regulatory requirements. 
Sponsor assigned monitors will conduct regular site visits. The investigator will allow direct 
access to all relevant files (for all subjects) and clinical study supplies (dispensing and storage 
areas) for the purpose of verifying entries made in the eCRF, and assist with the monitor’s 
activities, if requested. Adequate time and space for monitoring visits should be made available 
by the investigator. 
The site must complete the eCRFs on an ongoing basis allow regular review by the study 
monitor, both remotely by the internet and during site visits. The central study monitor at the 
sponsor will use functions of the electronic data capture (EDC) system to address any queries 
raised while reviewing the data entered by the study site personnel in a timely manner. 
Whenever a subject name is revealed on a document required by the sponsor (e.g. laboratory 
printouts) the name must be blacked out permanently by the site personnel, leaving the initials 
visible, and annotated with the subject number as identification. 


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13.4 
Audit and Inspection 
Authorised personnel from external CAs and the sponsor’s authorised Quality Assurance 
personnel may carry out inspections and audits (see Section 12). 
13.5 
Data Quality Assurance 
Monitored eCRFs will be reviewed (secondary monitoring) by the assigned Data Management 
group for completeness, consistency, legibility and protocol compliance. 
Reasons should be given on the relevant eCRF for any missing data. Any electronic queries and 
items not adequately explained will require additional electronic manual queries to be raised to 
the investigator by the monitor or data manager for clarification/correction. The investigator 
must ensure that queries are dealt with promptly. All data changes and clarifications can be 
viewed in the audit trail function of the eCRF. 


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14 
ETHICS 
14.1 
Compliance with Good Clinical Practice and Ethical Considerations 
This study will be conducted in compliance with IECs/IRBs, informed consent regulations, the 
Declaration of Helsinki and ICH GCP Guidelines. 
In addition, this study will adhere to all local regulatory requirements.  
Before initiating a study, the investigator/institution should have written and dated 
approval/favourable opinion from the IEC for the study protocol/amendment(s), written 
informed consent form, any consent form updates, subject emergency study contact cards, 
subject recruitment procedures (e.g. advertisements), any written information to be provided to 
subjects and a statement from the IEC that they comply with GCP requirements. The IEC 
approval must identify the protocol version as well as the documents reviewed. 
After IEC approval, changes will require a formal amendment. Once the study has started, 
amendments should be made only in exceptional circumstances. Changes that do not affect 
subject safety or data integrity are classified as administrative changes and generally do not 
require ethical approval. If ethically relevant aspects are concerned, the IEC must be informed 
and, if necessary, approval sought prior to implementation. Ethical approval on administrative 
changes will be obtained if required by local/site IEC. 
14.2 
Informed Consent for Participation in the Study 
Prior to study entry, the investigator, or a person designated by the investigator, will explain 
the nature, purpose, benefits and risks of participation in the study to each subject, subject’s 
legally acceptable representative or impartial witness. Written informed consent must be 
obtained prior to the subject entering the study (before initiation of any study-related procedure 
and administration of the IIP). Sufficient time will be allowed to discuss any questions raised 
by the subject. 
The sponsor will provide a sample informed consent form. The final version-controlled form 
must be agreed to by the sponsor, and the IEC/IRB and must contain all elements included in 
the sample form, in language readily understood by the subject. Each subject’s original consent 
form, personally signed and dated by the subject or by the subject’s legally acceptable 
representative, and by the person who conducted the informed consent discussion, will be 
retained by the investigator. The investigator will supply subjects with a copy of their signed 
informed consent. 
The consent form may need to be revised during the study following a protocol amendment that 
includes important new information relevant to the safety of the subject. In this instance 
approval should always be given by the IEC/IRB. It is the investigator’s responsibility to ensure 
that all subjects subsequently entered into the study and those currently in the study sign the 
amended form. This is documented in the same way as previously described. Subjects who have 
completed the study should be informed of any new information that may impact on their 
welfare/wellbeing. 
The investigator should, with the consent of the subject, inform the subject’s primary physician 
about their participation in the clinical study. 


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14.3 
Health Authorities and Independent Ethics Committees/Institutional Review 
Boards 
As required by local regulations, the sponsor’s Regulatory Affairs group will ensure all legal 
regulatory aspects are covered, and obtain approval of the appropriate regulatory bodies, prior 
to study initiation in regions where an approval is required. 
The following documents should be submitted to the relevant ethics committee(s) (EC) for 
review and approval to conduct the study (this list may not be exhaustive): 
• 
Protocol/amendment(s) approved by the sponsor, 
• 
Currently applicable IB or package labelling, 
• 
Relevant investigator’s curriculum vitae, 
• 
Subject information and informed consent document(s) and form(s), 
• 
Subject emergency study contact cards, 
• 
Recruitment procedures/materials (advertisements), if any. 
The EC(s) will review all submission documents as required, and a written favourable opinion 
for the conduct of the study should be made available to the investigator before initiating the 
study. This document must be dated and clearly identify the version number(s) and date(s) of 
the documents submitted/reviewed and should include a statement from the EC that they 
comply with GCP requirements. 
The study may begin at the investigative site(s) only after receiving this dated and signed 
documentation of the EC approval or favourable opinion. 
During the study, any update to the following documents will be sent to the EC either for 
information, or for review and approval, depending on how substantial the modifications are: 
(1) IB; (2) reports of SAEs; (3) all protocol amendments and revised informed consent(s), if 
any. 
At the end of the study, the EC will be notified about the study completion. 
14.4 
Confidentiality Regarding Study Subjects 
The investigator must assure that the privacy of the subjects, including their personal identity 
and all personal medical information, will be maintained at all times. In eCRFs and other 
documents or image material submitted to the sponsor, subjects will be identified not by their 
names, but by an identification code (e.g. initials and identification number). 
Personal medical information may be reviewed for the purpose of verifying data recorded in 
the eCRF. This review may be conducted by the study monitor, properly authorised persons on 
behalf of the sponsor, the quality assurance unit, or regulatory authorities. Personal medical 
information will always be treated as confidential. 


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15 
DATA HANDLING AND RECORD KEEPING 
15.1 
Data Recording of Study Data 
In compliance with GCP, the medical records/medical notes, etc, should be clearly marked and 
permit easy identification of a subject’s participation in the specified clinical study. 
The investigator must record all data relating to protocol procedures, IIP administration, 
laboratory data, safety data in the eCRFs provided for the study. The investigator, by 
completing the signature log, may formally designate authority to complete eCRFs to 
appropriately qualified staff having certified user access to the eCRF.  
The investigator must, as a minimum, provide an electronic signature (e-signature) to each case 
report book to attest to the accuracy and completeness of all the data. If any changes are made 
to the eCRF, after a form has been locked and electronically signed, the investigator will be 
required to perform an additional e-signature authorising agreement with any new information 
or changes to the eCRF. 
All corrections in the eCRF will be automatically tracked and a reason for change is always 
required. In the eCRF, the audit trail function will allow the changes made to be viewed on each 
item entered. 
15.2 
Data Management 
An EDC system will be utilised for collecting subject data. Each site is required to have a 
computer and internet connection available for site entry of clinical data. All entries in the eCRF 
will be done under the electronic signature of the person performing the action. This electronic 
signature consists of an individual and confidential username and password combination. It is 
declared to be the legally binding equivalent of the handwritten signature. Only sponsor 
authorised users will have access to the eCRF as appropriate to their study responsibilities. 
Users must have successfully undergone software application training prior to entering data into 
the eCRF. 
Data management will be conducted by a CRO, directed by the sponsor’s data management 
department. All data management procedures will be completed in accordance with the 
contracted CRO standard operating procedures (SOPs), unless otherwise specified. Prior to data 
being received in-house at the assigned CRO, they will be monitored at the investigator site; 
for further details please see Section 13.3 Monitoring Procedures. The eCRF and other data 
documentation removed from the investigator site(s) will be tracked by the CRO and the 
monitor. 
The sponsor will ensure that an appropriate eCRF is developed to capture the data accurately, 
and suitable queries are raised to resolve any missing or inconsistent data. The investigator will 
receive their data, from the clinical study, in an electronic format (PDF files) which will be an 
exact copy of the eCRF, and will include the full audit trail, for archiving purposes and future 
reference. 
Any queries generated during the data management process will also be tracked by the 
contracted data management CRO or will be raised within the EDC system. It is the central 
study monitor’s responsibility to ensure that all queries are resolved by the relevant parties. 
The sponsor will also ensure that SAE data collected in the eCRF are consistent with 
information provided to the sponsor’s pharmacovigilance department (and vice versa).  
The coding of AEs, medical history, surgical procedures concomitant medication, procedure 
and non-drug therapy terms will be performed centrally by the specialised CRO, directed by 
the sponsor’s Biometry Group, and reviewed and approved by the sponsor. Concomitant 


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medications will be coded using WHO-DD (latest available version) and AEs/medical history 
terms will be coded using MedDRA (latest available version). 
Only data from enrolled subjects will be reported in the eCRFs and collected in the sponsor’s 
database. 
For screen failure subjects, only the Unique Subject Identifier, the date of informed consent 
signature, the reason why the subject failed screening and the potential AEs which occurred 
during the screening phase will be reported in the eCRFs and collected in the sponsor’s 
database. 
15.3 
Record Archiving and Retention 
During the pre-study and initiation visits, the monitor must ensure the archiving facilities are 
adequate and archiving/retention responsibilities of the investigator have been discussed.  
Study documents should be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or planned marketing applications 
in an ICH region (that is at least 15 years) or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the product. However, these documents should be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the sponsor. The investigator should take measures to prevent accidental or 
premature destruction of these documents. The final archiving arrangements will be confirmed by 
the monitor when closing out the site. The sponsor will inform the investigator, in writing, as to 
when these documents no longer need to be retained. 
If the principal investigator relocates or retires, or otherwise withdraws his/her responsibility 
for maintenance and retention of study documents, the sponsor must be notified (preferably in 
writing) so that adequate provision can be made for their future maintenance and retention. 


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16 
FINANCING AND INSURANCE 
16.1 
Contractual and Financial Details 
The investigator (and/or, as appropriate, the hospital administrative representative) and the 
sponsor will sign a clinical study agreement prior to the start of the study, outlining overall 
sponsor and investigator responsibilities in relation to the study. Financial remuneration will 
cover the cost per included subject, based on the calculated costs of performing the study 
assessments in accordance with the protocol, and the specified terms of payment will be 
described in the contract. The contract should describe whether costs for pharmacy, laboratory 
and other protocol-required services are being paid directly or indirectly. 
Financial Disclosure Statements will need to be completed, as requested by FDA 21 CFR 
Part 54. 
16.2 
Insurance, Indemnity and Compensation 
The sponsor will provide Product Liability insurance for all subjects included in the clinical 
study. Where required, a hospital-specific indemnity agreement will be used. 


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17 
REPORTING AND PUBLICATIONS OF RESULTS 
17.1 
Publication Policy 
The sponsor encourages acknowledgement of all individuals/organisations involved in the 
funding or conduct of the study, including medical writers or statisticians subject to the consent 
of each individual and entity concerned, including acknowledgement of the sponsor. 
The results of this study may be published or communicated to scientific meetings by the 
investigators involved in the study. For multicentre studies, a plan for scientific publication and 
presentation of the results may be agreed and implemented by the study investigators. The 
sponsor requires that reasonable opportunity be given to review the content and conclusions of 
any abstract, presentation, or paper before the material is submitted for publication or 
communicated. This condition also applies to any amendments that are subsequently requested 
by referees or journal editors. The sponsor will undertake to comment on the draft documents 
within the time period agreed in the contractual arrangements, including clinical trial 
agreements, governing the relationship between the sponsor and authors (or the author’s 
institution). Requested amendments will be incorporated by the author, provided they do not 
alter the scientific value of the material. 
If patentability would be adversely affected by publication, this will be delayed until (i) a patent 
application is filed for the content of the publication in accordance with applicable provisions 
of the clinical trial agreement concerned, (ii) the sponsor consents to the publication, or (iii) the 
time period as may be agreed in the contractual arrangements, including clinical trial 
agreements, governing the relationship between the sponsor and authors (or authors’ institution) 
after receipt of the proposed publication by the sponsor, whichever of (i), (ii) or (iii) occurs 
first. 
The author undertakes to reasonably consider the sponsor's request for delay to the proposed 
publication should the sponsor reasonably deem premature to publish the results obtained at 
this stage of the study. 
17.2 
Clinical Study Report 
A final clinical study report (CSR) will be prepared according to the ICH guideline on structure 
and contents of CSRs. A final CSR will be prepared where any subject has signed informed 
consent, regardless of whether the study is completed or prematurely terminated. Where 
appropriate an abbreviated report may be prepared. The CSR will comply with any applicable 
regulatory requirements, national laws in force and will be in English. 


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18 
REFERENCES 
1. 
OctreoscanTM 
Prescribing 
Information. 
[available 
at: 
https://www.drugs.com/pro/octreoscan.html, accessed 01 November 2017]. 
2. 
NETSPOT® 
Prescribing 
Information. 
[available 
at: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208547s000lbl.pdf, 
accessed 01November 2017]. 
3. 
Summary of Product Characteristics SomaKit TOC 40 micrograms kit for 
radiopharmaceutical 
preparation. 
[available 
at: 
http://www.adacap.com/wp-
content/uploads/2017/05/emea-combined-h-4140-en.pdf, accessed 01 December 2017]. 


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19 
LIST OF APPENDICES 
 


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Appendix 1 Protocol Summary of Changes - Amendment 1.0 
 


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STUDY NUMBER 
D-FR-01070-003 
PROTOCOL TITLE: 
A non-randomised phase II study to evaluate the 
optimal uptake time of 68Ga-OPS202 as a sstr2 
positive PET imaging agent in subjects with newly 
diagnosed breast cancer 
AMENDED PROTOCOL VERSION 
NUMBER & DATE 
Version 2.0, Amendment 1.0; 27 June 2018 
THE FOLLOWING AMENDMENTS ARE PROPOSED: 
Version Date 
02 February 2018 
27 JUNE 2018 
Page  
Section 
WAS 
IS 
1 
Title page Version 1.0; 02 February 2018 
Version 2.0, Amendment 1.0; 
27 June 2018 
 
 
Sponsor Signatory:  
 
Sponsor Signatory:  
 
1 
Title page Emergency Contact: 
 
Ipsen Biopharm Ltd, 102 Park Drive, 
Milton Park, Abingdon, OX14 4RY, 
UK. 
Tel:  
 
Mobile:
  
The person listed above is designated 
by the sponsor as the first point of 
contact for emergency situations. 
 
For serious adverse events (SAEs) 
reporting: 
Email: 
 
 
Pharmacovigilance/Emergency 
Contact: 
 
, Ipsen 
Innovation ZI de Courtaboeuf - 5 
avenue du Canada - 91940 Les Ulis 
- France 
Phone: 
 
Mobile: 
 
The person listed above is 
medically qualified and 
designated by the sponsor as the 
first point of contact for 
emergency situations. 
For serious adverse events (SAEs) 
reporting:  
Email 
address 
(preferably): 
  
Fax: 
 
4 
Synopsis 
Planned study period: 
FPI: April 2018 - LPO: December 
2018 
Planned study period: 
FPI: July 2018 - LPO: December 
2018 
4 
Synopsis 
Study hypothesis: The update of 
68Ga-OPS202 does not vary according 
to PET acquisition time within a range 
of 1.5 hours in subjects with sstr2 
positive newly diagnosed breast 
cancer, taking into account the 68Ga 
decay. 
Study hypothesis: The uptake of 
68Ga-OPS202 
does 
not 
vary 
according to PET acquisition time 
within a range of 1.5 hours in 
subjects with sstr2 positive newly 
diagnosed breast cancer, taking 
into account the 68Ga decay. 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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5 
Synopsis 
Methodology: 
Study design: 
... 
Three PET images will be acquired at 
0.5, 
1.0 
and 
2.0 
hours 
post 
68Ga-OPS202 
injection 
and 
one 
contrast enhanced (ce) CT scan will 
also be acquired at 2 hours post PET 
timepoint. All images will be sent to 
an imaging core laboratory (ICL) for 
central blinded reading by two 
independent 
experienced 
radiologists/nuclear 
medicine 
physicians and a third for adjudication 
of discordances. The readers will be 
specifically trained for this protocol. 
18F-FDG-PET scan, which is part of 
routine clinical diagnosis, will be 
acquired at any time during the study 
period 
(including 
the 
Screening 
period), according to the investigator 
site’s standards. 18F-FDG-PET scan 
images will also be sent to the ICL. 
Methodology: 
Study design: 
... 
Three PET acquisitions will be 
performed at 0.5, 1.0 and 2.0 
hours post 68Ga-OPS202 injection. 
18F-FDG-PET scan, which is part 
of routine clinical diagnosis, will 
be acquired at any time during the 
study 
period 
(including 
the 
Screening period), according to the 
investigator site’s standards.  
A 
single 
contrast 
enhanced 
computed tomography (ceCT) 
scan is required for the study.  
This can be acquired after either 
of the two PET scans (18F-FDG-
PET or 68Ga-OPS202 post the 2-
hour acquisition).  Thus, only 
one ceCT scan is required to 
minimise radiation dose.  Low-
dose CT scans will be acquired 
for the other PET scans when the 
ceCT is not obtained. 
All 
images 
(68Ga-OPS202 
PET/CT scans, 
18F-FDG-PET 
scan, and ceCT scan) will be sent 
to an imaging core laboratory 
(ICL) for central blinded reading. 
 
5 
Synopsis 
Duration of participation for a 
subject:  
... 
• 
Visit 2: a single intravenous 
(i.v.) injection of a fixed activity 
range of 68Ga-OPS202 on Day 1 
followed by PET imaging at 0.5, 
1 and 2 hours ±5 minutes post 
dosing, and a ceCT scan 
immediately after the 2-hour 
PET timepoint 
• 
Visit 3: a follow-up visit at Day 
14 (±3 days) for evaluation of 
safety. 
Duration of participation for a 
subject:  
... 
• 
Visit 2 (Day 1): a single 
intravenous (i.v.) injection of a 
fixed activity range of 
68Ga-OPS202 followed by 
PET acquisitions at 0.5, 1 and 
2 hours ±10 minutes post 
dosing (see Methodology 
Section above) 
• 
Visit 3: a follow-up visit at Day 
14 (±3 days) for evaluation of 
safety. Within the study an 
18F-FDG-PET scan and also 


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a ceCT scan must also be 
acquired. 
5-6 
Figure S1 
Figure contains strata per invasive 
stage. 
 
Note: Approximately 54 subjects will 
be screened to receive IIP to identify 
16 sstr2 evaluable subject scans: 
eight subjects with early disease and 
eight subjects with advanced disease. 
Strata removed from figure and 
footnotes updated. 
 
