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Clinical Trial Results:
A prospective, Phase 3, multi-center, single-arm, imaging study investigating the safety and diagnostic performance of rhPSMA-7.3 (18F) PET ligand in men with suspected prostate cancer recurrence based on elevated PSA following prior therapy (Spotlight)

Summary
EudraCT number	2019-003382-18
Trial protocol	FI NL
Global end of trial date	12 Oct 2021

Results information
Results version number	v1(current)
This version publication date	31 Dec 2023
First version publication date	31 Dec 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

BED-PSMA-302

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Other trial identifiers

IND Number: 141,561

Sponsor organisation name

Blue Earth Diagnostics, Ireland Ltd

Sponsor organisation address

6th Floor, Grand Canal Square, Dublin, Ireland, Dublin 2

Public contact

PSMA Clinical Manager, Blue Earth Diagnostics, Inc, +1 9199998670, contact@blueearthdx.com

Scientific contact

PSMA Clinical Manager, Blue Earth Diagnostics, Inc, +1 9199998670, contact@blueearthdx.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

12 Oct 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

28 Apr 2021

Global end of trial reached?

Yes

Global end of trial date

12 Oct 2021

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to assess the patient-level correct detection rate (CDR) and region-level positive predictive value (PPV) of rhPSMA-7.3 (18F) positron emission tomography (PET) for biochemical recurrence (BCR) of prostate cancer using histopathology or imaging as a standard of truth (SoT).

Protection of trial subjects

This study was conducted according to the principles of the Declaration of Helsinki and in accordance with the International Council for Harmonisation (ICH) guidelines on Good Clinical Practice (GCP). In addition, all relevant regulations and guidance were followed, including United States (US), European Union (EU) and national legislation. As this study was conducted during the coronavirus disease 2019 (COVID-19) global pandemic, relevant guidance from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) were followed, including, but not limited to, the FDA Guidance for Industry, Investigators, and Institutional Review Boards - Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency (March 2020; updated 30 August 2021) and the EMA Guidance on the Management of Clinical Trials During the COVID-19 (Coronavirus) Pandemic (Version 4, 04 February 2021). Prior to study initiation in each country, the study was authorized by the relevant Regulatory Agency/Competent Authority. All applicable privacy regulations (e.g. US Health Insurance Portability and Accountability Act [HIPAA] 1996; EU General Data Protection Regulation [GDPR] 2018; United Kingdom [UK] Data Protection Act 2018) were adhered to.

Background therapy

None

Evidence for comparator

None

Actual start date of recruitment

04 May 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 9

Country: Number of subjects enrolled

Finland: 7

Country: Number of subjects enrolled

United States: 375

Worldwide total number of subjects

391

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

121

From 65 to 84 years

267

85 years and over

Subject disposition

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Recruitment details

This study was conducted from 04 May 20 (first patient, screening visit) and 12 Oct 21 (database lock), with last patient, last visit on 28 Apr 21. It was conducted at 28 activated study sites (27 recruited) in 3 countries. Of the 420 patients screened, 391 patients met all the study eligibility criteria

Screening details

Baseline safety evaluations performed at screening (Visit 1) comprised vital signs and recording of any adverse events (AEs) from the time of informed consent.

Period 1 title

Full Analysis Set (FAS) (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Not relevant

Single Arm

Arm description

All patients who were scheduled to receive the rhPSMA-7.3 (18F) injection having met the inclusion/exclusion criteria or who received the rhPSMA-7.3 (18F) injection.

Arm type

Experimental

Investigational medicinal product name

rhPSMA-7.3 (18F)

Investigational medicinal product code

rhPSMA-7.3 (18F)

Other name

flotufolastat F18

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

All patients were planned to receive a single dose of IMP, with an administered activity of 8 mCi (296 MBq) ± 20% of rhPSMA-7.3 (18F), delivered as an IV bolus injection followed by a 10 mL fast 0.9% sodium chloride flush. The mass dose administered was less than 100 µg/patient. rhPSMA-7.3 (18F) was supplied as a sterile, aqueous solution for IV administration either in a multi-dose vial sealed with a synthetic rubber closure and aluminum overseal or in a single unit dose syringe depending on the manufacturing location

Number of subjects in period 1	Single Arm
Started	391
Completed	391

Baseline characteristics

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Reporting group title

Full Analysis Set (FAS)

Reporting group description

All patients who were scheduled to receive the rhPSMA-7.3 (18F) injection having met the inclusion/exclusion criteria or who received the rhPSMA-7.3 (18F) injection.