 
Note: Approximately 54 subjects 
will be screened to receive IIP to 
identify 
16 
sstr2 
positive 
evaluable subject scans. 
6 
Synopsis 
Assessments: 
The Screening Visit (Visit 1) will be 
performed within 14 days prior to the 
first 68Ga OPS202 administration. At 
Screening, after obtaining written 
informed consent, the investigator 
will collect all the information 
required to confirm the subject 
eligibility including medical and 
surgical 
history, 
physical 
examination, 
laboratory 
tests 
(haematology, blood chemistry and 
urinalysis) and tumour histopathology 
if available. Tumour biopsy, which is 
not a prerequisite for inclusion, is 
routinely performed for confirmation 
and staging of the disease, as well as 
classification according to hormone 
receptor status and human epidermal 
growth factor receptor 2 (HER2) 
status. 
For 
the 
study, 
paraffin 
embedded slides are required for the 
evaluation of sstr2 expression by 
immunohistochemistry staining. 
Subjects’ eligibility will be re-
checked by the investigator at 
Baseline/Day 1 (Visit 2) before 
administration of the IIP. If eligibility 
is re-confirmed, the subject will 
receive one injection of 68Ga-OPS202 
followed by whole body PET imaging 
at 0.5, 1 and 2 hours after the injection 
of the IIP. A single ceCT scan will be 
performed after the 2-hour PET scan, 
according 
to 
the 
site 
standard 
procedure for chest, abdomen, pelvis 
and brain.  
Assessments: 
The Screening Visit (Visit 1) will 
be performed within 14 days prior 
to 
the 
first 
68Ga-OPS202 
administration. At Screening, after 
obtaining 
written 
informed 
consent, 
the 
investigator 
will 
collect all the information required 
to confirm the subject eligibility 
including medical and surgical 
history, physical examination and 
vital 
signs, 
laboratory 
tests 
(haematology, blood chemistry and 
urinalysis) 
and 
tumour 
histopathology 
if 
available. 
Tumour biopsy blocks or slides 
are required for the evaluation of 
sstr2 
expression 
by 
immunohistochemistry 
staining 
with the anatomical location of 
the lesion(s) indicated to be 
matched with the 68Ga-OPS202 
PET/CT images. 
Subjects’ eligibility will be re-
checked by the investigator at 
Baseline/Day 1 (Visit 2) before 
administration of the IIP. If 
eligibility is re-confirmed, the 
subject will receive one injection 
of 
68Ga-OPS202 followed by 
whole body PET imaging at 0.5, 1 
and 2 hours after the injection of 
the IIP. An 18F-FDG-PET scan 
will be acquired at any time 
during 
the 
study 
period 
(including the Screening period), 
according to the investigator 


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Subjects 
may 
be 
hospitalised 
overnight 
upon 
completion 
of 
68Ga-OPS202 PET/CT scan at the 
discretion of the investigator. 
site’s standards. If the 18F-FDG-
PET scan is performed before 
the informed consent signature, 
subject approval is required for 
using this image set. 
A single ceCT scan will be 
performed according to the site 
standard procedure for chest, 
abdomen, pelvis and brain. This 
can be acquired after either of 
the 
two 
PET 
scans 
(18F-FDG-PET or 68Ga-OPS202 
post the 2-hour acquisition). 
Low-dose CT scans will be 
acquired with PET scans when 
necessary 
for 
attenuation 
correction. 
Subjects may be hospitalised 
overnight upon completion of 
68Ga-OPS202 PET/CT scans at the 
discretion of the investigator. 
7 
Synopsis 
Independent 
read 
of 
PET/CT 
images: 
This 
is 
an 
open-label 
study. 
Independent readers will evaluate 
68Ga-OPS202 
PET/CT 
and 
18F-FDG-PET images and will be 
blinded to the acquisition time of the 
PET scan, investigator site and 
clinical status of the subject, including 
pathology, 
laboratory, 
medical 
history and physical exam findings. 
Independent readers are specialised 
radiologists and/or nuclear medicine 
physicians who are experienced in 
reading PET/CT scans. To minimise 
inter- and intra-reader variability in 
results, the readers will be specifically 
trained for this protocol. 
Independent read of PET/CT 
images: 
This is a non-randomised open-
label study. Independent readers 
will 
evaluate 
68Ga-OPS202 
PET/CT and 
18F-FDG-PET/CT 
images and will be blinded to the 
acquisition time of the PET scans 
and CT scans, investigator site 
and clinical status of the subject, 
including pathology, laboratory, 
medical history and physical exam 
findings. 
The 
independent 
readers 
are 
specialised 
radiologists 
and/or 
nuclear medicine physicians who 
are experienced in reading PET/CT 
scans.. To minimise inter- and 
intra-reader variability in results, 
the readers will be specifically 
trained for this protocol. Two 
readers will read 100% of all the 
images and third will adjudicate 
any differences. 
7 
Synopsis 
Number of subjects planned:  
Number of subjects planned:  


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It is anticipated that a total of 54 
subjects will be enrolled in the study 
for 68Ga-OPS202 screening, to obtain 
around 16 sstr2 evaluable subjects. 
Considering the estimated prevalence 
of sstr2 overexpression in breast 
cancer, the overall number of subjects 
to be screened with 68Ga-OPS202 in 
the study will be approximately 54. 
However, when the ICL identifies 16 
sstr2 evaluable subject scans, with 
eight subjects having early disease 
and eight subjects advanced disease, 
the study will be complete. 
This estimation of 16 sstr2 evaluable 
subjects is considered appropriate for 
a descriptive analysis and it is not 
based on a formal statistical sample 
size calculation. In the event that a 
subject misses an imaging exam 
and/or measurement relevant to the 
primary and key secondary endpoints, 
an additional subject will be recruited 
as a replacement to ensure an 
adequate sample size in the sstr2 
evaluable set. 
Considering 
the 
estimated 
prevalence of sstr2 overexpression 
in breast cancer, it is anticipated 
that a total of approximately 54 
subjects will be enrolled in the 
study for 68Ga-OPS202 PET/CT 
imaging, to obtain 16 sstr2 
positive 
breast cancer 
(BC) 
evaluable 
subjects. 
However, 
when the ICL identifies 16 sstr2 
positive evaluable subject scans, 
with a minimum of two subjects 
with advanced disease, the study 
will be complete.  
Futility Stopping Rules 
If less than three sstr2 positive 
evaluable subject scans out of 30 
consecutive subjects screened 
with 68Ga-OPS202 PET/CT, or 
less than 8 out of 50, the study 
will be stopped.  
The 
Sponsor 
may 
consider 
stopping 
subject 
recruitment 
and revisit the study design with 
possible termination of the study 
when justified. 
8-9 
Synopsis 
Test 
product, 
dose, 
mode 
of 
administration: 
... 
The IIP is a solution for injection 
prepared prior to administration from 
a radiolabelling "cold" kit and a 
68Ge/68Ga-generator. 
The 
radiolabelling kit consists of two 
vials; one containing lyophilised 
OPS202 and excipients and a second 
containing 
a 
solution 
for 
reconstitution. 
Test product, dose, mode of 
administration: 
... 
The IIP is a solution for injection 
prepared prior to administration 
from a radiolabelling "cold" kit and 
a 
68Ge/68Ga-generator. 
The 
radiolabelling kit consists of two 
vials; one containing 50 μg 
lyophilised OPS202 and excipients 
and a second containing a solution 
for reconstitution. 
9 
Synopsis 
Reference therapy, dose and mode 
of administration:  
Comparator compound/placebo: 
In this study, there is no comparison 
with a reference-imaging product. 
The primary statistical analyses will 
evaluate the differences (if any) 
between the three different timepoints 
Reference therapy, dose and 
mode of administration:  
Comparator compound/placebo: 
In 
this 
study, 
there 
is 
no 
comparison with a reference-
imaging product. The primary 
statistical analyses will evaluate 
the differences (if any) between the 
three different scan acquisition 


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of the 68Ga-OPS202 PET and the 
PET/CT imaging acquisition. 
timepoints of the 
68Ga-OPS202 
PET. 
9 
Synopsis 
Criteria for evaluation (endpoints): 
Efficacy: 
The primary and secondary imaging 
endpoints will be read by third-party 
independent readers. Most of the 
reading will be conducted in a blinded 
manner by two primary readers and a 
third to adjudicate any differences. 
Co-primary and secondary endpoints 
will be measured in the primary 
tumour and key organs consisting of 
liver, lymph nodes, bone, lungs and 
brain. 
Co-primary efficacy endpoints and 
evaluation 
• 
Percentage of subjects with 
sufficiently avid lesion(s) to be 
identified as a sstr2 positive lesion. 
(Avid is defined by the blinded 
readers at one of the timepoints as an 
easily 
identifiable 
lesion 
radiologically, where there has been 
clear focal uptake of 68Ga-OPS202) 
Criteria 
for 
evaluation 
(endpoints): 
Efficacy: 
The 
primary 
and 
secondary 
imaging endpoints will be read by 
third-party independent readers. 
Co-primary 
and 
secondary 
endpoints will be measured in the 
primary tumour and key organs 
consisting of liver, lymph nodes, 
bone, lungs and brain. 
Co-primary efficacy endpoints and 
evaluation 
• 
Percentage 
of 
subjects 
with sufficiently avid lesion(s) to 
be identified as a sstr2 positive 
lesion. (Avid is defined by the 
blinded readers at one of the 
acquisition timepoints as an easily 
identifiable lesion radiologically, 
where there has been clear focal 
uptake of 68Ga-OPS202 and 1.5-
fold or greater uptake than the 
non-tumoural liver and lung 
parenchyma). 
10 
Synopsis 
Key secondary endpoint: 
• 
Differences in the number of 
lesions detected by 
68Ga-OPS202 
between the three PET acquisition 
timepoints (0.5, 1 and 2 hours), and 
reader 
interpretation 
of 
optimal 
image(s) in nodular and metastatic 
lesions. 
• 
Differences at each of the 
three timepoints in SUVmean and 
SUVmax, as measured by the tumour-
to-background ratio in the primary 
tumour and each of the major 
anatomic sites (liver, lymph nodes, 
bone, lungs and brain). 
Key secondary endpoint: 
• 
Differences in the number 
of lesions detected by 
68Ga-
OPS202 between the three PET 
acquisition timepoints (0.5, 1 and 2 
hours), and reader interpretation of 
optimal image(s) in nodular and 
metastatic 
lesions. 
Significant 
uptake of 68Ga-OPS202 for the 
evaluation of a lesion is an avid 
lesion defined by the blinded 
readers at one of the acquisition 
timepoints 
as 
an 
easily 
identifiable lesion radiologically, 
where there has been clear focal 
uptake of 68Ga-OPS202 and 1.5-
fold or greater uptake than in the 
non-tumoural liver and lung 
parenchyma. 


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• 
The SUVmean and SUVmax 
in the primary lesions between 
each of the three timepoints, 
measured in the most avid 
lesions (using the 68Ga-OPS202 
scans). This is assessed by the 
tumour-to-background ratio in the 
primary tumour and each of the 
major anatomic sites (liver, lymph 
nodes, bone, lungs and brain); the 
background 
consists 
of 
non-tumoural liver parenchyma 
or aortic blood where sufficient 
liver 
is 
not 
available. 
Identification of lesions to be 
used will be made by one of the 
two primary readers. 
11 
Synopsis 
Sample 
size 
and 
power 
considerations:   
It is anticipated that a total of 54 
subjects will be enrolled in the study 
for 68Ga-OPS202 screening, to obtain 
around 16 sstr2 evaluable subjects. 
Considering the estimated prevalence 
of sstr2 overexpression in breast 
cancer, the overall number of subjects 
to be screened with 68Ga-OPS202 in 
the study will be approximately 54. 
However, when the ICL identifies 
16 sstr2 evaluable subjects, with eight 
subjects having early disease and 
eight subjects advanced disease, the 
study will be complete. 
This estimation of 16 sstr2 evaluable 
subjects is considered appropriate for 
a descriptive analysis and it is not 
based on a formal statistical sample 
size calculation. In the event that a 
subject misses an imaging exam 
and/or measurement relevant to the 
primary and key secondary endpoints, 
an additional subject will be recruited 
as a replacement to ensure an 
adequate sample size in the sstr2 
evaluable set.  
Sample 
size 
and 
power 
considerations:   
It is anticipated that a total of 
approximately 54 subjects will be 
enrolled in the study for 68Ga-
OPS202 PET/CT imaging, to 
obtain around 16 sstr2 positive BC 
evaluable subjects. Considering the 
estimated prevalence of sstr2 
overexpression in breast cancer, 
the overall number of subjects to be 
screened with 68Ga-OPS202 in the 
study will be over 50. However, 
when the ICL identifies 16 sstr2 
positive evaluable subjects, with a 
minimum of two subjects with 
advanced disease, the study will be 
complete. 
This estimation of 16 sstr2 positive 
BC 
evaluable 
subjects 
is 
considered 
appropriate 
for 
a 
descriptive analysis and it is not 
based on a formal statistical sample 
size calculation. In the event that a 
subject misses an imaging exam 
and/or measurement relevant to the 
primary 
and 
key 
secondary 
endpoints, an additional subject 
will be recruited to ensure an 
adequate sample size in the sstr2 
positive BC evaluable set.  


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18 
 
LIST OF ABBREVIATIONS 
LIST OF ABBREVIATIONS 
Added: 
BC 
Breast cancer 
IRC 
Imaging review charter 
PT 
Preferred term 
23 
2.3 
Study Hypothesis 
The update of 68Ga-OPS202 does not 
vary according to PET acquisition 
time within a range of 1.5 hours in 
subjects with sstr2 positive newly 
diagnosed breast cancer, taking into 
account the 68Ga decay. 
Study Hypothesis 
The uptake of 68Ga-OPS202 does 
not vary according to PET 
acquisition time within a range of 
1.5 hours in subjects with sstr2 
positive newly diagnosed breast 
cancer, taking into account the 
68Ga decay. 
24 
3.1 
General Design and Study Schema 
... 
Three PET images will be acquired at 
0.5, 
1.0 
and 
2.0 
hours 
post 
68Ga-OPS202 
injection 
and 
one 
contrast enhanced (ce) CT scan will 
also be acquired at 2 hours post PET 
timepoint. All images will be sent to 
an imaging core laboratory (ICL) for 
central blinded reading by two 
independent experienced radiologists 
and/or nuclear medicine physicians 
and a third for adjudication of 
discordances. The readers will be 
specifically trained for this protocol.  
18F-FDG-PET scan, which is part of 
routine clinical diagnosis, will be 
acquired at any time during the study 
period 
(including 
the 
Screening 
period), according to the investigator 
site’s standards. 18F-FDG-PET scan 
images will also be sent to the ICL. 
...At 
Screening, 
after 
obtaining 
written 
informed 
consent, 
the 
investigator will collect all the 
information required to confirm the 
subject eligibility including medical 
and 
surgical 
history, 
physical 
examination, 
laboratory 
tests 
(haematology, blood chemistry and 
urinalysis) and tumour histopathology 
if available. 
General 
Design 
and 
Study 
Schema 
... 
Three PET images will be acquired 
at 0.5, 1.0 and 2.0 hours post 
68Ga-OPS202 injection.  
18F-FDG-PET scan, which is part 
of routine clinical diagnosis, will 
be acquired at any time during the 
study 
period 
(including 
the 
Screening period), according to the 
investigator site’s standards.  
A single ceCT scan is required 
for the study.  This can be 
acquired following either of the 
two PET scans (FDG-PET or 
68Ga-OPS202 post the 2-hour 
acquisition).  Only one ceCT 
scan is required to minimise 
radiation dose.  Low-dose CT 
scans will be acquired for the 
other PET scans when the ceCT 
is not obtained. For the 68Ga-
OPS202 PET scan a single low 
dose CT scan is preferred for the 
0.5 and 1.0-hour post dosing 
acquisitions. 
All 
images 
(68Ga-OPS202 
PET/CT 
scans, 
18F-FDG-
PET/CT scan, and ceCT scan) 
will be sent to an imaging core 
laboratory 
(ICL) 
for 
central 
blinded reading. See Section 7 and 


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...For the study, paraffin embedded 
slides are required for the evaluation 
of 
sstr2 
expression 
by 
immunohistochemistry 
staining. 
Subjects’ eligibility will be re-
checked by the investigator at 
Baseline/Day 1 (Visit 2) before 
administration of the IIP. If eligibility 
is re-confirmed, the subject will 
receive one injection of 68Ga-OPS202 
followed by whole body PET imaging 
at 0.5, 1 and 2 hours after the injection 
of the IIP. A single ceCT scan will be 
performed after the 2-hour PET scan, 
according 
to 
the 
site 
standard 
procedure for chest, abdomen, pelvis 
and brain. A low dose CT may be 
performed at the 0.5 and/or 1 hour 
PET as well as for the 18F-FDG-PET 
(see the Imaging Review Charter 
(IRC)). 
Subjects 
may 
be 
hospitalised 
overnight upon completion of the 
68Ga-OPS202 PET/CT scan at the 
discretion of the investigator. All 
subjects (either hospitalised or not) 
will attend a consultation on Day 2 for 
a physical examination and laboratory 
tests. 
the Imaging Review Charter 
(IRC) for further details.  
...At Screening, after obtaining 
written informed consent, the 
investigator will collect all the 
information required to confirm the 
subject 
eligibility 
including 
medical 
and 
surgical 
history, 
physical examination and vital 
signs, 
laboratory 
tests 
(haematology, blood chemistry and 
urinalysis) 
and 
tumour 
histopathology if available. 
...For the study, the collection of 
an archived tumour sample (a 
block is preferred over paraffin 
embedded slides) is required for 
the evaluation of sstr2 expression 
by 
immunohistochemistry 
staining. 
Subjects’ eligibility will be re-
checked by the investigator at 
Baseline/Day 1 (Visit 2) before 
administration of the IIP. If 
eligibility is re-confirmed, the 
subject will receive one injection 
of 
68Ga-OPS202 followed by 
whole body PET acquisition at 
0.5, 1 and 2 hours after the 
injection of the IIP. A single ceCT 
scan will be performed according 
to the site standard procedure for 
chest, abdomen, pelvis and brain. 
This can be acquired after either 
of 
the 
two 
PET 
scans 
(18F-FDG-PET or 68Ga-OPS202 
post the 2-hour acquisition). 
Low-dose CT scans will be 
acquired with PET scans when 
necessary 
for 
attenuation 
correction. 
Subjects may be hospitalised 
overnight upon completion of the 
68Ga-OPS202 PET/CT scans at the 
discretion of the investigator. All 
subjects (either hospitalised or not) 
will attend a consultation on Day 2 
for a physical examination, vital 
signs and laboratory tests. Also an 


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18F-FDG-PET scan and ceCT 
scan will be arranged if not 
already acquired. 
25 
3.1 
Figure 1 
Figure contains strata per invasive 
stage. 
 
Note: Approximately 54 subjects will 
be screened to receive IIP to identify 
16 sstr2 evaluable subject scans: eight 
subjects with early disease and eight 
subjects with advanced disease. 
Strata removed from figure and 
footnotes updated. 
 
 
Note: Approximately 54 subjects 
will be screened to receive IIP to 
identify 16 sstr2 positive evaluable 
subject scans. 
25 
3.2 
Primary and Secondary Endpoints 
and Evaluations 
The primary and secondary imaging 
endpoints will be read by third-party 
independent readers. Most of the 
reading will be conducted in a blinded 
manner by two primary readers and a 
third to adjudicate any differences. 
Co-primary and secondary endpoints 
will be measured in the primary 
tumour and key organs consisting of 
liver, lymph nodes, bone, lungs and 
brain. 
Primary 
and 
Secondary 
Endpoints and Evaluations 
The 
primary 
and 
secondary 
imaging endpoints will be read by 
third-party independent readers. 
Co-primary 
and 
secondary 
endpoints will be measured in the 
primary tumour and key organs 
consisting of liver, lymph nodes, 
bone, lungs and brain. 
25 
3.2.1 
Primary Efficacy Endpoint and 
Evaluation 
• 
Percentage of subjects with 
sufficiently avid lesion(s) to be 
identified as a sstr2 positive lesion. 
(Avid is defined by the blinded 
readers at one of the timepoints as an 
easily 
identifiable 
lesion 
radiologically, where there has been 
clear focal uptake of 68Ga-OPS202). 
 
Primary Efficacy Endpoint and 
Evaluation 
• 
Percentage 
of 
subjects 
with sufficiently avid lesion(s) to 
be identified as a sstr2 positive 
lesion. (Avid is defined by the 
blinded readers at one of the 
acquisition timepoints as an easily 
identifiable lesion radiologically, 
where there has been clear focal 
uptake of 68Ga-OPS202 and 1.5-
fold or greater uptake than the 
non-tumoural liver and lung 
parenchyma). 
25 
3.2.2.1 
Key secondary endpoint: 
• 
Differences in the number of 
lesions detected by 
68Ga-OPS202 
between the three PET acquisition 
timepoints (0.5, 1 and 2 hours), and 
reader 
interpretation 
of 
optimal 
image(s) in nodular and metastatic 
lesions. 
Key secondary endpoint: 
• 
Differences in the number 
of lesions detected by 
68Ga-
OPS202 between the three PET 
acquisition timepoints (0.5, 1 and 2 
hours), and reader interpretation of 
optimal image(s) in nodular and 
metastatic 
lesions. 
Significant 


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• 
Differences at each of the 
three timepoints in SUVmean and 
SUVmax, as measured by the tumour-
to-background ratio in the primary 
tumour and each of the major 
anatomic sites (liver, lymph nodes, 
bone, lungs and brain). 
uptake of 68Ga-OPS202 for the 
evaluation of a lesion is an avid 
lesion defined by the blinded 
readers at one of the acquisition 
timepoints 
as 
an 
easily 
identifiable lesion radiologically, 
where there has been clear focal 
uptake of 68Ga-OPS202 and 1.5-
fold or greater uptake than in the 
non-tumoural liver and lung 
parenchyma. 
• 
The SUVmean and SUVmax 
in the primary lesions between 
each of the three timepoints, 
measured in the most avid 
lesions (using the 68Ga-OPS202 
scans). This is assessed by the 
tumour-to-background ratio in the 
primary tumour and each of the 
major anatomic sites (liver, lymph 
nodes, bone, lungs and brain); the 
background 
consists 
of 
non-tumoural liver parenchyma 
or aortic blood where sufficient 
liver 
is 
not 
available. 
Identification of lesions to be 
used will be made by one of the 
two primary readers. 
26 
3.2.4 
Safety Endpoints and Evaluations 
The investigator will report the 
occurrence of any AE throughout the 
study, including clinically significant 
abnormalities in laboratory tests 
(serum chemistry, haematology, and 
urinalysis), vital signs (including 
blood pressure and heart rate) 
measurements, physical examination 
findings 
and 
body 
weight 
measurements at each visit: Screening 
Visit (Visit 1), Baseline Visit (Visit 2; 
Day 1 and Day 2) and End of 
Study/Early Withdrawal Visit (Visit 
3). The electrocardiogram (ECG) 
findings are to be recorded at the 
Screening Visit (Visit 1) and the End 
of Study/Early Withdrawal Visit 
(Visit 3). Relevant medical history 
and 
concomitant 
Safety 
Endpoints 
and 
Evaluations 
The investigator will report the 
occurrence of any AE throughout 
the study and vital signs (including 
blood pressure and heart rate) 
measurements 
at 
each 
visit: 
Screening Visit (Visit 1; Day -14 
to -1), Visit 2 (Day 1), Baseline 
Visit (Visit 2; Day 2) and End of 
Study/Early 
Withdrawal 
Visit 
(Visit 3). Clinically significant 
abnormalities in laboratory tests 
(serum chemistry, haematology, 
and urinalysis) measurements 
will be reported at Screening 
Visit, Baseline Visit and End of 
Study/Early Withdrawal Visit. 
Physical examination findings 
and body weight measurements 
will be reported at Screening 


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medications/therapies will also be 
recorded throughout the study. 
The following safety endpoints will 
be evaluated: 
• 
Proportion 
of 
subjects 
experiencing at least one AE of any 
grade according to the National 
Cancer 
Institute-Common 
Terminology Criteria for Adverse 
Events (NCI-CTCAE) version 4.03, 
including any serious AEs including 
suspected 
unexpected 
serious 
adverse reactions (SUSARs); all AEs 
will be coded using the Medical 
Dictionary for Regulatory Activities 
(MedDRA) 
system 
organ 
class 
(SOC) and preferred term (PT) (as 
per most recent version) 
Visit, Visit 2 (Day 1) and End of 
Study/Early Withdrawal Visit. 
The 
electrocardiogram 
(ECG) 
findings are to be recorded at the 
Screening Visit and the End of 
Study/Early 
Withdrawal 
Visit. 
Relevant medical history and 
concomitant medications/therapies 
will also be recorded throughout 
the study. 
The following safety endpoints 
will be evaluated: 
• 
Proportion 
of 
subjects 
experiencing at least one AE of 
any grade according to the 
National 
Cancer 
Institute-
Common Terminology Criteria 
for 
Adverse 
Events 
(NCI-
CTCAE) version 5.0, including 
any 
serious 
AEs 
including 
suspected 
unexpected 
serious 
adverse reactions (SUSARs); all 
AEs will be coded using the 
Medical 
Dictionary 
for 
Regulatory Activities (MedDRA) 
system organ class (SOC) and 
preferred term (PT) (as per most 
recent version) 
27 
3.3 
Randomisation and Blinding 
This is an open-label non-randomised 
study. However, independent readers 
will evaluate 68Ga-OPS202 PET/CT 
and 18F-FDG-PET images and will be 
blinded to the acquisition time of the 
PET scan, investigator site and 
clinical status of the subject, including 
pathology, 
laboratory, 
medical 
history and physical exam findings.  
Independent readers are specialised 
radiologists and/or nuclear medicine 
physicians who are experienced in 
reading PET/CT scans. To minimise 
inter- and intra-reader variability in 
results, the readers will be specifically 
trained for this protocol. See the 
Imaging Review Charter (IRC). 
Randomisation and Blinding 
This 
is 
an 
open-label 
non-
randomised study. However, the 
independent readers will evaluate 
68Ga-OPS202 PET/CT and 18F-
FDG-PET/CT images and will be 
blinded to the acquisition time of 
the PET scans and CT scans, 
investigator site and clinical status 
of the subject, including pathology, 
laboratory, medical history and 
physical exam findings.  
The 
independent 
readers 
are 
specialised 
radiologists 
and/or 
nuclear medicine physicians who 
are experienced in reading PET/CT 
scans. To minimise inter- and intra-
reader variability in results, the 
readers will be specifically trained 
for this protocol. Two readers will 


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read 100% of all the images and 
third 
will 
adjudicate 
any 
differences. See the Imaging 
Review Charter (IRC). 
27 
3.4 
Maintenance of Randomisation and 
Blinding 
This is an open-label non-randomised 
study; there is no blinding for the 
imaging product used. The scan 
images collected at Visit 2 and 18F-
FDG-PET images are to be read 
centrally in a blinded manner. 
The images will be sent to a central 
imaging core laboratory (ICL). The 
ICL will ensure that the 68Ga-OPS202 
PET images and CT images are 
initially presented to the readers in a 
blinded manner and randomised to 
temporal sequence. Blinding includes 
subject identification, site, type of 
scanner(s) and acquisition time. Full 
details of this read will be provided in 
the IRC. 
Maintenance of Randomisation 
and Blinding 
All blinding is handled by the 
ICL and described in the IRC. 
28 
3.6 
Study Duration 
Subject participation in the study will 
include: 
• 
Visit 1: a screening period up to 
14 days prior to IIP administration 
• 
Visit 2: a single i.v. injection of a 
fixed 
activity 
range 
of 
68Ga-OPS202 on Day 1 followed 
by PET imaging at 0.5, 1 and 2 
hours ±5 minutes post dosing, and 
a ceCT scan immediately after the 
2-hour PET timepoint 
•      Visit 3: a follow-up visit at Day 14 
(±3 days) for evaluation of safety. 
Study Duration 
Subject participation in the study 
will include: 
• 
Visit 1: a screening period up 
to 14 days prior to IIP 
administration 
• 
Visit 2: a single i.v. injection 
of between 150 MBq to 200 
MBq of 68Ga OPS202 on Day 
1 followed by PET 
acquisition at 0.5, 1 and 2 
hours ±10 minutes post 
dosing.  
•     Visit 3: a follow-up visit at 
Day 14 (±3 days) for 
evaluation of safety. 
• 
Within the study an 
18F-FDG-PET scan and also 
a ceCT scan must also be 
acquired. 
28 
3.7 
Stopping 
Rules 
and 
Discontinuation Criteria 
There are no formal rules for early 
termination of this study. During the 
Stopping 
Rules 
and 
Discontinuation Criteria 
During the conduct of the study, 
SAEs will be reviewed (see 


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conduct of the study, SAEs will be 
reviewed (see Section 8.1.3) as they 
are reported from the study centres to 
identify safety concerns... 
 
Section 8.1.3) as they are reported 
from the study centres to identify 
safety concerns... 
Futility Stopping Rule 
If less than three sstr2 positive 
evaluable subject scans out of 30 
consecutive subjects screened 
with 68Ga-OPS202 PET/CT, or 
less than 8 out of 50, the study 
will be stopped.  
31 
4.3 
Rationale for Inclusion/Exclusion 
Criteria 
Eligibility criteria include those that 
define subjects with breast cancer 
eligible 
for 
imaging 
with 
68Ga-OPS202 PET/CT scan. 
Rationale 
for 
Inclusion/Exclusion Criteria 
Eligibility criteria include those 
that define subjects with breast 
cancer eligible for imaging with 
68Ga-OPS202 PET/CT scan. There 
is no upper limit for age since 
eligibility 
criteria 
exclude 
conditions that could affect 
elderly 
participation 
in 
the 
study. 
32 
5.1 
Table 2 
Visit 2 has only one column (Day 1). 
Physical examination, Haematology, 
Blood chemistry and Urinalysis were 
removed from Day 1 column. 
 
(f) Physical examination: Major 
body systems, body weight, height 
(screening visit only), vital signs 0.5, 
1, 2 and 4 hours post-injection (supine 
and standing systolic and diastolic 
blood pressure, heart rate, body 
temperature, respiratory rate). 
(g)... 
(h)... 
(i) Blood chemistry: urea, creatinine, 
chloride, 
bicarbonate, 
sodium, 
potassium, calcium, phosphate, total 
bilirubin, 
conjugated 
bilirubin, 
alkaline 
phosphatase, 
aspartate 
aminotransferase, 
alanine 
aminotransferase, gamma glutamyl 
transferase, albumin, total protein, 
total cholesterol, triglycerides, fasting 
glucose. 
(J)... 
Visit 2 has additional column for 
Day 2, 
which 
include: 
Concomitant therapies, Vital signs, 
Haematology, Blood chemistry, 
Urinalysis and Adverse events. 
Added physical examination at 
Visit 2 Day 1. 
New row: Contrast enhanced CT 
[m]With 68Ga-OPS202 PET or 
18F-FDG-PET 
 
(f) Physical examination: Major 
body systems, body weight, height 
(screening visit only).  
(g) Vital signs: 0.5, 1, 2 and 4 
hours post-injection (supine and 
standing systolic and diastolic 
blood pressure and heart rate, body 
temperature, respiratory rate). 
(h)... 
(i)... 
(J) 
Blood 
chemistry: 
urea, 
creatinine, creatinine clearance, 
chloride, 
bicarbonate, 
sodium, 
potassium, calcium, phosphate, 


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(k)... 
(l) 68Ga-OPS202 PET/CT imaging: 
PET imaging at 0.5, 1 and 2 hours 
after 
68Ga-OPS202 administration. 
Anonymised images to be sent to the 
Imaging Core Lab. Iodinated i.v. CT 
contrast imaging (chest, abdomen, 
pelvis and brain) after the 2 hour PET 
scan. A low dose CT may be 
performed at the 0.5 and/or 1 hour 
PET (see the Imaging Review Charter 
(IRC)). 
(m) 18F-FDG-PET scan: 18F-FDG-
PET scans, which is part of routine 
clinical diagnosis, will be performed 
during the study period (including the 
Screening period before Day 1), and 
images sent to ICL. A low dose CT 
may 
be 
performed 
with 
the 
18F-FDG-PET 
(see 
the 
Imaging 
Review Charter (IRC)) 
(n)... 
(o)... 
(p) Biopsy: To be performed if not 
already done. Tumour biopsy, which 
is not a prerequisite for inclusion, is 
routinely performed for confirmation 
and staging of the disease, as well as 
classification according to hormone 
receptor status and HER2 status. For 
the study, paraffin embedded slides 
are required for the evaluation of sstr2 
expression by immunohistochemistry 
staining.  
total 
bilirubin, 
conjugated 
bilirubin, alkaline phosphatase, 
aspartate aminotransferase, alanine 
aminotransferase, gamma glutamyl 
transferase, albumin, total protein, 
total 
cholesterol, 
triglycerides, 
fasting glucose. 
(k)... 
(l)... 
(m) 
68Ga-OPS202 
PET/CT 
imaging: PET acquisition at 0.5, 1 
and 2 hours after 68Ga-OPS202 
administration. Iodinated i.v. CT 
contrast imaging (chest, abdomen, 
pelvis 
and 
brain). 
A 
single 
contrast 
enhanced 
computed 
tomography 
(ceCT) 
scan 
is 
required for the study. This can 
be acquired after either of the 
two PET scans (18F-FDG-PET or 
68Ga-OPS202 post the 2-hour 
acquisition). Low-dose CT scans 
will be acquired for the other 
PET scans when the ceCT is not 
obtained (see the Imaging Review 
Charter (IRC)). Anonymised and 
blinded 
to 
acquisition 
time 
images will be sent to the ICL. 
(n) 18F-FDG-PET scan: 18F-FDG-
PET scan, which is part of routine 
clinical 
diagnosis, 
will 
be 
performed during the study period 
and images sent to ICL. A ceCT or 
a low dose CT may be performed 
with the 18F-FDG-PET (see the 
IRC) 
(o)... 
(p)... 
(q) Biopsy: To be performed if not 
already done. Tumour biopsy, 
which is not a prerequisite for 
inclusion, is routinely performed 
for confirmation and staging of the 
disease, as well as classification 
according to hormone receptor 
status and HER2 status. For the 
study, 
an 
archived 
tumour 
sample 
(block 
is 
preferred 
paraffin 
embedded 
slides) 
is 


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required for the evaluation of sstr2 
expression 
by 
immunohistochemistry staining. 
34 
5.2.1 
Procedures 
for 
Screening 
and 
Enrolment (Visit 1) 
... 
• Collection of historical paraffin 
embedded breast tumour slides (if 
available) 
•  18F-FDG-PET (which can also be 
performed at any time during the 
study period, including the Screening 
period). 
Procedures for Screening and 
Enrolment (Visit 1) 
... 
• Collection of historical paraffin 
embedded breast tumour blocks 
or slides with anatomical 
location of the lesion(s) 
indicated 
•  18F-FDG-PET scan (which can 
also be performed at any time 
during the study period, including 
the Screening period). 
34 
5.2.2 
Procedures 
Before 
Study 
IIP 
Administration (Day 1, Visit 2 Pre-
dose) 
The following procedures will be 
performed on Day 1, prior to the IIP 
administration: 
• Eligibility check 
(inclusion/exclusion criteria) 
• Pregnancy test (urine) 
• Concomitant therapies 
• Review of AEs. 
Procedures Before Study IIP 
Administration (Day 1, Visit 2 
Pre-dose) 
The following procedures will be 
performed on Day 1, prior to the 
IIP administration: 
• Eligibility check 
(inclusion/exclusion criteria) 
• Vital signs (body temperature, 
supine and standing blood 
pressure, heart rate and 
respiratory rate) 
• Physical examination 
(including body weight) 
• Pregnancy test (urine) 
• Concomitant therapies 
• Review of AEs. 
34 
5.2.4 
Procedures 
after 
IIP 
Administration (Day 1 and Day 2, 
Visit 2 Post-dose) 
... 
• 
A contrast-enhanced CT scan 
performed after the 2-hour PET 
scan, according to the procedure 
for chest, abdomen, pelvis and 
brain defined in the Imaging 
Manual. 
... 
The following procedures will be 
performed at Visit 2 Day 2: 
Procedures 
after 
IIP 
Administration (Day 1 and Day 
2, Visit 2 Post-dose) 
... 
• 
A single ceCT scan will be 
performed according to the 
site standard procedure for 
chest, abdomen, pelvis and 
brain. This can be acquired 
after either of the two PET 
scans (18F-FDG-PET or 
68Ga-OPS202 post the 2-
hour acquisition). Low-dose 
CT scans will be acquired 


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... 
• 
Physical examination 
with PET scans when 
necessary for attenuation 
correction. See IRC for 
further details. 
35 
5.2.5 
End of Study Visit or Early 
Withdrawal Visit (Day 14±3, Visit 
3) 
... 
•  Physical examination 
End of Study Visit or Early 
Withdrawal Visit (Day 14±3, 
Visit 3) 
... 
•  Physical examination including 
body weight 
35 
6 
IMAGING OF SUBJECTS 
INVESTIGATIONAL 
IMAGING 
PRODUCT 
AND 
DOSING OF SUBJECTS 
36 
6.1.1.1 
 
New subsection 
6.1.1.1 Spillage 
All due precautions and site 
procedures should be implemented 
to prevent spillage or leakage of 
radiodiagnostics. 
Syringes, 
intravenous lines, venous access 
should all be secured and the 
connections thoroughly checked. 
The injection/infusion line should 
be taped in a loop and taped to the 
subject to prevent direct tension 
between the line and the venous 
access. 
Despite precautions, if spillage or 
leakage should occur, then the site 
procedures must be implemented 
to protect the subject, staff and 
members of the public from 
radiation exposure. The subject 
should be moved from the area of 
the spillage or leakage while the 
area is decontaminated. Details of 
the spillage or leakage should be 
recorded 
(including 
how 
the 
incident happened, the time of the 
incident, an estimate (if possible) 
of the amount of substance lost) 
and 
the 
measures 
taken. 
In 
addition, the incident is to be 
reported in the same manner as an 
adverse event using the MedDRA 
PT Product Leakage and as 
appropriate 
PT 
Occupational 


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exposure to radiation (if there is 
exposure to staff) and PT Exposure 
to radiation (if there is exposure to 
the subject or members of the 
public). 
37 
6.1.4 
Investigational Imaging Product 
(68Ga-OPS202) 
... 
•  Radiolabelling of the precursor 
OPS202 achieved by the addition of a 
5 mL sterile hydrochloric acid 
solution of 68Ga, eluted from a sterile 
pharmaceutical 
grade 
68Ge/68Ga 
generator. 
... 
The radioactivity in the syringe is 
measured before and after the 
injection of 
68Ga-OPS202 to the 
subject; 
the 
decay-corrected 
difference 
between 
these 
two 
measurements (in MBq) corresponds 
to the radioactivity dose injected to 
subject.  
Investigational Imaging Product 
(68Ga-OPS202) 
... 
•  Radiolabelling of the precursor 
OPS202 achieved by the addition 
of a 6-mL sterile hydrochloric acid 
solution of 68Ga, eluted from a 
sterile 
pharmaceutical 
grade 
68Ge/68Ga generator. 
... 
The radioactivity in the syringe is 
measured before and after the 
injection of 68Ga-OPS202 to the 
subject; 
the 
decay-corrected 
difference between these two 
measurements 
(in 
MBq) 
corresponds to the radioactivity 
dose injected to subject. 
In 
addition, 
any 
extravasation 
during 
infusion 
should 
be 
measured and this radioactivity 
deducted from the calculated 
amount injected into the subject. 
37 
6.2 
Study Drugs Administered 
At Screening, subjects will be 
allocated a subject number. Following 
confirmation of eligibility for the 
study at Visit 2, subjects will receive 
a single dose of 68Ga-OPS202 (IIP), 
consisting of a peptide mass up to 45 
μg, with a radioactivity range of 150-
200 MBq activity of 68Ga.  
68Ga-OPS202 is prepared, up to 
3 hours prior to administration, by 
68Ga-radiolabelling of an OPS202 
radiolabelling kit containing 50 μg of 
peptide.  
Study Drugs Administered 
68Ga-OPS202 is prepared, up to 
3 hours prior to administration, by 
68Ga-radiolabelling of an OPS202 
radiolabelling kit containing 50 μg 
of peptide. 
38 
7 
ASSESSMENT OF EFFICACY 
For the primary, secondary and 
exploratory endpoints all the sets of 
images obtained at Visit 2 and one 
ASSESSMENT OF EFFICACY 
For the primary, secondary and 
exploratory endpoints all the sets 
of images obtained at Visit 2 and 


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18F-FDG-PET will be sent to an ICL 
for quality control and management 
of the reads. The centralised reads 
will 
be 
undertaken 
by 
two 
independent experienced radiologists 
and/or nuclear medicine physicians, 
and a third for adjudication of 
discordances. The readers will be 
specifically trained for this protocol. 
Full details of the read design and 
conduct will be provided in the IRC. 
For the primary endpoint analysis, the 
number of lesions on each subject 
scan will be counted at each of the 
three timepoints. Scans will be 
blinded to subject identification, site 
and timing post injection. In case of 
discrepancy, images will go to the 
adjudicator (third reader) for a final 
read and adjudication. 
After blinded reading, the readers will 
compare the three scans (the three 
acquisitions 
of 
68Ga-OPS202) 
contemporaneously for each subject 
and note which image(s), if any, 
provides superior images based on 
overall image quality and lesion 
count. 
... 
(1) Review of the three image sets of   
68Ga-OPS202 scans in randomised 
fashion, without and with CT image 
fusion. The ceCT images acquired on 
the same day will be used for 
co-registration  
(2) 
18F-FDG-PET 
images 
for 
standard-of-truth assessments will be 
reviewed by two radiologists not 
involved in 68Ga-OPS202 PET/CT 
images read, and the lesions mapped 
to the 68Ga-OPS202 read. 
... 
(5) 
For 
image 
quality, 
direct 
comparison of the three 68Ga-OPS202 
scans acquired at different times, will 
be conducted for the primary breast 
cancer and then for all other lesions as 
the final step of the blinded read. The 
one 18F-FDG-PET and one ceCT 
scan will be sent to an ICL for 
quality control and management of 
the reads. The centralised reads 
will 
be 
undertaken 
by 
two 
independent 
experienced 
radiologists 
and/or 
nuclear 
medicine physicians, and a third 
for adjudication of discordances 
for most of the reads. The readers 
will be specifically trained for this 
protocol. Full details of the read 
design 
and 
conduct 
will 
be 
provided in the IRC. 
For the primary endpoint analysis, 
the number of lesions and quality 
of the images will be taken into 
consideration by the readers. 
Scans will be blinded to subject 
identification, site and timing post 
injection. No adjudication will be 
conducted 
as 
inter-reader 
differences will be part of the 
evaluation. 
… 
(1) Review of the three image sets 
of 
 