Reporting group values	Full Analysis Set (FAS)	Total
Number of subjects	391	391
Age categorical
Age in years
Units: Subjects
< 65	121	121
≥ 65	270	270
Age continuous
Age in years
Units: years
arithmetic mean (standard deviation)	68.3 ( 7.92 )	-
Gender categorical
Gender as Male or Female
Units: Subjects
Female	0	0
Male	391	391
Race
Race split into 3 substantive categories and also those for whom it was not reported
Units: Subjects
Black or African American	61	61
White	295	295
Other	14	14
Not Reported	21	21
Ethnicity
Ethnicity split into 2 substantive groups and those for whom it was not reported
Units: Subjects
Hispanic or Latino	18	18
Non-Hispanic or Latino	342	342
Not Reported	31	31
Total Gleason Score
Gleason score (defined by the International Society of Urological Pathologists) was based on prostate biopsy.
Units: Subjects
≤6	39	39
=7	232	232
=8	41	41
=9	63	63
=10	1	1
Missing	15	15
Gleason Grade Group (GGG)
GGG (defined by the International Society of Urological Pathologists) was based on prostate biopsy.
Units: Subjects
=1	39	39
=2	104	104
=3	116	116
=4	41	41
=5	64	64
Missing	27	27
TNM (Tumor-Node-Metastasis) Stage T
Pathological TNM stage was used if available, otherwise the clinical TNM was used.
Units: Subjects
T1	4	4
T1c	54	54
T2	52	52
T2a	15	15
T2b	10	10
T2c	63	63
T3	10	10
T3a	82	82
T3b	68	68
T3c	0	0
T4	2	2
TX	7	7
Missing	24	24
TNM Stage N
Pathological TNM stage was used if available, otherwise the clinical TNM was used.
Units: Subjects
N0	249	249
N1	53	53
NX	61	61
Missing	28	28
TNM Stage M
Pathological TNM stage was used if available, otherwise the clinical TNM was used.
Units: Subjects
M0	243	243
M1	1	1
M1a	0	0
M1b	1	1
M1c	0	0
MX	106	106
Missing	40	40
Body Mass Index (BMI)
BMI was calculated as weight in kg divided by height in m2.
Units: Kg/m2
arithmetic mean (standard deviation)	28.68 ( 4.740 )	-
Time since initial cancer diagnosis
<<Time in months.>>
Units: Months
arithmetic mean (standard deviation)	87.3 ( 65.70 )	-
Time since diagnosis of biochemical recurrence
Time since diagnosis of biochemical recurrence
Units: Month
geometric mean (standard deviation)	17.1 ( 27.15 )	-
Time since start of adjuvant treatment
Time since start of adjuvant treatment.
Units: month
geometric mean (standard deviation)	67.3 ( 50.26 )	-
Time since end of adjuvant treatment
Time since end of adjuvant treatment.
Units: month
geometric mean (standard deviation)	60.2 ( 49.11 )	-
Duration of adjuvant treatment
Duration of adjuvant treatment.
Units: month
geometric mean (standard deviation)	7.2 ( 16.05 )	-

End points

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Reporting group title

Single Arm

Reporting group description

All patients who were scheduled to receive the rhPSMA-7.3 (18F) injection having met the inclusion/exclusion criteria or who received the rhPSMA-7.3 (18F) injection.

Subject analysis set title

Efficacy Analysis Population

Subject analysis set type

Full analysis

Subject analysis set description

All patients who were scheduled to receive the rhPSMA-7.3 (18F) injection having met the inclusion/exclusion criteria or who received the rhPSMA-7.3 (18F) injection.

Primary: Patient-Level CDR Reader 1

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End point title

Patient-Level CDR Reader 1

End point description

Patient-level CDR was defined as the percentage of all patients scanned who had at least one TP lesion (localized correspondence between rhPSMA-7.3 (18F) PET imaging and the reference standard) regardless of any co-existing FP findings. To determine patient-level CDR, images were interpreted by 3 independent central PET readers. 3 different central readers (SoT consensus panel) then reviewed all available conventional images (historical, baseline and confirmatory imaging scans) and determined via consensus if representative rhPSMA-7.3 (18F) PET-positive lesions identified by the central PET readers were consistent with prostate cancer (SoT proven; True Positive [TP] lesions) or not consistent with prostate cancer (SoT not proven: False Positive [FP] lesions). These consensus reads of the confirmatory imaging for SoT assessment were directed by rhPSMA-7.3 (18F) PET findings.