 
68Ga-OPS202 scans in 
randomised fashion, with CT 
image fusion. The ceCT images 
acquired 
will 
be 
used 
for 
co-registration. Two readers will 
read and a third will adjudicate 
any differences. 
(2) 
18F-FDG-PET 
images 
for 
standard-of-truth assessments will 
be reviewed by two radiologists 
not involved in 
68Ga-OPS202 
PET/CT images read, and the 
lesions 
mapped 
to 
the 
68Ga-OPS202 read. Two readers 
will read and a third will 
adjudicate any differences. 
… 
(5) For image quality, direct 
comparison of the three 
68Ga-
OPS202 scans acquired at different 
times, will be conducted for the 
primary breast cancer and then for 


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readers will be allowed to select 
whether one, two or all three 
acquisitions are optimal. The readers 
will be blinded to time point 
sequence. 
(6) The 68Ga-OPS202 PET scans will 
be compared with the 18F-FDG-PET 
scans (with ceCT).  (A ceCT scan will 
be acquired for use with the 
68Ga-OPS202 PET and 18F-FDG-PET 
scan.  This ceCT scan can be acquired 
with either PET scan as long as they 
are 
obtained 
within 
a 
2-week 
timeframe.  A second ceCT scan will 
be acquired if the PET scans are 
greater than 2 weeks apart.  When a 
PET scan is obtained without a ceCT 
scan, a low dose CT scan will be 
obtained for attenuation correction, 
according to site standard practice.) 
... 
(2) The identification of the optimum 
acquisition times based on differences 
in the number of lesions identified at 
each 
scan, 
and 
the 
reader 
interpretation of the optimum image 
in the primary breast lesions.  The 
optimum image acquisition time 
could be one, two or all three 
acquisitions 
i.e. 
.no 
noticeable 
difference between 0.5, 1 and 2 hours 
post infusion. 
all other lesions as the final step of 
the blinded read. The readers will 
be allowed to select whether one, 
two or all three acquisitions are 
optimal. The readers will be 
blinded to time point sequence. No 
adjudication will be required. 
(6) The 68Ga-OPS202 PET scan 
will be compared with the 18F-
FDG-PET scan (with ceCT). 
… 
(2) The identification of the 
optimum acquisition time(s) based 
on differences in the number of 
lesions identified at each scan, and 
the reader interpretation of the 
optimum image in the primary 
breast lesions.  The optimum 
image acquisition time could be 
one, two or all three acquisitions 
timepoints i.e. .no noticeable 
difference between 0.5, 1 and 2 
hours post infusion. 
39 
7 
Key Secondary Endpoint: 
• Differences in the number of 
lesions detected by 68Ga-OPS202 
between the three PET acquisition 
timepoints (0.5, 1 and 2 hours), and 
reader interpretation of optimal 
image(s) in nodular and metastatic 
lesions.   
... 
Other Secondary Endpoints: 
• Comparison to standard-of-truth for 
the primary breast tumour: 
- (68Ga-OPS202 PET/CT) / (18F-
FDG-PET)  
... 
Key Secondary Endpoint: 
• Differences in the number of 
lesions detected by 68Ga-OPS202 
between the three PET acquisition 
timepoints (0.5, 1 and 2 hours), 
and reader interpretation of 
optimal image(s) in nodular and 
metastatic lesions. Significant 
uptake of 68Ga-OPS202 for the 
evaluation of a lesion is an avid 
lesion defined by the blinded 
readers at one of the acquisition 
timepoints as an easily 
identifiable lesion radiologically, 
where there has been clear focal 
uptake of 68Ga-OPS202 and 


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Exploratory Endpoints: 
• Preliminary diagnostic sensitivity 
of 68Ga-OPS202 imaging sstr2 
positive breast cancer tumors by both 
subject based and lesion-based 
analysis compared to standard-of-
truth 
1.5-fold greater uptake than in 
the non-tumoural liver and lung 
parenchyma.  
... 
Other Secondary Endpoints: 
• Comparison to standard-of-truth 
for the primary breast tumour: 
- (68Ga-OPS202 PET/CT) / (18F-
FDG-PET/CT)  
... 
Exploratory Endpoints: 
• Preliminary diagnostic 
sensitivity of 68Ga-OPS202 
imaging sstr2 positive breast 
cancer tumours by both subject 
based and lesion-based analysis 
compared to standard-of-truth 
40 
7 
(c) 
Methods and Timing of 
Assessing, Recording, and 
Analysing Efficacy Data 
... 
• All 68Ga-OPS202 PET/CT scans 
• One 18F-FDG-PET/CT scan. 
•One CeCT scan. 
 
The details of imaging set 
management and read design will be 
fully described in the IRC.  This will 
include the following: 
(c) 
Methods and Timing of 
Assessing, Recording, and 
Analysing Efficacy Data 
... 
• All 68Ga-OPS202 PET/CT scans 
• One 18F-FDG-PET/CT scan. 
•One ceCT scan. 
 
The details of the imaging 
management and read design will 
be fully described in the IRC.  
This will include the following: 
40 
7.1 
Eligible and Evaluable Subjects 
- 
At least two 
68Ga-OPS202 
PET scans that are readable 
(three images are to be 
acquired but 2 of these MUST 
be readable by the central 
readers. If only two PET scans 
are acquired BOTH must be 
readable) with at least one avid 
lesion identified by central 
readers.   
Eligible and Evaluable Subjects 
- 
At least two 68Ga-OPS202 
PET scans that are readable 
(three images are to be 
acquired but 2 of these, 
MUST be readable by the 
central readers; if only two 
PET scans are acquired 
BOTH must be readable) 
with at least one avid lesion 
identified 
by 
central 
readers.   
41 
8.1.1.1 
Intensity Classification 
Adverse events will be recorded and 
graded according to the current 
Intensity Classification 
Adverse events will be recorded 
and graded according to the 


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version of the NCI CTCAE (version 
4.03). 
current version of the 
NCI-CTCAE (version 5.0). 
43-44 
8.1.3 
Any 
SAE 
must 
be 
reported 
immediately (within 24 hours), using 
the email specified at the beginning of 
this protocol, independent of the 
circumstances or suspected cause, if it 
occurs or comes to the attention of the 
investigator at any time during the 
study period. 
 
Any SAE must be reported 
immediately (within 24 hours), to 
Ipsen Pharmacovigilance email 
(preferably) or fax number 
specified at the beginning of this 
protocol, independent of the 
circumstances or suspected cause, 
if it occurs or comes to the 
attention of the investigator at any 
time during the study period. 
45 
8.2 
Clinical Laboratory Tests 
Blood samples will be collected at all 
study visits (Screening Visit [Visit 
1], Baseline/Day 1 [Visit 2], Day 2 
[Visit 2], and End of Study/Early 
Withdrawal [Visit 3]) (see schedule 
of assessment in Table 2) for the 
evaluation of haematology and serum 
chemistry. 
Clinical Laboratory Tests 
Blood samples will be collected at 
all study visits (Screening Visit 
[Visit 1], Day 2 [Visit 2], and End 
of Study/Early Withdrawal [Visit 
3]) (see schedule of assessment in 
Table 2) for the evaluation of 
haematology and serum 
chemistry. 
46 
8.2.2 
Blood Biochemistry 
Blood samples will be collected at all 
visits to assess the following 
parameters: 
• 
urea, creatinine, total 
bilirubin, conjugated bilirubin 
Blood Biochemistry 
Blood samples will be collected at 
all visits to assess the following 
parameters: 
• 
urea, creatinine, 
creatinine clearance, total 
bilirubin, conjugated bilirubin 
46 
8.3 
Physical Examination 
Physical examinations, including 
body weight, will be conducted at 
Screening (Visit 1), IIP 
administration visit (Visit 2 only on 
Day 2), and End of Study (Visit 
3)/Early Withdrawal (see Table 2), 
and height will be measured at 
Screening. 
Physical Examination 
Physical examinations, including 
body weight, will be conducted at 
Screening (Visit 1), IIP 
administration visit (Visit 2 only 
on Day 1), and End of Study 
(Visit 3)/Early Withdrawal (see 
Table 2), and height will be 
measured at Screening. 
51 
11.1 
Analyses Populations 
... 
• 
Sstr2 positive population: All 
subjects who received the dose of 
study 
IIP 
and 
for 
whom 
68Ga-OPS202 
PET/CT 
scan 
images are readable for at least 
one timepoint and one avid lesion 
was identified by central readers. 
Analyses Populations 
... 
• 
Sstr2 positive population: All 
subjects who received the dose 
of study IIP and for whom 
68Ga-OPS202 PET/CT scan 
images are readable for at least 
one timepoint and have one 
avid lesion identified by central 


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• 
Sstr2 positive evaluable 
population: 68Ga-OPS202 sstr2 
positive population with at least 
two evaluable timepoints and 
68Ga-OPS202 timepoints, 18F-
FDG-PET F-FDG-PET scan 
identified by the central readers. 
readers 
18F-FDG-PET/CT 
scan 
and 
a 
ceCT 
scan 
confirmed by the central 
readers 
• 
Sstr2 positive evaluable 
population: 68Ga-OPS202 sstr2 
positive population with at 
least two evaluable 68Ga-
OPS202 timepoints, 18F-
FDG-PET/CT scan and a 
ceCT scan confirmed by the 
central readers. 
49 
11.2 
Sample Size Determination 
It is anticipated that a total of 54 
subjects will be enrolled in the study 
for 68Ga-OPS202 screening, to obtain 
around 16 sstr2 evaluable subjects. 
Considering the estimated prevalence 
of sstr2 overexpression in breast 
cancer, the overall number of 
subjects to be screened with 
68Ga-OPS202 in the study will be 
approximately 54. However, when 
the ICL identifies 16 sstr2 evaluable 
subjects, with eight subjects having 
early disease and eight subjects 
advanced disease, the study will be 
complete. 
This estimation of 16 sstr2 positive 
evaluable subjects is considered 
appropriate for a descriptive analysis 
and it is not based on a formal 
statistical sample size calculation. In 
the event that a subject misses an 
imaging exam and/or measurement 
relevant to the primary and key 
secondary endpoints, an additional 
subject will be recruited as a 
replacement to ensure an adequate 
sample size in the sstr2 positive 
evaluable set.  
Sample Size Determination 
It is anticipated that a total of 
approximately 54 subjects will be 
enrolled 
in 
the 
study 
for 
68Ga-OPS202 PET/CT imaging, 
to obtain around 16 sstr2 positive 
BC 
evaluable 
subjects. 
Considering 
the 
estimated 
prevalence of sstr2 overexpression 
in breast cancer, the overall 
number 
of 
subjects 
to 
be 
administered 68Ga-OPS202 in the 
study will be over 50. However, 
when the ICL identifies 16 sstr2 
positive evaluable subjects, with a 
minimum of two subjects with 
advanced disease, the study will be 
complete. 
This estimation of 16 sstr2 
positive BC evaluable subjects is 
considered appropriate for a 
descriptive analysis and it is not 
based on a formal statistical 
sample size calculation. In the 
event that a subject misses an 
imaging exam and/or 
measurement relevant to the 
primary and key secondary 
endpoints, an additional subject 
will be recruited as a replacement 
to ensure an adequate sample size 
in the sstr2 positive BC evaluable 
set. 
50-51 
11.4.4 
Efficacy Evaluation 
Key Secondary Endpoint: 
Efficacy Evaluation 
Key Secondary Endpoint: 


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• 
Differences in the number of 
lesions detected by 68Ga-OPS202 
between the three PET acquisition 
timepoints (0.5, 1 and 2 hours) and 
reader interpretation of optimal 
image(s) in nodular and metastatic 
lesions. 
• 
Differences at each of the 
three timepoints in SUVmean and 
SUVmax, as measured by the tumour-
to-background ratio in the primary 
tumour and each of the major 
anatomic sites (liver, lymph nodes, 
bone, lungs and brain). 
Other Secondary Endpoints: 
•  Differences in relative lesion 
counts as a ratio of the number of 
lesions detected by 68Ga-OPS202 at 
0.5, 1 and 2 hours post dose 
respectively, compared to the number 
of lesions assessed by standard-of-
truth (descriptive analyses). The 
standard-of-truth is the 18F-FDG PET 
scan images acquired at any time 
during the study period (including 
the Screening period)... 
• 
• Differences in the number 
of lesions detected by 68Ga-
OPS202 between the three 
PET acquisition timepoints 
(0.5, 1 and 2 hours) and 
reader 
interpretation 
of 
optimal image(s) in nodular 
and 
metastatic 
lesions. 
Significant 
uptake 
of 
68Ga-OPS202 
for 
the 
evaluation of a lesion is an 
avid lesion defined by the 
blinded readers at one of 
the acquisition timepoints 
as an easily identifiable 
lesion 
radiologically, 
where there has been clear 
focal 
uptake 
of 
68Ga-OPS202 and 1.5-fold 
or greater uptake than in 
the non-tumoural liver 
and lung parenchyma. 
• 
The SUVmean and SUVmax 
in the primary lesion 
between each of the three 
timepoints, measured in 
the most avid lesions 
(using the 
68Ga-OPS202 
scans).  This is assessed by 
the 
tumour-to-
background ratio in the 
primary tumour and each 
of the major anatomic 
sites (liver, lymph nodes, 
bone, lungs and brain); 
the background consists 
of 
non-tumoural 
liver 
parenchyma 
or 
aortic 
blood 
where 
sufficient 
liver is not available. 
Identification of lesions to 
be used will be made by 
one of the two primary 
readers.  
Other Secondary Endpoints: 
•  Differences in relative lesion 
counts as a ratio of the number of 
lesions detected by 
68Ga-OPS202/ceCT at 0.5, 1 and 2 


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hours post dose respectively, 
compared to the number of lesions 
assessed by standard-of-truth 
(descriptive analyses). The 
standard-of-truth is the 18F-
FDG-PET/CT scan images 
acquired at any time during the 
study period (including the 
Screening period)… 
51 
11.4.6 
Safety Evaluation 
All AEs will be coded according to 
the MedDRA version (latest version 
in use) and will be classified by 
MedDRA SOC and PT. AEs, SAEs, 
AEs leading to discontinuation of 
study treatment, and AEs leading to 
death will be summarised and listed 
by subject, SOC class and PT. 
Adverse events reported by 
investigators using the NCI-CTCAE 
classification (version 4.03) will be 
coded using MedDRA dictionary 
(latest available version). 
Safety Evaluation 
All AEs will be coded according 
to the MedDRA version (latest 
version in use) and will be 
classified by MedDRA SOC and 
PT. AEs, SAEs, AEs leading to 
discontinuation of study treatment, 
and AEs leading to death will be 
summarised and listed by subject, 
SOC class and PT. Adverse events 
reported by investigators using the 
NCI-CTCAE classification 
(version 5.0) will be coded using 
MedDRA dictionary (latest 
available version). 


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SUMMARY & OUTCOME OF CHANGES: 
STUDY NUMBER 
D-FR-01070-003 
AMENDED PROTOCOL 
VERSION NUMBER & 
DATE 
 
Version 2.0, Amendment 1.0; 27 June 2018 
 
SUBSTANTIAL  
 
NON-SUBSTANTIAL  
 
 
REASONS FOR CHANGES 
 
The protocol was amended to modify the restrictions on the 
minimum number of subjects per tumour stage, to update the 
version of the NCI CTCAE version to be used, to update 
pharmacovigilance contact details, to add instructions on 
spillage of the product, to make clarifications and to correct 
typographical errors. 
OTHER ACTION REQUIRED? 
CRF UPDATE  
 
Yes 
 
  
No 
 
 
 
(tick one) 
 
LOCAL CONSENT FORM UPDATE  
Yes 
 
  
No 
 
 
 
(tick one) 
 
DATABASE UPDATE  
Yes 
 
  
No 
 
 
 
(tick one) 
 
REPORTING & ANALYSIS PLAN 
(RAP) UPDATE 
Yes 
 
  
No 
 
 
 
(tick one) 
 
 


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Appendix 2 Protocol Summary of Changes - Amendment 2.0 


IPSEN GROUP 
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STUDY NUMBER 
D-FR-01070-003 
PROTOCOL TITLE: 
A non-randomised phase II study to evaluate the 
optimal uptake time of 68Ga-OPS202 as a sstr2 
positive PET imaging agent in subjects with newly 
diagnosed breast cancer 
AMENDED PROTOCOL VERSION 
NUMBER & DATE 
Version 3.0, Amendment 2.0; 14 September 2018 
THE FOLLOWING AMENDMENTS ARE PROPOSED: 
Version Date 
27 JUNE 2018 
14 SEPTEMBER 2018 
Page  
Section 
WAS 
IS 
 
 
 
 
1 
Title page Version 2.0, Amendment 1.0; 
27 June 2018 
Version 3.0, Amendment 2.0; 14 
September 2018 
8 
Synopsis 
Exclusion criteria: 
... 
15. 
Subject who experienced a 
previous cancer (except basocellular 
carcinoma of the skin and/or in situ 
carcinoma of the cervix/uterus), 
and/or subjects treated with curative 
intent and free from disease for more 
than 5 years. 
Exclusion criteria: 
... 
15. 
Subject who experienced 
a previous cancer (except 
basocellular carcinoma of the skin 
and/or in situ carcinoma of the 
cervix/uterus, and/or subjects 
treated with curative intent and 
free from disease for more than 5 
years). 
31 
4.2 
Exclusion Criteria 
... 
(15) 
Subject who experienced a 
previous cancer (except basocellular 
carcinoma of the skin and/or in situ 
carcinoma of the cervix/uterus), 
and/or subjects treated with curative 
intent and free from disease for more 
than 5 years. 
Exclusion Criteria 
... 
(15) 
Subject who experienced 
a previous cancer (except 
basocellular carcinoma of the skin 
and/or in situ carcinoma of the 
cervix/uterus, and/or subjects 
treated with curative intent and 
free from disease for more than 5 
years). 


IPSEN GROUP 
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PAGE 95/102 
 
 
SUMMARY & OUTCOME OF CHANGES: 
STUDY NUMBER 
D-FR-01070-003 
AMENDED PROTOCOL 
VERSION NUMBER & 
DATE 
 
Version 3.0, Amendment 2.0; 14 September 2018 
 
SUBSTANTIAL  
 
NON-SUBSTANTIAL  
 
 
REASONS FOR CHANGES 
 
The protocol was amended to correct a typo in exclusion 
criterion 15, which defines previous cancer of subjects not 
eligible for the study. 
OTHER ACTION REQUIRED? 
CRF UPDATE  
 
Yes 
 
  
No 
 
 
 
(tick one) 
 
LOCAL CONSENT FORM UPDATE  
Yes 
 
  
No 
 
 
 
(tick one) 
 
DATABASE UPDATE  
Yes 
 
  
No 
 
 
 
(tick one) 
 
REPORTING & ANALYSIS PLAN 
(RAP) UPDATE 
Yes 
 
  
No 
 
 
 
(tick one) 
 


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Appendix 3 Protocol Summary of Changes - Amendment 3.0 


IPSEN GROUP 
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PAGE 97/102 
 
 
STUDY NUMBER 
D-FR-01070-003 
PROTOCOL TITLE: 
A non-randomised phase II study to evaluate the 
optimal uptake time of 68Ga-OPS202 as a sstr2 
positive PET imaging agent in subjects with newly 
diagnosed breast cancer 
AMENDED PROTOCOL VERSION 
NUMBER & DATE 
Version 4.0, Amendment 3.0; 20 May 2019 
THE FOLLOWING AMENDMENTS ARE PROPOSED: 
Version Date 
14 SEPTEMBER 2018 
20 MAY 2019 
Page  
Section 
WAS 
IS 
1 
Title page 
Version 3.0, Amendment 2.0; 14 
September 2018 
Version 4.0, Amendment 3.0; 20 
May 2019 
1 
Title page 
Sponsor Signatory:  
 
 
Ipsen Innovation 
 
Global Drug Development 
 
ZI de Courtaboeuf 5, Avenue du 
Canada 
91940 Les Ulis, France  
Tel:  
 
(mobile: 
 
 
Fax:  
 
Sponsor’s Medically 
Responsible Person:  
 
 
Ipsen Pharma 
Global Drug Development 
65 quai Georges Gorse  
92100 Boulogne-Billancourt 
France  
Mobile: 
 
2 
INVESTIGATOR’S 
AGREEMENT 
Sponsor's 
Representative 
Signature: 
NAME: 
 
TITLE: 
 
SIGNATURE: 
 
DATE: 
OFFICE: Ipsen Innovation 
Global Drug Development 
Z.I. de Courtaboeuf 
5 avenue du Canada 
91940 Les Ulis 
France 
Sponsor's 
Representative 
Signature: 
NAME: 
 
 
TITLE: 
 
 
 
 
 
Ipsen 
Biopharm Ltd SIGNATURE: 
    
DATE: 
OFFICE:  Ipsen Biopharm Ltd  
102 Park Drive 
Milton Park 
 
Abingdon, OX14 4RY  
United Kingdom 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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4 
SUMMARY OF 
CHANGES 
 
New Section: 
SUMMARY OF CHANGES 
The current version of the 
protocol was released on 20 May 
2019 and includes Amendment 
3. For all protocol amendments, 
amendment 
forms 
were 
prepared and are provided in 
the Appendices listed in Table 1. 
All modifications (except minor 
changes) are presented in the 
appendices. 
Table 1 List 
of 
Protocol 
Amendments 
Amendment 
Release 
date
 
Amendment form 
1 
27 
June 
2018
 
Appendix 1 
 
2 
14 
September 
2018
 
Appendix 2 
 
3 
20 
May 
2019
 
Appendix 3 
5 
Synopsis 
Name of finished product: 
68Ga-OPS202 
solution 
for 
injection.   
Name of active ingredient(s): 
68Ga-OPS202 
 
Planned study period: 
FPI: July 2018 - LPO: 
December 2018 
Name 
of 
finished 
product: 
68Ga-OPS202 - 68Ga-satoreotide 
trizoxetan 
Name of active ingredient(s): 
68Ga-OPS202 - INN for OPS202 
is satoreotide trizoxetan 
 
Planned study period: 
FPI: July 2018 - LPO: December 
2018 
19 
LIST OF 
ABBREVIATIONS 
 
Added: 
INN 
International 
nonproprietary name 
21 
1.2 
Name 
and 
Description 
of 
Investigational 
Imaging 
Product 
OPS202 is a new generation 
somatostatin 
analogue 
(antagonist) 
compound 
with 
potential 
superior 
tumour 
detection 
Name 
and 
Description 
of 
Investigational Imaging Product 
OPS202 (satoreotide trizoxetan) 
is a new generation somatostatin 
analogue (antagonist) compound 
with potential superior tumour 
detection 


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23 
1.6 
Population to Be Studied 
Several types of tumours other 
than NETs express sstr2 making 
the imaging of these tumours 
with 
peptide 
receptor 
radionuclide 
such 
as 
68Ga-OPS202 possible. This 
study will enrol adult female 
subjects with newly diagnosed 
early or locally advanced breast 
cancer to detect those expressing 
sstr2. 
Population to Be Studied 
Several types of tumours other 
than NETs express sstr2 making 
the imaging of these tumours with 
peptide receptor radionuclide such 
as 68Ga-OPS202 possible. This 
study will enrol adult female 
subjects with newly diagnosed 
early or advanced breast cancer to 
detect those expressing sstr2. 
25 
3.1 
General Design and Study 
Schema 
... 
Subjects may be hospitalised 
overnight upon completion of the 
68Ga-OPS202 PET/CT scans at 
the discretion of the investigator. 
All subjects (either hospitalised 
or not) will attend a consultation 
on Day 2 for a physical 
examination, vital signs and 
laboratory tests. 
General 
Design 
and 
Study 
Schema 
... 
Subjects may be hospitalised 
overnight upon completion of the 
68Ga-OPS202 PET/CT scans at 
the discretion of the investigator. 
All subjects (either hospitalised or 
not) will attend a consultation on 
Day 2 for vital signs and laboratory 
tests. 
27 
3.2.4 
Safety 
Endpoints 
and 
Evaluations 
The investigator will report the 
occurrence of any AE throughout 
the 
study 
and 
vital 
signs 
(including blood pressure and 
heart rate) measurements at each 
visit: Screening Visit (Visit 1; 
Day -14 to -1), Visit 2 (Day 1), 
Baseline Visit (Visit 2; Day 2) 
and 
End 
of 
Study/Early 
Withdrawal Visit 
(Visit 
3). 
Clinically 
significant 
abnormalities in laboratory tests 
(serum chemistry, haematology, 
and urinalysis) measurements 
will be reported at Screening 
Visit, Baseline Visit and End of 
Study/Early Withdrawal Visit. 
Safety 
Endpoints 
and 
Evaluations 
The investigator will report the 
occurrence of any AE throughout 
the study and vital signs 
(including blood pressure and 
heart rate) measurements at each 
visit: Screening Visit (Visit 1; Day 
-14 to -1), Visit 2 (Day 1), Visit 2 
(Day 2) and End of Study/Early 
Withdrawal Visit (Visit 3). 
Clinically significant 
abnormalities in laboratory tests 
(serum chemistry, haematology, 
and urinalysis) measurements will 
be reported at Screening Visit, 
Visit 2 (Day 2) and End of 
Study/Early Withdrawal Visit. 
29 
3.5 
Study Imaging Product and 
Dosage 
... 
Study Imaging Product and 
Dosage 
... 


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The radiolabelling kit will be 
packaged by Beaufour Ipsen 
Industrie, 20 rue Ethe Virton 
28100 
Dreux, 
France 
and 
delivered in a sufficient quantity 
to the investigational sites with a 
delivery 
note 
including 
an 
acknowledgement of receipt. 
The radiolabelling kit will be 
packaged and delivered in a 
sufficient quantity to the 
investigational sites with a 
delivery note including an 
acknowledgement of receipt. 
33 
5.1 
Study Schedule 
Footnotes: 
(a) 
Study visits: Screening 
Visit up to 14 days before IIP 
administration; Subjects may be 
hospitalised overnight at the 
discretion of the investigator at 
Visit 2. All subjects (either 
hospitalised or not) will attend 
consultation on Day 2, which is 
part of Visit 2, for: review of 
AEs, 
new 
or 
changed 
concomitant medications, vital 
signs, 
physical 
examination, 
haematology, 
biochemistry, 
urinalysis. 
... 
(g) 
Vital signs: 0.5, 1, 2 and 
4 hours post-injection (supine 
and 
standing 
systolic 
and 
diastolic blood pressure and heart 
rate, 
body 
temperature, 
respiratory rate). 
... 
(i)  
Haematology: 
Red 
blood 
cell 
(RBC) 
count, 
haemoglobin, haematocrit, mean 
corpuscular 
volume 
(MCV), 
mean corpuscular haemoglobin 
(MCH), 
mean 
corpuscular 
haemoglobin 
concentration 
(MCHC), 
white 
blood 
cell 
(WBC) count with differential 
(neutrophils, 
lymphocytes, 
monocytes, 
eosinophils, 
basophils, 
and 
others) 
and 
platelet count. 
Study Schedule 
Footnotes: 
(a) 
Study visits: Screening 
Visit up to 14 days before IIP 
administration; Subjects may be 
hospitalised 
overnight 
at 
the 
discretion of the investigator at 
Visit 2. All subjects (either 
hospitalised or not) will attend 
consultation on Day 2, which is 
part of Visit 2, for: review of AEs, 
new or changed concomitant 
medications, 
vital 
signs, 
haematology, 
biochemistry, 
urinalysis. 
... 
(g) 
Vital signs: pre-dose and 
at 0.5, 1, 2 and 4 hours post-
injection (supine and standing 
systolic 
and 
diastolic 
blood 
pressure and heart rate, body 
temperature, respiratory rate). 
... 
(i)  
Haematology: Red blood 
cell (RBC) count, haemoglobin, 
haematocrit, mean corpuscular 
volume (MCV), mean corpuscular 
haemoglobin 
(MCH), 
mean 
corpuscular 
haemoglobin 
concentration 
(MCHC), 
white 
blood cell (WBC) count with 
differential 
(neutrophils, 
lymphocytes, 
monocytes, 
eosinophils, 
basophils) 
and 
platelet count. 
38 
6.3 
Concomitant 
Medication/ 
Therapy 
Concomitant 
Medication/ 
Therapy 


IPSEN GROUP 
D-FR-01070-003 
 
CONFIDENTIAL 
 
PROTOCOL VERSION 4.0: 20 MAY 2019 
PAGE 101/102 
 
 
Version Date 
14 SEPTEMBER 2018 
20 MAY 2019 
Page  
Section 
WAS 
IS 
... 
The following concomitant 
medications /therapies are not 
permitted during this study up to 
48 hours post PET/CT scan: 
• 
Administration of a 
radiopharmaceutical within 8 
half-lives of its radionuclide 
... 
The 
following 
concomitant 
medications /therapies are not 
permitted during this study up to 
48 hours post PET/CT scan: 
• 
Administration of any 
radiopharmaceutical 
38 
6.4 
Procedures 
for 
Monitoring 
Subject Compliance 
...The injected peptide mass dose 
and radioactivity dose will be 
recorded in the medical file and 
in the eCRF for each subject. 
Procedures 
for 
Monitoring 
Subject Compliance 
...The injected peptide mass dose 
and radioactivity dose (calculated 
from the IIP volume) will be 
recorded in the medical file and in 
the eCRF for each subject. 
43 
8.1.1.4 
Laboratory Test Abnormalities 
... 
• 
They are considered as 
clinically significant by the 
investigator. 
Laboratory Test Abnormalities 
... 
• 
They are considered as 
clinically significant by the 
investigator, or the laboratory 
test abnormality suggests a 
disease and/or organ toxicity 
that is new or has worsened 
from baseline based on sponsor 
review. 
46 
8.2.1 
Haematology 
... white blood cell (WBC) 
absolute 
count 
(neutrophils, 
lymphocytes, 
monocytes, 
eosinophils, 
basophils, 
and 
others) and platelet count. 
Haematology 
... 
white blood cell (WBC) 
absolute 
count 
(neutrophils, 
lymphocytes, 
monocytes, 
eosinophils, 
basophils) 
and 
platelet count. 
47 
8.4 
Vital Signs 
Blood pressure and heart rate 
will be assessed at Screening 
(Visit 1), IIP administration visit 
(Visit 2 Day 1 at 0.5, 1, 2, 4 hours 
post-injection and on Day 2)... 
Vital Signs 
Blood pressure and heart rate will 
be assessed at Screening (Visit 1), 
IIP administration visit (Visit 2: 
Day 1 pre-dose and at 0.5, 1, 2, 4 
hours post-injection and on Day 
2)... 


IPSEN GROUP 
D-FR-01070-003 
 
CONFIDENTIAL 
 
PROTOCOL VERSION 4.0: 20 MAY 2019 
PAGE 102/102 
 
 
SUMMARY & OUTCOME OF CHANGES: 
STUDY NUMBER 
D-FR-01070-003 
AMENDED PROTOCOL 
VERSION NUMBER & 
DATE 
 
Version 4.0, Amendment 3.0; 20 May 2019 
SUBSTANTIAL  
 
NON-SUBSTANTIAL  
 
 
REASONS FOR CHANGES 
 
The protocol was amended to update personnel (Sponsor’s 
representative and medically responsible person), to amend 
concomitant medications that are not allowed and conditions in 
which abnormalities in laboratory test values should be reported as 
AEs, to make minor corrections and clarifications. 
OTHER ACTION REQUIRED? 
CRF UPDATE  
 
Yes 
 
  
No 
 
 
 
(tick one) 
 
LOCAL CONSENT FORM UPDATE  
Yes 
 
  
No 
 
 
 
(tick one) 
 
DATABASE UPDATE  
Yes 
 
  
No 
 
 
 
(tick one) 
 
REPORTING & ANALYSIS PLAN 
(RAP) UPDATE 
Yes 
 
  
No 
 
 
 
(tick one) 
 
 
 

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IPSEN GROUP 
D-FR-01070-003
CONFIDENTIAL 
SAP Final Version 2.0: 10 january 2020
Page 1 of 39
STATISTICAL AND ANALYSIS PLAN 
PROTOCOL TITLE A NON-RANDOMISED PHASE II STUDY TO EVALUATE THE 
OPTIMAL UPTAKE TIME OF 68GA-OPS202 AS A SSTR2 POSITIVE PET IMAGING 
AGENT IN SUBJECTS WITH NEWLY DIAGNOSED BREAST CANCER 
PROTOCOL VERSION AND DATE: 3.0 – 14 SEPTEMBER 2018
SAP Version
Date
Final Version 1.0
30 August 2018
Final Version 2.0
10 January 2020


IPSEN GROUP 
D-FR-01070-003
CONFIDENTIAL 
SAP Final Version 2.0: 10 january 2020
Page 2 of 39
STUDY NUMBER:
D-FR-01070-003
EUDRACT NUMBER
2018-000028-33
PROTOCOL TITLE:
A non-randomised, phase II study to evaluate the 
optimal uptake time of 68Ga-OPS202 as a sstr2 positive 
PET imaging agent in subjects with newly diagnosed 
breast cancer.
SAP VERSION:
Final Version 2.0
SAP DATE:
10 January 2020
Further to your review and agreement to the Statistical and Analysis Plan version 
indicated above, please sign to indicate approval for your area of responsibility: 
RESPONSIBILITY
NAME, TITLE & OFFICE
SIGNATURE
DATE
Clinical 
Statistics 
Manager or designee
 Biostatistics 
Oncology
Ipsen Bioscience, Cambridge, 
Massachusetts, U.S.
Medical Development 
Director
Ipsen Pharma
65 quai Georges Gorse
92100 Boulogne-Billancourt
France
RESPONSIBILITY
NAME, TITLE & OFFICE
SIGNATURE
DATE
Study statistician
Covance Clinical Development 
SARL
Manager statistician
 Biostatistics
Covance Clinical Development 
SARL
IMPORTANT: This completed record (with additional sheets, where required), confirms 
the above-mentioned Statistical and Analysis Plan version became the Final Statistical and 
Analysis Plan
PPD
PPD
PPD
PPD
PPD
PPD
PPD


IPSEN GROUP 
D-FR-01070-003
CONFIDENTIAL 
SAP Final Version 2.0: 10 january 2020
Page 3 of 39
History of Changes
Old Version 
Number
Date Old 
Version
Date New 
Version
Primary Reason for Change
Page
Section
Was
Is
30 Aug 
2018
10 Jan 2020
-
Update in approval page
-
CRO name: Removal of
-
Statement of decision of study
premature termination
-
Section 3.2: Deletion of planned
analyses and/or outputs.
CCI


IPSEN GROUP 
D-FR-01070-003
CONFIDENTIAL 
SAP Final Version 2.0: 10 january 2020
Page 4 of 39
TABLE OF CONTENTS 
1 
INFORMATION TAKEN FROM THE PROTOCOL ............................................... 9 
1.1 
Study objectives ............................................................................................................... 9 
1.1.1 
Primary objective ........................................................................................... 9 
1.1.2 
Secondary objectives ..................................................................................... 9 
1.1.3 
Exploratory objectives ................................................................................... 9 
1.2 
Study design ..................................................................................................................... 9 
1.2.1 
Study population ......................................................................................... 10 
1.2.2 
Study exposure ............................................................................................ 10 
1.3 
Methods and procedures .............................................................................................. 11 
1.3.1 
Subject identification and allocation to study treatment ........................... 11 
1.3.2 
Subjects assessments ................................................................................... 11 
1.3.2.1 
Efficacy assessments .................................................................................... 11 
1.3.2.2 
Safety assessments ....................................................................................... 13 
1.3.2.3 
Other assessments ........................................................................................ 15 
1.3.2.4 
Withdrawal/discontinuation ......................................................................... 15 
1.3.3 
Schedule of assessments ............................................................................. 16 
1.3.4 
Planned sample size .................................................................................... 17 
2 
SUBJECT POPULATIONS (ANALYSIS SETS) ...................................................... 17 
2.1 
Efficacy populations ..................................................................................................... 19 
2.1.1 
68Ga-OPS202 screened population ............................................................. 19 
2.1.2 
Sstr2 positive population ............................................................................. 19 
2.1.3 
Sstr2 positive evaluable population............................................................ 19 
2.2 
Safety population .......................................................................................................... 19 
2.3 
Primary population ....................................................................................................... 20 
3 
STATISTICAL METHODS ........................................................................................ 20 
3.1 
Statistical analysis strategy .......................................................................................... 20 
3.1.1 
Primary efficacy endpoints ......................................................................... 20 
3.1.2 
Secondary efficacy endpoints ..................................................................... 21 
3.1.3 
Safety endpoints .......................................................................................... 22 
3.1.4 
Multiplicity .................................................................................................. 22 
3.1.5 
Significance testing and estimation ............................................................ 22 
3.2 
Analysis methods ........................................................................................................... 22 
3.2.1 
Efficacy ........................................................................................................ 22 
3.2.1.1 
Primary efficacy analysis ............................................................................. 23 
3.2.1.2 
Secondary efficacy analysis ......................................................................... 24 
3.2.2 
Safety ........................................................................................................... 29 
3.2.2.1 
Adverse events .............................................................................................. 29 


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CONFIDENTIAL 
SAP Final Version 2.0: 10 january 2020
Page 5 of 39
3.2.2.2 
Laboratory data ........................................................................................... 30 
3.2.2.3 
Vital signs ..................................................................................................... 31 
3.2.2.4 
ECG .............................................................................................................. 31 
3.2.2.5 
Physical examination ................................................................................... 31 
3.2.3 
Missing data and outliers ............................................................................ 32 
3.2.3.1 
Missing data ................................................................................................. 32 
3.2.3.2 
Missing or incomplete dates ........................................................................ 32 
3.2.3.3 
Outliers ........................................................................................................ 33 
3.2.4 
Subject disposition ....................................................................................... 33 
3.2.5 
Withdrawals ................................................................................................. 33 
3.2.6 
Demographic and baseline characteristics ................................................ 33 
3.2.7 
Medical and surgical history ...................................................................... 34 
3.2.8 
Subject compliance ..................................................................................... 35 
3.2.8.1 
Subject exposure to IIP ................................................................................ 35 
3.2.8.2 
Protocol deviations ...................................................................................... 35 
3.2.9 
Prior and concomitant therapies ................................................................ 35 
3.2.9.1 
Prior and concomitant medications ............................................................. 36 
3.2.9.2 
Prior and concomitant non-drug therapies ................................................. 36 
3.2.9.3 
Concomitant medications for breast cancer ................................................ 36 
3.2.9.4 
Concomitant surgical procedures ................................................................ 37 
3.2.10 
Derived data ................................................................................................. 37 
3.2.11 
Rules and data formats ............................................................................... 37 
3.2.12 
Pooling of Centres ....................................................................................... 38 
3.2.13 
Interim analysis ........................................................................................... 38 
3.2.14 
Covariates and analysis of subgroups ........................................................ 38 
4 
COMPUTER SYSTEMS, SOFTWARE AND VALIDATION OF PROGRAMS . 38 
4.1 
Hardware ....................................................................................................................... 38 
4.2 
Software ......................................................................................................................... 38 
4.3 
Validation programs ..................................................................................................... 38 
4.4 
Restitution of the programs ......................................................................................... 38 
5 
CHANGES FROM PROTOCOL ................................................................................ 39 
6 
REFERENCES .............................................................................................................. 39 
7 
DATA PRESENTATION ............................................................................................. 39 


IPSEN GROUP 
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CONFIDENTIAL 
SAP Final Version 2.0: 10 january 2020
Page 6 of 39
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS
•
ßHCG
Beta human chorionic gonadotropin
•
AE:
Adverse Event
•
ALT:
Alanine aminotransferase
•
AP:
Alkaline phosphatase
•
AST:
Aspartate aminotransferase
•
ATC:
Anatomical Therapeutic Chemical
•
BC:
Breast cancer
•
BMI:
Body mass index
•
BUN:
Blood urea nitrogen
•
ceCT
Contrast enhanced CT
•
CI:
Confidence Interval
•
CRO:
Contract research organisation
•
CT:
Computed tomography
•
D:
Day
•
e:
Electronic
•
ECG:
Electrocardiogram
•
ECOG:
Eastern Cooperative Oncology Group
•
eCRF:
Electronic case report form
•
EDC:
Electronic data capture
•
EOS:
End Of Study
•
EW:
Early Withdrawal
•
18F-FDG:
18F-fluorodeoxyglucose
•
68Ga:
Gallium - 68
•
GCP:
Good Clinical Practice
•
GGT:
Gamma-Glutamyl Transferase
•
HCG:
Human chorionic gonadotropin
•
i.v.:
Intravenous
•
ICH:
International Conference on Harmonisation
•
ICL:
Imaging core laboratory
•
IIP:
Investigational Imaging Product
•
IRC:
Imaging review charter


IPSEN GROUP 
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CONFIDENTIAL  
 
SAP Final Version 2.0: 10 january 2020 
 
Page 7 of 39 
 
 
 
• 
LLN: 
Lower limit of normal range 
• 
max: 
Maximum 
• 
MBq: 
Megabecquerel 
• 
MCH: 
Mean corpuscular haemoglobin 
• 
MCHC: 
Mean corpuscular haemoglobin concentration 
• 
MCV: 
Mean corpuscular volume 
• 
MedDRA: 
Medical Dictionary for Regulatory Activities 
• 
min: 
Minimum 
• 
NCI-CTCAE: 
National Cancer Institute - Common Terminology 
Criteria for Adverse Events 
• 
PET: 
Positron emission tomography 
• 
PT: 
Preferred Term 
• 
QC: 
Quality control 
• 
QRS: 
QRS interval duration 
• 
QT: 
Time interval for ventricular depolarisation and 
repolarisation 
• 
QTc: 
Corrected QT interval 
• 
RBC: 
Red blood cell 
• 
SAE: 
Serious Adverse Event 
• 
SAP: 
Statistical and Analysis Plan 
• 
SAS®: 
Statistical Analysis System® 
• 
SD: 
Standard deviation 
• 
SI: 
Standard International 
• 
SNR: 
Signal-to-noise ratio 
• 
SOC: 
System organ class 
• 
SOP: 
Standard Operating Procedure 
• 
SOT: 
Standard-of-truth 
• 
SSA: 
Somatostatin analogues 
• 
sstr: 
Somatostatin receptors 
• 
sstr2: 
Somatostatin receptor subtype 2 
• 
SUSAR: 
Suspected unexpected serious adverse reaction 
• 
SUV: 
Standardised uptake value 
• 
SUVmax: 
Maximum standardized uptake value 


IPSEN GROUP 
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CONFIDENTIAL  
 
SAP Final Version 2.0: 10 january 2020 
 
Page 8 of 39 
 
 
 
• 
SUVmean: 
Mean standardized uptake value 
• 
TEAE: 
Treatment Emergent Adverse Event 
• 
TFLs: 
Tables, Figures and Listings 
• 
TNM: 
Tumour, node and metastasis 
• 
ULN: 
Upper limit of normal range 
• 
V: 
Volume of distribution 
• 
VOI: 
Volume of interest 
• 
WBC: 
White blood cell 
• 
WHO: 
World Health Organization 
• 
WHO-DD: 
World Health Organization (WHO) Drug Dictionary 


IPSEN GROUP 
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CONFIDENTIAL  
 
SAP Final Version 2.0: 10 january 2020 
 
Page 9 of 39 
 
 
 
1 
INFORMATION TAKEN FROM THE PROTOCOL  
1.1 
Study objectives 
1.1.1 
Primary objective 
The co-primary objectives of the study are to evaluate the percentage of women with newly 
diagnosed breast cancer who have somatostatin receptor 2 (sstr2) positive lesions that are 
identified using 68Ga-OPS202 and to define the optimal positron emission tomography (PET) 
imaging time of 68Ga-OPS202 at 0.5, 1.0 and 2 hours post injection, based on detected lesions 
in adult women with sstr2 positive newly diagnosed early or advanced breast cancer. 
1.1.2 
Secondary objectives 
The secondary objectives of the study are as follows: 
• 
To further define the optimal uptake time of 68Ga-OPS202 based on quantitative 
maximum standardised uptake value (SUVmax) and other quality parameters 
• 
To describe the safety and tolerability of 68Ga-OPS202 in women with newly diagnosed 
(early or advanced) sstr2 positive breast cancer.  
1.1.3 
Exploratory objectives 
The exploratory objectives of the study include the following: 
• 
To provide preliminary estimates of the sensitivity of 68Ga-OPS202 PET/computed 
tomography (CT) scan imaging, as well as SUV ratio and signal-to-noise ratios (SNR) 
• 
To assess the correlation in terms of number of avid lesions between 18F-
fluorodeoxyglucose (18F-FDG)-PET and 68Ga-OPS202 
• 
To assess the correlation between 68Ga-OPS202 tumour uptake with results from 
immunohistochemistry staining of sstr2. 
Avid is defined by the blinded readers at one of the acquisition timepoints as an easily 
identifiable lesion radiologically, where there has been clear focal uptake of 68Ga-OPS202 and 
approximately 1.5-fold uptake than the non-tumoural liver and lung parenchyma. 
 
1.2 
Study design 
This is a non-randomised, open-label, phase II study, with an approximately 4-week duration 
for each subject and central review-blinded reader endpoint. 
All subjects will receive a single dose of 68Ga-OPS202 (Investigational Imaging Product; IIP), 
consisting of a peptide mass up to 45 μg, with a radioactivity range of 150-200 MBq. 68Ga-
OPS202 is prepared up to 3 hours prior to administration by 68Ga-radiolabelling of an OPS202 
radiolabelling kit. 
Three PET acquisitions will be performed at 0.5, 1.0 and 2.0 hours post 68Ga-OPS202 
injection.18F-FDG-PET scan, which is part of routine clinical diagnosis, will be acquired at any 
time during the study period (including the Screening period), according to the investigator 
site’s standards.  
A single contrast enhanced computed tomography (ceCT) scan is required for the study.  This 
can be acquired after either of the two PET scans (18FDG-PET or 68Ga OPS202 post the 2-hour 
acquisition).  Thus, only one ceCT scan is required to minimize radiation dose.  Low-dose CT 
scans will be acquired for the other PET scans where the ceCT is not obtained. For the 68Ga-


IPSEN GROUP 
D-FR-01070-003 
CONFIDENTIAL  
 
SAP Final Version 2.0: 10 january 2020 
 
Page 10 of 39 
 
 
 
OPS202 PET scan a single low dose CT scan is preferred for the 0.5 and 1.0-hour post dosing 
acquisitions. 
All images will be sent to an imaging core laboratory (ICL) for central blinded reading by two 
independent experienced radiologists and/or nuclear medicine physicians and a third for 
adjudication of discordances. The readers will be specifically trained for this protocol. 
Study design scheme is presented in Figure 1. 
  
Figure 1 Study Design  
 
CT=computed tomography, h=hour, IIP=investigational imaging product, PET=positron emission tomography 
Note: Approximately 54 subjects will be screened to receive IIP to identify 16 sstr2 positive evaluable subject scans. 
  
1.2.1 
Study population 
Considering the estimated prevalence of sstr2 overexpression in breast cancer, it is anticipated 
that a total of approximately 54 subjects, in two specialised centres in Europe, will be enrolled 
in the study for 68Ga-OPS202 screening, to obtain around 16 sstr2 positive breast cancer (BC) 
evaluable subjects. However, when the ICL identifies 16 sstr2 positive evaluable subjects, with 
a minimum of two subjects having advanced disease, the study will be complete. 
Adults female subjects with newly diagnosed (early or advanced) breast cancer and Eastern 
Cooperative Oncology Group (ECOG) performance status of 2 or less will be recruited in this 
study. 
1.2.2 
Study exposure 
Subject participation in the study is estimated to last approximately 4 weeks and will include: 
• 
Visit 1: A screening period up to 14 days prior to IIP administration  
• 
Visit 2, Day 1: A single i.v. injection of between 150 MBq to 200 MBq of 68Ga-OPS202 
followed by PET acquisition at 0.5, 1 and 2 hours ±10 minutes post dosing 
Visit 3: A follow-up visit at Day 14 (±3 days) for evaluation of safety. Within the study 
an 18F-FDG-PET scan and also a ceCT scan must also be acquired. 
At the end of Visit 3, the subject’s participation in the study will end.  


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SAP Final Version 2.0: 10 january 2020 
 
Page 11 of 39
Overall duration of entire study, estimated as the time from set-up to close-out and reporting,
will be approximately 20 months. 
Futility Stopping Rule 
If less than three sstr2 positive evaluable subject scans out of 30 consecutive subjects screened 
with 68Ga-OPS202 PET/CT, or less than 8 out of 50, the study will be stopped.  
The Sponsor may consider stopping subject recruitment and revisit the study design with 
possible termination of the study when justified. 
1.3
Methods and procedures 
1.3.1
Subject identification and allocation to study treatment 
This is a non-randomised, single-arm phase II clinical study. After informed consent is 
obtained, subjects who are screened will be allocated a subject number. All screened subjects 
must be identifiable throughout the study. The investigator will maintain a list of subject 
numbers and names to enable records to be found at a later date if required. Subjects can be 
rescreened at a later date in the case of screening failure. 
Following confirmation of eligibility for the study at Visit 2, subjects will receive a single dose 
of 68Ga-OPS202 (IIP), consisting of a peptide mass up to 45 μg, with a radioactivity range of 
150-200 MBq activity of 68Ga. 
1.3.2
Subjects assessments 
1.3.2.1
Efficacy assessments 
For the primary, secondary and exploratory endpoints all the sets of images of the three time 
points obtained at Visit 2, one ceCT and one 18F-FDG-PET will be sent to an ICL for quality 
control and management of the reads. 
The centralised reads will be undertaken by two independent experienced radiologists and/or 
nuclear medicine physicians, and a third for adjudication of discordances for most of the reads.
The readers will be specifically trained for this protocol. 
All the images will be reviewed according to the workflow illustrated in Figure 2 and Figure 3
below. 


IPSEN GROUP 
D-FR-01070-003 
CONFIDENTIAL  
 
SAP Final Version 2.0: 10 january 2020 
 
Page 12 of 39 
 
 
 
Figure 2 Flow Chart of the Independent Review Methodology (68Ga-OPS202)  
 
 
Figure 3 Flow Chart of the Independent Review Methodology (18F-FDG-PET standard-of-truth) 
 
 
Full details of the read design and conduct are provided in the Independent Review Charter 
(IRC). 
For the primary endpoint analysis, the number of lesions and quality of the images will be taken 
into consideration by the readers. Scans will be blinded to subject identification, site and timing 
post injection. In case of discrepancy in lesion counts, images will go to the adjudicator (third 
reader) for a final read and adjudication. 


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CONFIDENTIAL 
SAP Final Version 2.0: 10 january 2020 
 
Page 13 of 39
For image quality, the readers will compare the three 68Ga-OPS202 PET/CT scans 
contemporaneously for each subject and note which image(s), if any, provides superior images 
based on overall image quality and lesion count. 
Details for computation and analysis of primary efficacy criterion are provided in section 
3.2.1.1.
The sequence of image display and recording of results will be as follows on a per subject basis:  
(1)
Review of the three image sets of 68Ga-OPS202 scans in randomised fashion with CT 
image fusion. The ceCT images acquired will be used for co-registration. Two readers 
will read and a third will adjudicate any differences. 
(2)
18F-FDG-PET images for standard-of-truth assessments will be reviewed by two 
radiologists not involved in 68Ga-OPS202 PET/CT images read, and the lesions mapped 
to the 68Ga-OPS202 read. Two readers will read and a third will adjudicate any 
differences. 
(3)
SUVmax and SUVmean calculations of the five most avid lesions per organ on 68Ga-
OPS202 PET scans (primary breast lesion, liver, lymph nodes, bone, lungs and brain) 
will be conducted by the ICL after identification of the lesions by one of the primary 
readers. 
(4)
Review of the lesion-to-background ratios in each major anatomical site (primary breast 
lesion, liver, lymph nodes, bone, lungs and brain) based on the evaluation of up to five 
most avid lesions per organ will be managed by the ICL after the lesions have been 
identified by one of the primary readers. 
(5)
For image quality, direct comparison of the three 68Ga-OPS202 scans acquired at 
different times, will be conducted for the primary breast cancer and then for all other 
lesions as the final step of the blinded read. The readers will be allowed to select whether 
one, two or all three acquisitions are optimal. The readers will be blinded to time point 
sequence. No adjudication will be required. 
(6)
The 68Ga-OPS202 PET scans will be compared with the 18F-FDG-PET scans (with 
ceCT).  
1.3.2.2
Safety assessments 
• 
Adverse Events 
Adverse events (AEs) will be monitored from the time that the subject gives informed consent 
and throughout the study. AEs will be elicited by direct, nonleading questioning or by 
spontaneous reports.  
AEs will be recorded and graded according to the current version of the National Cancer 
Institute Common Terminology Criteria for AEs (version 5.0, Dated 14 February 2018).
• 
Vital signs 
Vital signs will be collected at Screening (Visit 1), IIP administration visit (Visit 2 Day 1 before 
IIP administration and at 0.5, 1, 2, 4 hours post-injection and on Day 2), and End of Study (Visit 
3)/Early Withdrawal. 


IPSEN GROUP 
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CONFIDENTIAL  
 
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Blood pressure (systolic and diastolic) and heart rate will be assessed with an automated device 
so that measurements are independent of the observer. These parameters will be recorded after 
five minutes rest in sitting position and after one minute standing.  
Respiratory rate and temperature (tympanic/oral) will also be recorded. 
Any clinically significant abnormalities will be recorded as AEs. 
 
• 
Physical Examination 
Physical examination and body weight will be conducted at Screening (Visit 1), IIP 
administration visit (Visit 2 Day 1, Pre-Dose), and End of Study (Visit 3)/Early Withdrawal. 
Height will be measured at Screening. 
Any clinically significant physical examination findings (abnormalities) observed during the 
study will be reported as AEs. Any physical examination findings (abnormalities) persisting at 
the end of the study will be followed by the investigator until resolution or until reaching a 
clinically stable endpoint. 
 
• 
Electrocardiography 
Electrocardiograms (ECGs) will be recorded at Screening Visit and EOS/EW (Visit 3).  
Twelve-lead ECGs will be recorded at a paper speed of 25 mm/sec so that the different ECG 
intervals (RR interval, PR interval, QRS interval, QT and QTc) can be measured automatically 
as per study site usual practice. 
The ECG will be recorded with the subject in supine position after five minutes of rest until 
four regular consecutive complexes are available. ECG interval estimates will be measured as 
per study site usual practice, in this study. 
Any clinically significant abnormalities will be recorded as AEs. 
 
• 
Clinical Laboratory Tests 
Blood samples will be collected at all study visits (Screening Visit [Visit 1], Day 2 [Visit 2], 
and End of Study/Early Withdrawal [Visit 3]) for the evaluation of haematology and serum 
chemistry.  
Fresh urine samples will be collected at all study visits for dipstick urinalysis. 
The investigator will review the safety laboratory test results, document the review, and record 
any clinically relevant result occurring or observed during the study in the AE section of the 
eCRF. 
 
Haematology – the following parameters will be assessed: red blood cell (RBC) count, 
haemoglobin, haematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin 
(MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cell (WBC) 
absolute count (neutrophils, lymphocytes, monocytes, eosinophils, basophils, and others) and 
platelet count. 
Blood Biochemistry – the following parameters will be assessed: urea, creatinine, creatinine 
clearance, total bilirubin, conjugated bilirubin, chloride, bicarbonate, sodium, potassium, 
calcium, phosphate, alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine 


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aminotransferase (ALT), gamma-glutamyl transferase (GGT), albumin, total protein, total 
cholesterol, triglycerides, fasting glucose 
 
Urinalysis – the following parameters will be assessed:  pH, protein, ketones, bilirubin, blood, 
urobilinogen, nitrites, leukocyte esterase, glucose and specific gravity by dipstick. 
Microscopy will be performed, if indicated, but results will not be collected in the eCRF. If in 
the opinion of the investigator there are any clinically significant abnormalities in microscopy, 
they will be recorded as an AE in the eCRF. 
 
Pregnancy - A pregnancy test will be performed for all female subjects of childbearing 
potential at each visit: ß-HCG test at Screening and End of study and urinary hCG test at Visit 
2 Day 1 before IIP administration). 
 
1.3.2.3 
Other assessments 
The following assessments will be performed at Screening visit (Visit 1), that will take place 
within the 2-week period prior to the first 68Ga-OPS202 administration: 
• 
Demographic data (year of birth/age, sex and race/ethnicity will be collected according 
to individual country regulations/requirements).  
• 
Subject disposition information 
• 
Medical and surgical history, including ongoing conditions 
• 
Prior and concomitant medications/therapies 
• 
Prior and concomitant non-drug therapies  
• 
Concomitant surgical procedures 
• 
Collection of historical paraffin embedded breast tumour blocks or slides with 
anatomical location of the lesion (s) indicated. 
 
1.3.2.4 
Withdrawal/discontinuation 
A subject may discontinue participation in the study at any time for any reason (e.g. withdrawal 
of consent, AE). The investigator and/or sponsor can withdraw a subject from the study at any 
time for any reason (e.g. protocol deviation as defined in Section 13.1.2 of the protocol, 
noncompliance with the protocol conditions or AE). All cases of discontinuation will be 
discussed between the investigator and the sponsor.  
 
The subject’s participation in the study will be considered to have ended at the time of the last 
visit (Visit 3, at Day 14±3 days). For subjects who complete the study, final evaluations will be 
performed on Day 14 (±3 days) after the subject receives the IIP. 


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If a subject decides to withdraw from the study after the administration of IIP, or the investigator 
decide to withdraw the subject, all efforts will be made to complete and report the observations 
up to the time of withdrawal as thoroughly as possible. A complete final evaluation at the time 
of the subject’s withdrawal should be made and an explanation given of why the subject is 
withdrawing or being withdrawn from the study. 
In case subject is lost to follow-up, date of termination will be specified, and the EW visit will 
be performed if possible.   
1.3.3
Schedule of assessments 
The schedule of procedures and assessments during the study is summarised in Table 1.
Table 1 Study Procedures and Assessments 
Study Visits [a]
Screening
Visit 1
Day -14 to -1
Visit 2[a]
Day 1
Visit 2[a]
Day 2
End of Study/Early 
Withdrawal Visit 3
Day 14 (±3)
Informed consent [b]
X
Eligibility criteria
X
X
Demographics [c]
X
Medical history [d]
X
Prior therapies [d]
X
Concomitant therapies [e]
X
X
X
X
Physical examination [f]
X
X
X
Vital signs [g]
X
X
X
X
ECG [h]
X
X
Haematology [i]
X
X
X
Blood chemistry [j]
X
X
X
Urinalysis [k]
X
X
X
Pregnancy test [l]
ßHCG
(blood test)
Urinary HCG
ßHCG
(blood test)
68Ga-OPS202 PET/CT 
imaging [m]
X
18F-FDG-PET scan [n]
Any time during the study period
Contrast enhanced CT[m]
With 68Ga-OPS202 PET or 18F-FDG-PET 
Adverse events [o]
X
X
X
X
Compliance [p]
X
Biopsy [q]
X
AE=adverse event, CT=computed tomography, ECG=electrocardiogram, 18F-FDG=18F-fluorodeoxyglucose, HCG=human 
chorionic gonadotropin, HER2= human epidermal growth factor receptor 2, ICL=imaging core laboratory, IIP=investigational 
imaging product, PET=positron emission tomography. 
(a)
Study visits: Screening Visit up to 14 days before IIP administration; Subjects may be hospitalised overnight at the 
discretion of the investigator at Visit 2. All subjects (either hospitalised or not) will attend consultation on Day 2, 
which is part of Visit 2, for: review of AEs, new or changed concomitant medications, vital signs, physical 
examination, haematology, biochemistry, urinalysis. 
(b)
Informed consent: Must be obtained prior to undergoing any study specific procedures and will occur prior to the 
2-week screening period. 
(c)
Demographics: Age, sex and self-reported race/ethnicity if authorised to be collected in the country. 
(d)
Medical history and prior therapies: To include clinically significant diseases, surgeries, cancer history and all 
relevant medications. 
(e)
Concomitant medications: Dose and indication will be recorded from 3 months prior to the IIP administration, at 
study entry and at each visit. Once the subject has withdrawn from/completed the study, concomitant medications and 
treatments should be recorded until all study treatment-related toxicities have resolved. 
(f)
Physical examination: Major body systems, body weight, height (screening visit only)  


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(g) 
Vital signs: 0.5, 1, 2 and 4 hours post-injection (supine and standing systolic and diastolic blood pressure and heart 
rate, body temperature, respiratory rate). 
(h) 
ECG: Twelve-lead ECGs will be recorded at a paper speed of 25 mm/sec so that the different ECG intervals (RR, PR, 
QRS, QT) can be measured automatically as per study site usual practice. The ECG will be recorded with the subject 
in supine position after five minutes of rest until four regular consecutive complexes are available. 
(i) 
Haematology: Red blood cell (RBC) count, haemoglobin, haematocrit, mean corpuscular volume (MCV), mean 
corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cell (WBC) 
count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils, and others) and platelet count. 
(j) 
Blood chemistry: urea, creatinine, creatinine clearance, chloride, bicarbonate, sodium, potassium, calcium, phosphate, 
total bilirubin, conjugated bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, 
gamma-glutamyl transferase, albumin, total protein, total cholesterol, triglycerides, fasting glucose. 
(k) 
Urinalysis: Dipstick for pH, protein, ketones, bilirubin, blood, urobilinogen, nitrites, leukocyte esterase, glucose and 
specific gravity. 
(l) 
Pregnancy test: A pregnancy test will be performed at each visit particularly before 68Ga-OPS202 administration. 
(m) 
68Ga-OPS202 PET/CT imaging: PET acquisition at 0.5, 1 and 2 hours after 68Ga-OPS202 administration.  Iodinated 
i.v. CT contrast imaging (chest, abdomen, pelvis and brain). A single contrast enhanced computed tomography (ceCT) 
scan is required for the study. This can be acquired after either of the two PET scans (18FDG-PET or 68Ga-OPS202 
post the 2-hour acquisition). Low-dose CT scans will be acquired for the other PET scans where the ceCT is not 
obtained (see the Imaging Review Charter (IRC)). Anonymised and blinded to acquisition time images will be sent to 
the ICL. 
(n) 
18F-FDG-PET scan: 18F-FDG-PET scan, which is part of routine clinical diagnosis, will be performed during the 
study period and images sent to ICL. A ceCT or a low dose CT may be performed with the 18F-FDG-PET (see the 
Imaging Review Charter (IRC) 
(o) 
Adverse events: Subjects must be followed for AEs, regardless of relationship to IIP, from the time they signed the 
informed consent until 14±3 days after the dose of IIP. Clinically significant changes in physical examination, vital 
signs, electrocardiogram and laboratory findings will be recorded as an AE. The investigator will follow-up AEs until 
resolution or stabilisation. 
(p) 
Compliance: The peptide mass dose and the radioactivity dose injected will be recorded at Visit 2. 
(q) 
Biopsy: To be performed if not already done. Tumour biopsy, which is not a prerequisite for inclusion, is routinely 
performed for confirmation and staging of the disease, as well as classification according to hormone receptor status 
and HER2 status. For the study, an archived tumour sample (block is preferred over paraffin embedded slides) is 
required for the evaluation of sstr2 expression by immunohistochemistry staining.  
 
1.3.4 
Planned sample size 
It is anticipated that a total of 54 subjects will be enrolled in the study for 68Ga-OPS202 
screening, to obtain around 16 sstr2 positive BC evaluable subjects. Considering the estimated 
prevalence of sstr2 overexpression in breast cancer, the overall number of subjects to be 
administered 68Ga-OPS202 in the study will be over 50. However, when the ICL identifies 16 
sstr2 positive evaluable subjects, with a minimum of two subjects with advanced disease, the 
study will be complete. 
This estimation of 16 sstr2 positive BC evaluable subjects is considered appropriate for a 
descriptive analysis and it is not based on a formal statistical sample size calculation. In the 
event that a subject misses an imaging exam and/or measurement relevant to the primary and 
key secondary endpoints, an additional subject will be recruited to ensure an adequate sample 
size in the sstr2 positive BC evaluable set. 
 
2 
SUBJECT POPULATIONS (ANALYSIS SETS) 
 
The following populations will be used during statistical analyses: 
• 
Eligibility screened population: All subjects screened (i.e. who signed the informed 
consent).  
• 
Safety population: All subjects who received the dose of study IIP. 


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• 
68Ga-OPS202 screened population: All subjects who received the dose of study IIP and 
for whom PET/CT scan images are readable for at least one timepoint. This population 
encompasses both subjects with sstr2 positive lesion(s) and those with sstr2 negative 
lesions (no avid lesion with 68Ga-OPS202).   
• 
Sstr2 positive population: All subjects who received the dose of study IIP and for whom 
68Ga-OPS202 PET/CT scan images are readable for at least one timepoint and have one 
avid lesion identified by central readers, 18F-FDG-PET/CT scan and a ceCT scan 
confirmed by the central readers. 
• 
Sstr2 positive evaluable population: 68Ga-OPS202 sstr2 positive population with at 
least two evaluable 68Ga-OPS202 timepoints, 18F-FDG-PET/CT scan and a ceCT scan 
confirmed by the central readers. A 68Ga-OPS202 timepoint is considered evaluable if it 
shows at least one avid lesion. 
 
Study populations are summarized in the figure below. 
Figure 4 Study populations 
 
For each population of analysis, further description and specificities are provided below. 


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2.1 
Efficacy populations 
2.1.1 
68Ga-OPS202 screened population 
The 68Ga-OPS202 screened population includes all subjects who received the dose of study IIP 
with one or more readable 68Ga-OPS202 PET and a readable ceCT scan.  
The assessment of 68Ga-OPS202 PET scan and ceCT scan readability will be based on the 
imaging read named “Confirmation read”, provided by ICL. 
This population encompasses both subjects with sstr2 positive lesion(s) and those with sstr2 
negative lesions (i.e. no avid lesion with 68Ga-OPS202).  
 
2.1.2 
Sstr2 positive population 
The sstr2 positive population includes all subjects who received the dose of study IIP and for 
whom 68Ga-OPS202 PET/CT scan images are readable for at least one timepoint and have one 
avid lesion identified by central readers.  
The assessment of 68Ga-OPS202 PET scan readability and the presence of avid lesions will be 
based on the imaging read named “Confirmation read”, provided by ICL. 
Subjects are also required to have a 18F-FDG-PET/CT scan and a readable ceCT scan. 
 
2.1.3 
 Sstr2 positive evaluable population 
The sstr2 positive evaluable population includes all subjects from the 68Ga-OPS202 sstr2 
positive population with at least two evaluable timepoints. Subject are also required to have a 
18F-FDG-PET/CT scan and a readable ceCT scan.  
 
Evaluable subjects are those with a ceCT scan, 18F-FDG-PET scan and at least two 68Ga-
OPS202 PET scans that are readable (three images are to be acquired but two of these must be 
readable by the central readers. If only two PET scans are acquired both must be readable) with 
at least one avid lesion identified on at least 2 timepoints by central readers. 
The assessment of 68Ga-OPS202 PET scan readability and the presence of avid lesions will be 
based on the blinded imaging read “68Ga-OPS202 PET Independent Review” (two readers and 
potential adjudication), provided by ICL. 
  
Listings of subjects regarding inclusion in each population and satisfying the population 
definition and associated data will be reviewed by the study team. 
The reasons for subject exclusion from each of the populations will be listed and tabulated. 
 
2.2 
Safety population 
The safety population includes all subjects who received the dose of study IIP. 
A subject who received IIP but did not sign the informed consent will be included into the safety 
population. 
 


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2.3
Primary population 
The co-primary analysis based on the primary efficacy endpoint to determine sstr2 positive 
percentage will use the 68Ga-OPS202 screened population as the denominator. The co-primary 
analysis based on the primary efficacy endpoint to assess optimum imaging timing of the PET 
scan following 68Ga-OPS202 injection will be performed on the sstr2 positive evaluable 
population.  
In addition, as a supportive post-hoc analysis, the sstr2 positive prevalence may also be 
evaluated on the agreed optimum timepoint population. 
All secondary and exploratory efficacy endpoints will be evaluated on the sstr2 positive 
evaluable population.  
The assessment of safety and tolerability will be based on the safety population. 
3
STATISTICAL METHODS 
3.1
Statistical analysis strategy 
The statistical analyses will be performed in accordance with International Conference on 
Harmonisation (ICH) E9 guideline [1] and will be based on the pooled data from the individual 
study sites, unless otherwise stated.
Statistical analyses will be performed by Covance Clinical Development SARL. 
3.1.1
Primary efficacy endpoints 
The co-primary efficacy endpoints are: 
(a)
Percentage of subjects with sufficiently avid lesion(s) to be identified as a sstr2 positive 
lesion. (Avid is defined by the blinded readers at one of the acquisition timepoints as an 
easily identifiable lesion radiologically, where there has been clear focal uptake of 68Ga-
OPS202 and 1.5-fold or greater uptake than the non-tumoural liver and lung parenchyma).


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(b) 
Differences in the number of lesions detected by 68Ga-OPS202 between the three PET 
acquisition timepoints (0.5, 1 and 2 hours), and reader interpretation of optimal image(s) 
in the primary breast lesions. The optimum image acquisition time could be one, two or all 
three acquisitions timepoints i.e. no noticeable difference between 0.5, 1 and 2 hours post 
infusion. 
 
3.1.2 
Secondary efficacy endpoints 
Key Secondary Endpoint:  
(c) 
Differences in the number of lesions detected by 68Ga-OPS202 between the three PET 
acquisition timepoints (0.5, 1 and 2 hours), and reader interpretation of optimal image(s) 
in nodular and metastatic lesions. Significant uptake of 68Ga-OPS202 for the evaluation 
of a lesion is an avid lesion defined by the blinded readers at one of the acquisition 
timepoints as an easily identifiable lesion radiologically, where there has been clear focal 
uptake of 68Ga-OPS202 and 1.5-fold or greater uptake than in the non-tumoural liver and 
lung parenchyma. 
(d) 
The SUVmean and SUVmax in the primary lesion between each of the three timepoints, 
measured in the most avid lesions (using the 68Ga-OPS202 scans). This is assessed by 
the tumour-to-background ratio in the primary tumour and each of the major anatomic 
sites (liver, lymph nodes, bone, lungs and brain). The background consists of non-
tumoural liver parenchyma or aortic blood where sufficient liver is not available. 
Identification of lesions to be used will be made by one of the two primary readers. 
Other Secondary Endpoints: 
(e) 
Differences in relative lesion counts as a ratio of the number of lesions detected by 68Ga-
OPS202 at 0.5, 1 and 2 hours post dose respectively, compared to the number of lesions 
assessed by standard-of-truth (descriptive analyses). The standard-of-truth is the 18F-
FDG-PET/CT scan images acquired at any time during the study period (including the 
Screening period). This will be calculated by (number of lesions detected by 68Ga-
OPS202)/(number of lesions detected by 18F-FDG-PET). 
(f) 
Differences of absolute number of lesions between the three PET acquisition timepoints 
detected in each of the following anatomic sites: 
• 
Lymph nodes 
• 
Liver 
• 
Axial/appendicular skeleton   
• 
Lungs 
• 
Brain 
(g) 
The primary and secondary endpoints will also be evaluated on a radioactivity dose/kg 
of body weight. 
 
Exploratory Endpoints: 
(h) 
Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging of breast cancer expressing 
sstr2 positive by both subject-based and lesion-based analysis compared to standard-of-
truth 


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(i) 
SNR calculated from lesion-free volume of interest (VOI) in the liver: SUVmean/SUVSD 
at the three PET acquisition timepoints  
(j) 
Estimated correlation in terms of number of avid lesions between 68Ga-OPS202 PET at 
the agreed “optimum timepoint” and 18F-FDG-PET  
(k) 
Estimated 
correlation 
between 
68Ga-OPS202 
PET 
uptake 
and 
results 
of 
immunohistochemistry staining of sstr2 of the primary tumour. 
 
3.1.3 
Safety endpoints 
The safety and tolerability of 68Ga-OPS202 will be assessed throughout the study by evaluating 
AEs, clinically significant abnormalities in laboratory tests (serum chemistry, haematology, and 
urinalysis), vital signs measurements (including blood pressure and heart rate), physical 
examination findings and body weight measurements, ECG findings, relevant medical history 
and concomitant medication/therapies usage. 
The following safety endpoints will be evaluated: 
• 
Percentage of subjects experiencing at least one AE of any grade according to the 
National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-
CTCAE) version 5.0, including any serious adverse events (SAEs) and suspected 
unexpected serious adverse reactions (SUSARs). All AEs will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) and 
preferred term (PT) (as per most recent version). 
• 
Percentage of subjects experiencing at least one AE of grade ≥3 according to NCI 
CTCAE. 
• 
Clinically significant changes in physical examination, vital signs, ECG and laboratory 
findings, which will be recorded by the investigator as AEs. 
 
3.1.4 
Multiplicity 
No multiple testing will be performed in this study. 
 
3.1.5 
Significance testing and estimation 
The statistical analysis of efficacy and safety is only descriptive, therefore no formal statistical 
significance testing will be performed. 
 
3.2 
Analysis methods 
3.2.1 
Efficacy 
All efficacy analyses will be based on the centralised review of scans imaging performed under 
the responsibility of the ICL. 
As specified in the description of each efficacy criterion thereafter, analysis will be based on 
PET/CT assessments for lesion count endpoints (absolute number of lesions, relative lesion 
count, image quality and diagnostic sensitivity) and on PET assessments alone for SUV related 
assessments. 
The standard-of-truth (SOT) is the 18F-FDG-PET/ceCT scan images acquired at any time during 
the study period (including the Screening period). 


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Due to decision of study premature termination, several analyses and/or outputs were removed. 
3.2.1.1 
Primary efficacy analysis  
 
First component of the co-primary endpoint 
The first component of the co-primary endpoint is the percentage of subjects with sufficiently 
avid lesion(s) to be identified as a sstr2 positive lesion, i.e. the sstr2 positive prevalence in this 
study population. Avid is defined by the blinded readers at one of the timepoints as an easily 
identifiable lesion radiologically, where there has been clear focal uptake of 68Ga-OPS202. 
This will be a simple percentage calculation: 
ʹ
ൌ
ܰݑܾ݉݁ݎ݋݂ݏݑܾ݆݁ܿݐݏ݅݊ݏݏݐݎʹ݌݋ݏ݅ݐ݅ݒ݁݌݋݌ݑ݈ܽݐ݅݋݊
ܰݑܾ݉݁ݎ݋݂ݏݑܾ݆݁ܿݐݏ݅݊͸ͺܩܽെܱܲܵʹͲʹݏܿݎ݁݁݊݁݀݌݋݌ݑ݈ܽݐ݅݋݊ 
A listing with the subjects in sstr2 positive population and the subjects in the 68Ga-OPS202 
screened population will be provided in order to allow computing this percentage.  
 
Second component of the co-primary endpoint 
The second component of the co-primary endpoint is based on both image quality and lesion 
count using the sstr2 positive evaluable population. 
The selection of the optimal PET acquisition time will be done by choosing the timepoint with 
superior images based on overall image quality and observed higher number of lesions detected. 
 
The number of lesions detected by 68Ga-OPS202 in the primary breast lesions will be reported 
at each of the three PET acquisition timepoints (0.5, 1 and 2 hours). 
 
Individual values of number of lesions detected by 68Ga-OPS202 in the primary breast lesions 
(result from both readers as well as final result) will be listed by subject and by PET acquisition 
timepoint. 
 
Image quality 
After blinded reading, the readers will compare the three scans (the three acquisitions of 68Ga-
OPS202) contemporaneously for each subject and note which image(s), if any, provides 
superior images based on overall image quality and lesion count. 
 
This qualitative assessment will be performed using a quality score. 
 
For each PET/CT assessment, each independent blinded reader will perform a direct 
comparison of the three 68Ga-OPS202 scans acquired at different times (0.5, 1 and 2 hours) in 
the primary breast lesions. The readers will be allowed to select whether one, two or all three 
acquisitions are optimal, attributing a score for each assessment. The readers will be blinded to 
timepoint sequence.   


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The score for the assessment having superior images will be set to “1”, and score for the 
assessments not selected will be set to “0”. In case two assessments are considered optimal and 
of equal quality, both assessments will have a score of “1” and the third one will be set to “0”. 
In case of equal quality between the three scans, the three assessments will have a score of “1”. 
Values will be available in the database provided by ICL. 
In case a timepoint has been assessed as “non-readable” for the reader, the given timepoint will 
not be available for comparison, and therefore will have a missing quality score for that reader. 
Individual values of quality score for primary breast lesions and reason for selecting scan will 
be listed per reader, by subject and by PET acquisition timepoint.  
   
3.2.1.2 
Secondary efficacy analysis 
 
All secondary and exploratory analyses will be performed using the sstr2 positive evaluable 
population only.  
Similar to the primary endpoint, the selection of the optimal PET imaging time of 68Ga-OPS202 
will be based on the provided outputs for all secondary and exploratory efficacy endpoints.  
 
Key Secondary Endpoint: 
 
a) 
Absolute number of lesions detected by 68Ga-OPS202 in nodular and metastatic lesions 
For each PET/CT assessment, the individual number of lesions detected by 68Ga-OPS202 in 
nodular and metastatic lesions (result from both readers as well as final result) will be listed by 
subject and by PET acquisition timepoint. If there is a high number of lesions (≥35 lesions) in 
any one organ, identifying and counting of the lesions is not feasible as it cannot be accurately 
done. The absolute number of lesions will be presented as a category “≥35 lesions” if such case 
occurs.   
Values will be available in the database provided by ICL. 
 
A listing of all discrepancies between both readers in the nodular and metastatic lesions will 
also be presented by subject and PET acquisition timepoint. 
 
Image quality 
For each PET/CT assessment, each independent blinded reader will perform a direct 
comparison of the three 68Ga-OPS202 scans acquired at different times (0.5, 1 and 2 hours) in 
nodular and metastatic lesions. 
Individual values of quality score for nodular and metastatic lesions and reason for selecting 
scan will be listed per reader, by subject and by PET acquisition timepoint 
 
b) 
Lesion SUVmax and tumour-to-background ratio 
Lesion SUVmax  
For each PET assessment, the SUVmax (unit-less measure) will be measured for each lesion, up 
to a maximum of the five most avid lesions per organ identified by one of the primary readers.  


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In order to obtain a unique measure per organ, the mean of the SUVmax will be computed within 
each of the six following organs:  
• 
Primary breast lesion  
• 
Liver 
• 
Lymph nodes  
• 
Bone 
• 
Lungs 
• 
Brain. 
 
Values will be available in the database provided by ICL. 
Tumour-to-background ratio  
For each PET assessment, the tumour-to-background ratio will also be measured for each 
lesion, up to a maximum of the five most avid lesions per organ, as follow: 

ൌ
ܮ݁ݏ݅݋݊ܷܸܵ݉݁ܽ݊
ܷܸܵ݉݁ܽ݊݋݂ݐ݄݁ݏݑܾ݆݁ܿݐᇱݏݎ݂݁݁ݎ݁݊ܿ݁ݐ݅ݏݏݑ݁ሺݐݑ݉݋ݑݎ݂ݎ݁݁݈݅ݒ݁ݎכሻ 
*If insufficient tumour free liver is available for reference tissue, then aortic blood pool will be used as background.  
 
The tumour-to-background ratio will be obtained using the mean of all lesions tumour-to-
background ratios for each of the six following organs:  
• 
Primary breast lesion  
• 
Liver 
• 
Lymph nodes  
• 
Bone 
• 
Lungs 
• 
Brain. 
Tumour-to-background ratio is a unit-less measure where a high tumour-to-background ratio 
indicates high effectiveness of 68Ga-OPS202 as a diagnostic agent, in a similar manner to 
SUVmax. 
 
Individual values of the lesion SUVmax, lesion SUVmean, SUVmean of the subject’s reference 
tissue and tumour-to-background ratio will be listed by subject, by each of the six organs and 
by PET acquisition timepoint.  
 
Other Secondary Endpoints: 
 
c) 
Relative lesion count 
The relative lesion count is the ratio of the number of lesions detected by 68Ga-OPS202 at each 
of the three PET acquisition timepoints compared to the number of lesions assessed by standard-
of-truth (18F-FDG-PET scan).  
For each PET/CT assessment, this ratio will be computed as indicated below: 


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ܴ݈݁ܽݐ݅ݒ݁݈݁ݏ݅݋݊ܿ݋ݑ݊ݐ ൌܰݑܾ݉݁ݎ݋݂݈݁ݏ݅݋݊ݏ݀݁ݐ݁ܿݐ݁݀ܾݕ͸ͺܩܽെܱܲܵʹͲʹ
ܰݑܾ݉݁ݎ݋݂݈݁ݏ݅݋݊ݏ݀݁ݐ݁ܿݐ݁݀ܾݕͳͺ	 െ	
 െ 
 
Relative lesion count will be computed over all lesions of all organs and for each of the 
following organs: 
• 
Primary breast tumour (among all subjects with at least one lesion detected by 18F-FDG-
PET in primary breast tumour). 
• 
Lymph nodes (among all subjects with at least one lesion detected by 18F-FDG-PET in 
lymph nodes). 
• 
Liver (among all assessed subjects with at least one lesion detected by 18F-FDG-PET in 
liver). 
• 
Axial/appendicular skeleton (bone) (among all assessed subjects with at least one lesion 
detected by 18F-FDG-PET in bone). 
• 
Lungs (among all assessed subjects with at least one lesion detected by 18F-FDG-PET in 
lungs) 
• 
Brain (among all assessed subjects with at least one lesion detected by 18F-FDG-PET in 
brain). 
For the per organ analysis, the relative lesion count will be: 
• 
Equal to 0 if there is no lesion identified in the specific organ on 68Ga-OPS202 scan.  
• 
Missing if the numerator is missing (for example in case of non-readable 68Ga-OPS202 
PET scan at timepoint) with non-null denominator 
• 
Not analyzed if there is no lesion identified in the specific organ on 18F-FDG-PET scan. 
If there are 35 lesions or more counted on both 68Ga-OPS202 and 18F-FDG-PET scans, then the 
relative lesion count will be set to 100%. If any of the two scans has a count of ≥35, the relative 
lesion count will be computed using a count of 35 lesions for the scan showing more than 35 
lesions.    
 
Individual values of the relative lesion count will be listed by subject, by organ and by PET 
acquisition timepoint. 
 
d) 
Absolute number of lesions detected by 68Ga-OPS202 in lymph nodes, liver, 
Axial/appendicular skeleton, lungs and brain 
For each PET/CT assessment, the number of lesions detected by 68Ga-OPS202 will be reported 
for each of the five following anatomic sites: 
• 
Lymph nodes 
• 
Liver 
• 
Axial/appendicular skeleton (Bones) 
• 
Lungs 
• 
Brain 
Values will be available in the database provided by ICL. 
Individual values of the number of lesions detected by 68Ga-OPS202 (results from both readers 
and final result) will be listed by subject, organ and PET acquisition timepoint. 


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e) 
The second component of the co-primary and appropriate secondary endpoints will also 
be evaluated on a radioactivity dose/kg of body weight. 
This analysis will not be provided. 
 
Exploratory efficacy endpoints: 
 
f) 
Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging of breast cancer expressing 
sstr2 positive by both subject-based and lesion-based analysis compared to standard-of-
truth 
This analysis will not be provided. 


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g) 
SUVmax ratio for lesions  
This analysis will not be provided. 
 
h) 
SNR  
For the primary breast lesions, the SNR will be computed as follows: 
ܴܵܰൌ
ܷܸܵ௠௘௔௡
ܷܸܵௌ஽݋݂ݐ݄݁ݏݑܾ݆݁ܿݐᇱݏݎ݂݁݁ݎ݁݊ܿ݁ݐ݅ݏݏݑ݁ሺݐݑ݉݋ݑݎെ݂ݎ݁݁݈݅ݒ݁ݎכሻ 
*If insufficient tumour free liver is available for reference tissue, then aortic blood pool will be used instead.  
 
Values will be available in the database provided by ICL.  
A higher SNR indicates higher effectiveness of 68Ga-OPS202 as a diagnostic agent. 
Individual values of SNR will be listed by subject and by PET acquisition timepoint.  
 
i) 
Estimated correlation in terms of number of avid lesions between 68Ga-OPS202 PET at 
the agreed “optimum timepoint” and 18F-FDG-PET 
This analysis will not be provided. 
 
j) 
Estimated 
correlation 
between 
68Ga-OPS202 
PET 
uptake 
and 
results 
of 
immunohistochemistry staining of sstr2 of the primary tumour. 
This analysis will not be provided. 


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3.2.2
Safety 
All safety data will be provided in both data listings and summary tables and using the Safety 
population.
3.2.2.1
Adverse events 
All AEs will be recorded and graded by investigators using the NCI CTCAE classification 
(Version 5.0), will be coded using the MedDRA Version 20.1 or higher, and will be classified 
by MedDRA PT and SOC.
Listings will be presented and sorted by subject number, start date of AEs, primary system 
organ class, preferred term and verbatim text for all adverse events recorded during the study.
Listings of SAEs, AEs leading to IIP withdrawal and AEs leading to death (fatal outcome) will 
also be presented. Also, a listing of grade ≥3 AEs will be provided. 
Treatment Emergent Adverse Events (TEAEs) will be flagged (*) in the AE listings and will 
be summarised. 
A TEAE is defined as any AE that occurs during the study if:  
(1)
it was not present prior to receiving the 68Ga-OPS202 injection, or  
(2)
it was present prior to receiving the 68Ga-OPS202 injection but the grade increased 
during the study, or  
(3)
it was present prior to receiving the 68Ga-OPS202 injection, the grade is the same but the 
causality changed to “related” during the study.  
An overall summary table of all AEs will be presented.  
In that table, in the cross classification of causality and intensity, any subject experiencing 
multiple AEs with different intensities for each causality category will be counted for each 
grade. 
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3.2.2.2 
Laboratory data 
A separate listing of normal ranges for Standard International (SI) units will be provided by age 
where relevant. 
Laboratory data (serum haematology and biochemistry panels, urinalysis) will be listed in SI 
units and abnormal values will be flagged (high [H], low [L], clinically significant [C], NCI-
CTC grade (G)) where applicable. Any unscheduled laboratory assessments will be flagged [U] 
in the listings.  
 
Subject listings will be presented by subject number and visit. 
 
• 
Haematology and Biochemistry 
For haematology and biochemistry parameters, the baseline will be defined as the last 
measurement collected prior to IIP administration (Visit 2 Day 1). 
Shift tables for haematology and biochemistry parameters will be presented of the number and 
percentage of subjects with low, normal or high values. 
Haematological and biochemistry toxicities will be recorded and graded according to the NCI-
CTC criteria, Version 5.0. The NCI-CTC grade 3 and 4 haematology and biochemistry 
parameters by subject and by visit will be listed. Listings of the laboratory parameters in 
appendix 2 section 14.3.4 will include listings of NCI-CTC Grade 3 and 4 haematological 
toxicities, listings of NCI-CTC Grade 3 and 4 biochemical toxicities and listings of out of range 
biochemistry parameters that could not be graded using NCI-CTC grade (below Lower Limit 
of Normal range (LLN) – normal – above Upper Limit of Normal range (ULN).  
 
• 
Urinalysis 
For categorical urinalysis data (absent/trace/positive of protein, ketones, bilirubin, blood, 
urobilinogen, nitrites, leukocyte esterase and glucose), frequency tables will be presented at 
each scheduled assessment (Baseline, post-dose, EOS/EW). 


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3.2.2.3 
Vital signs  
Vital signs (body temperature, supine and standing blood pressure and heart rate, respiratory 
rate), body weight and BMI will be listed at each assessment by subject. Any unscheduled vital 
signs will be flagged [U] in the listing.   
Baseline values will be defined as the last vital signs measurement collected prior to IIP 
administration. 
Summary statistics will be presented at each scheduled assessment for actual values and 
changes from baseline. 
Following assessments will be summarised for body temperature, blood pressure, heart rate and 
respiratory rate: Baseline, 0.5h Post-dose, 1h Post-dose, 2h Post-dose, 4h Post-dose, Visit 2 Day 
2, EOS/EW. 
Weight and BMI will be analysed at Baseline, Visit 2 Day 2 and EOS/EW. 
 
3.2.2.4 
ECG 
ECG results will be listed at each assessment (Screening, EOS/EW) by subject. Any 
unscheduled ECG will be flagged [U] in the listings. 
Baseline will be defined as the last ECG measurement collected prior to IIP administration. 
For continuous ECG parameters (RR duration, PR duration, QRS duration, QT duration, QTc 
Bazett, QTc Fridericia, QTc manual) summary statistics will be presented at each scheduled 
assessment for actual values and changes from baseline. 
For interpretation of clinical significance (within normal limits / abnormal, not clinically 
significant / abnormal, clinically significant / not evaluable), a frequency table will be presented 
at each post-dose assessment as well as the changes from baseline with the following categories: 
improved, stable, worsened, clinically significant worsening. 
 
3.2.2.5 
Physical examination 
Physical examination (normal, abnormal, specification for abnormal result) will be listed by 
subject number and visit. Any unscheduled physical examination will be flagged [U] in the 
listings. 


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3.2.3 
Missing data and outliers 
 
3.2.3.1 
Missing data 
• 
Efficacy endpoints 
No imputations will be made for missing data. 
• 
Safety endpoints 
If a value requires a retest (for laboratory values, vital signs, ECG), the closest non-missing 
reliable value to the scheduled visit is used in the summary tables. An assessment is considered 
reliable if it is performed without any technical problem or altered blood samples and if the 
result is within the range of plausible values. 
Any repeat or additional assessments performed will be included in the individual subject data 
listings. 
For AEs with missing information for the intensity and/or causality, the value will not be 
replaced and will be summarised as a separate category.  
For all other variables, no imputations will be made for missing data. 
 
3.2.3.2 
Missing or incomplete dates 
In all listings, missing or incomplete dates should be left as they have been recorded. However, 
for calculation / sorting / assignation based on dates, the following methods will be used: 
• 
The most conservative approach will be systematically considered (i.e., if the onset date 
of an AE/concomitant medication is missing / incomplete, it is assumed to have occurred 
during the study IIP phase (i.e. a TEAE for AEs) except if the partial onset date or other 
data [stop date, …] indicates differently). 
• 
A missing/incomplete date of medical history or disease diagnosis will be assumed to 
have occurred before IIP administration. 
• 
If a partial date and the associated information do not allow to state about the assignation 
to a group / category, all the possible groups / categories will be considered (i.e.: an AE 
could be assigned to several possible doses at event onset according to its partial onset 
date and stop date. Particularly an AE with missing start date will be assigned to each 
dose received before its end date. Similarly, a medication with partial start and stop dates 
could be considered as prior and concomitant treatment). 
• 
Where possible, the derivations based on a partial date will be presented as superior 
inequalities (i.e., for an AE started in FEB2004 after the administration performed on 
31JAN2004, the days since last administration will be “≥2”. Similarly, the duration of 
ongoing AEs or medication will be “≥xx” according to the start and last visit dates).  


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3.2.3.3 
Outliers 
Any outlier identified prior to database lock which is impossible/implausable will be excluded 
from the analysis. For other identified outliers, the impact should be assessed by performing 
the statistical analysis with the actual values and at least one other analysis eliminating or 
reducing the outlier effect. 
If any outliers are identified after database lock the statistical analysis should be performed with 
the actual values and at least one other analysis eliminating or reducing the outlier effect. 
A search of outliers should be performed before the database lock and actions with the sponsor 
should be defined (e.g. edition of queries). 
 
3.2.4 
Subject disposition 
The numbers and percentages of subjects included in each of the Eligibility screened, Safety, 
68Ga-OPS202 screened, sstr2 positive and sstr2 positive evaluable population will be tabulated. 
The reasons for subject exclusions from each of the populations will also be tabulated.  
A listing of dates and time of assessments (relative day) will be presented by subject.  
A summary table will be presented on Safety population presenting the number of subjects at 
each visit and identifying the number of subjects who withdrew from the study over time. A 
unique flow chart will be drawn with the number of subjects in each population.  
The listing of subject disposition will include the subject exposure in the study. The definition 
of the study exposure is defined in the Appendix 1 Derived data. 
 
3.2.5 
Withdrawals 
Discontinued subjects will be listed and a summary table of the number and percentage of 
subjects who completed and withdrew from the study and the reasons for withdrawal will be 
presented. 
 
3.2.6 
Demographic and baseline characteristics 
In order to characterise the subjects, descriptive summary statistics (n, mean, SD, median, 
minimum, and maximum) or frequency counts of demographic and baseline data will be 
presented for the Safety population. 


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Summary statistics will be provided for demographic and baseline characteristics: 
• 
race/ethnicity, age and age class 
• 
height, weight at screening, body mass index (BMI) and BMI in categories at screening 
(refer to Appendix 1, Derived data) 
• 
Eastern Cooperative Oncology Group (ECOG) performance status 
 
Summary statistics of the tumour characteristics will be provided:  
• 
Tumour, node and metastasis (TNM) staging 
• 
presence of metastases 
• 
location of metastases 
• 
Estrogen Receptor status 
• 
Progesterone Receptor status 
• 
IHC result 
• 
ISH result 
 
All demographic and baseline characteristics will be listed by subject. 
Pregnancy tests performed will be listed by subject, and by visit. 
 
3.2.7 
Medical and surgical history 
Medical and surgical history will be coded using MedDRA Version 19.1 or higher. 
Listings will present the preferred term and verbatim text. The listings will be sorted by subject 
number, date of diagnosis, primary SOC, PT and verbatim text.  
A frequency table of the number and percentage of subjects will be provided for all medical 
and surgical history by primary SOC and PT on the safety population. 


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3.2.8 
Subject compliance 
3.2.8.1 
Subject exposure to IIP 
 
Subject exposure to IIP will be described using the safety population presented in a summary 
table for the following data: 
• 
Injection performed (yes/no) 
• 
Injected peptide mass dose (μg) 
• 
Injected radioactivity dose (MBq) 
Computational details for actual injected doses (peptide mass dose and radioactivity dose) are 
available in the Appendix 1 Derived data. 
 
The exposure information will be presented on separate listings as follows: 
 
First subject listing will present the IIP preparation by subject, with following information: 
• 
Date and time of IIP preparation 
• 
Final prepared volume (mL) 
• 
Final prepared dose of radioactivity (MBq) 
• 
IIP prepared as per protocol (yes/no with reason) 
 
Second subject listing will be presented for the IIP administration, by subject, with following 
information: 
• 
Administration performed to the subject (yes/no with reason) 
• 
Date and time of injection 
• 
IIP and batch number 
• 
Volume immediately before administration (mL) 
• 
Radioactivity dose immediately before administration (MBq) 
• 
Left over volume immediately after administration (mL) 
• 
Left over radioactivity dose immediately after administration (MBq) 
• 
Injected peptide mass dose (μg)  
• 
Injected radioactivity dose (MBq)  
 
Moreover, a listing of subjects with extravasation during injection or difficulties during IIP 
administration will be provided. 
 
3.2.8.2 
Protocol deviations 
All the protocol deviations identified will be listed by subject.  
3.2.9 
Prior and concomitant therapies 
Any relevant prior or concomitant therapy or medication given to a subject within 3 months 
before IIP administration, during IIP administration and up to the end of the follow-up period 
will be indicated on the eCRF. Dose and generic name or tradename will be recorded.  


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All recorded data will be included in data listings. 
As defined in study protocol, the following medications/therapies will be considered prohibited 
and will be flagged into listings: 
• 
During the study and up to 48 hours post PET/CT scan: 
- 
Administration of a radiopharmaceutical  
- 
Parenteral amino acid solutions and any formulation of diuretics on Visit 2, 
unless stable adjusted diuretics for subjects with hypertension  
• 
Within 28 days prior to the 68Ga-OPS202 PET/CT exam (Visit 2): 
- 
Long acting SSA, ie, Somatuline® Autogel® /Depot® (60, 90 or 120 mg) and 
Sandostatin® LAR (20 or 30 mg)  
• 
Within 24 hours before the 68Ga-OPS202 PET/CT (Visit 2): 
- 
Short acting SSA (Sandostatin®) 
 
3.2.9.1 
Prior and concomitant medications 
Prior and concomitant medications will be coded using WHO-DD, version June 2016 or higher.  
Medications that started and stopped before study IIP administration are considered as prior 
medications. Medications that started before study IIP administration but are continuing will be 
considered as both prior and concomitant medications. 
Listings will be presented for the therapeutic class, PT and verbatim text. The listings will be 
sorted by subject number, chronological start date, stop date, therapeutic class, PT and verbatim 
text. The therapeutic class will correspond to the second level of ATC code, which corresponds 
to the first three figures. 
A frequency table of the number and percentage of subjects will be provided for prior 
medications and concomitant medications by therapeutic class and PT on the safety population. 
 
3.2.9.2 
Prior and concomitant non-drug therapies 
Prior and concomitant non-drug therapies will be coded using the MedDRA Version 19.1 or 
higher. Therapies which started and stopped before study IIP administration are considered as 
prior non-drug therapies. 
Therapies which started before study IIP administration but are continuing will be considered 
as both prior and concomitant non-drug therapies. 
Listing of prior and concomitant non-drug therapies will be presented for the SOC, PT and 
verbatim text. The listing will be sorted by subject number, chronological start date, stop date, 
SOC, PT and verbatim text.  
A frequency table of the number and percentage of subjects will be provided by SOC and PT 
on the safety population. 
3.2.9.3 
Concomitant medications for breast cancer  
Concomitant medications for breast cancer will be coded using WHO-DD, version June 2016 
or higher. Medications which started and stopped before study IIP administration are considered 
as prior medications for breast cancer. 
Medications which started before study IIP administration but are continuing will be considered 
as both prior and concomitant medications for breast cancer. 


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Listings will be presented for the therapeutic class, PT and verbatim text. The listings will be 
sorted by subject number, chronological start date, stop date, therapeutic class, PT and verbatim 
text.  
A frequency table of the number and percentage of subjects will be provided by therapeutic 
class and PT on the safety population. 
 
3.2.9.4 
Concomitant surgical procedures 
Concomitant surgical procedures will be coded using the MedDRA, Version 19.1 or higher. 
Surgical procedures which started after study IIP administration will be considered as 
concomitant surgical procedures. 
Listings will be presented for the SOC, PT and verbatim text. The listings will be sorted by 
subject number, chronological start date, stop date, SOC, PT and verbatim text.  
A frequency table of the number and percentage of subjects will be provided for concomitant 
surgical procedures by SOC and PT on the safety population. 
 
3.2.10 
Derived data 
The derived data are variables which are calculated from the raw data recorded in the eCRF or 
any other support and not included in the database. The derived data will be calculated to be 
included in tables and listings. Some specifications of the data derivations necessary for this 
study are provided in Appendix 1 Derived Data. 
 
3.2.11 
Rules and data formats 
Data will be presented using an appropriate number of decimal places (i.e. the number of 
decimal places used does not imply undue precision).  Raw data will be presented to the number 
of decimal places collected, and derived data will be presented to an appropriate number of 
decimal places. The appropriate number of decimal places will be determined by general 
practice, mathematical rationale or scientific rationale (e.g. age should be presented in whole 
numbers).  
For summary statistics, the following will be presented n (number of non-missing observations), 
number of missing values (if any), arithmetic mean, standard deviation (SD), median and the 
range (minimum, maximum). 
Mean, median and SD values will be reported to one decimal place greater than the raw/derived 
data that they summarise.  Minimum and maximum values will be reported with the same 
precision as the raw data. 
Percentages will be reported to one decimal place and 0% will not be presented.  Percentages 
will be calculated using a denominator of all subjects in a specified population having non-
missing values. The denominator will be specified in a footnote to the tables for clarification if 
necessary.  
All values below or above a limit of detection (e.g. <0.1 or >100) will be listed as such.   
All text fields must be left justified and numeric or numeric with some text specification (e.g., 
not done, unknown, <4.5) must be decimal justified.  Dates will be presented in the format 
[ddmmmyyyy] and times in the format [hh:mm]. 
 


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3.2.12
Pooling of Centres 
It is not planned to perform a subgroup analysis on individual or groups of centres. 
3.2.13
Interim analysis 
No interim analysis will be performed. One final analysis will be performed at the end of the 
study, after database lock. 
3.2.14
Covariates and analysis of subgroups 
It is not planned to perform such analysis. 
4
COMPUTER SYSTEMS, SOFTWARE AND VALIDATION OF PROGRAMS 
4.1
Hardware 
The statistical analysis will be performed using Windows 7 or newer. 
4.2
Software 
All tables and listings will be produced and statistical analysis performed using SAS® version 
9.2 or higher. All outputs will be in Microsoft Word Format, and delivered by the CRO as one 
single file per tables, listing, figure, and a compilation per ICH section. 
4.3
Validation programs 
SAS® programs are developed to produce clinical study output such as analysis data sets, 
summary tables, data listings or statistical analyses. SOP 
“Programming specifications 
for analysis data sets” provides an overview of the development of such SAS® programs. 
SOP 
 “Verification of statistical programs and output” describes the quality control 
procedures that must be performed for all SAS® programs and outputs. Quality control (QC) 
is defined here as the operational techniques and activities undertaken to verify that the SAS®
programs produce the proper clinical study output by checking for their logic, efficiency and 
commenting, and by inspection of the produced outputs. 
A Program Output Release form 
 will be prepared to document the methods of 
validation.  
Copies of the QC documentation produced as confirmation that the validation process has been 
followed will be provided by Covance Clinical Development SARL and will be retained by the 
sponsor. 
4.4
Restitution of the programs 
All programs (including macros and analysis datasets) producing the tables, listings and 
statistical output along with associated logs will be given to the sponsor when the tables, listings 
and statistical analysis has been finalised. 
CCI
CCI
CCI


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5 
CHANGES FROM PROTOCOL 
 
x Section 3.2:  The SAP Version 2.0 was revised to remove some of the planned analyses 
stated in the study protocol. The decision to remove some of the planned analyses (in 
particular, efficacy endpoints are not summarized in tables) was based upon the limited 
data.  A decision had been made to prematurely terminate this study and at that time, 
there was limited data collected on the study. 
6 
REFERENCES 
 
1 
International Conference on Harmonisation (ICH) E9 Guidance on statistical principles 
for clinical trials. Federal register Vol 63, No. 179 (September 1998). 
 
7 
DATA PRESENTATION 
 
Index and template of Tables and Listings are provided in Appendix 2.