End point type

Primary

End point timeframe

In the 60 days post-PET scan, patients were to undergo an image-guided confirmatory biopsy or confirmatory conventional imaging of any PET-positive lesion(s) for SoT assessment.

End point values	Single Arm	Efficacy Analysis Population
Number of subjects analysed	366	366
Units: Percentage
number (confidence interval 95%)	54.1 (48.8 to 59.3)	54.1 (48.8 to 59.3)

Patient Level CDR - Reader 1

Statistical analysis description

The co-primary endpoint of patient-level CDR of rhPSMA-7.3 (18F) PET. The hypothesis was H0: CDR ≤36.5% versus H1: CDR >36.5%.

Comparison groups

Single Arm v Efficacy Analysis Population

Number of subjects included in analysis

732

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

< 0.001 ^[2]

Method

Exact binomial

Parameter type

Percentage

Point estimate

54.1

Confidence interval

level

95%

sides

2-sided

lower limit

48.8

upper limit

59.3

Variability estimate

Standard deviation

Notes
[1] - The endpoint was summarized as a percentage, together with a 2-sided exact 95% confidence interval (CI) for each of the three independent central PET readers. In addition, a 1-sided exact binomial test p-value was provided for each independent central PET reader for the CDR.
[2] - H0: CDR ≤ 36.5%

Primary: Patient-Level CDR Reader 2

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End point title

Patient-Level CDR Reader 2

End point description

Region-level PPV was defined as TP/[TP+FP], using all PET-positive regions) of rhPSMA-7.3 (18F) PET. 3 different central readers (SoT consensus panel) then reviewed all available conventional images (historical, baseline and confirmatory imaging scans) and determined via consensus if representative rhPSMA-7.3 (18F) PET-positive lesions identified by the central PET readers were consistent with prostate cancer (SoT proven; True Positive [TP] lesions) or not consistent with prostate cancer (SoT not proven: False Positive [FP] lesions). These consensus reads of the confirmatory imaging for SoT assessment were directed by rhPSMA-7.3 (18F). PET findings. PET positive lesions, as determined by the blinded, central read, will be subjected to the SoT algorithm to determine the patient level CDR and region level PPV.

End point type

Primary

End point timeframe

In the 60 days post-PET scan, patients were to undergo an image-guided confirmatory biopsy or confirmatory conventional imaging of any PET-positive lesion(s) for SoT assessment.

End point values	Single Arm	Efficacy Analysis Population
Number of subjects analysed	366	366
Units: Percentage
number (confidence interval 95%)	51.4 (46.1 to 56.6)	51.4 (46.1 to 56.6)

Patient-Level CDR Reader 2

Statistical analysis description

The co-primary endpoint of patient-level CDR of rhPSMA-7.3 (18F) PET. The hypothesis was H0: CDR ≤36.5% versus H1: CDR >36.5%.

Comparison groups

Single Arm v Efficacy Analysis Population

Number of subjects included in analysis

732

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

< 0.0001 ^[4]

Method

Exact binomial test

Parameter type

Percentage

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

46.1

upper limit

56.6

Variability estimate

Standard deviation

Notes
[3] - The endpoint was summarized as a percentage, together with a 2-sided exact 95% confidence interval (CI) for each of the three independent central PET readers. In addition, a 1-sided exact binomial test p-value was provided for each independent central PET reader for the CDR.
[4] - H0: CDR ≤ 36.5%

Primary: Patient-Level CDR Reader 3

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End point title

Patient-Level CDR Reader 3

End point description

Patient-level CDR was defined as the percentage of all patients scanned who had at least one TP lesion (localized correspondence between rhPSMA-7.3 (18F) PET imaging and the reference standard) regardless of any co-existing FP findings. To determine patient-level CDR images were interpreted by 3 independent central PET readers. 3 different central readers (SoT consensus panel) then reviewed all available conventional images (historical, baseline and confirmatory imaging scans) and determined via consensus if representative rhPSMA-7.3 (18F) PET-positive lesions identified by the central PET readers were consistent with prostate cancer (SoT proven; True Positive [TP] lesions) or not consistent with prostate cancer (SoT not proven: False Positive [FP] lesions). These consensus reads of the confirmatory imaging for SoT assessment were directed by rhPSMA-7.3 (18F) PET findings.

End point type

Primary

End point timeframe

In the 60 days post-PET scan, patients were to undergo an image-guided confirmatory biopsy or confirmatory conventional imaging of any PET-positive lesion(s) for SoT assessment.

End point values	Single Arm	Efficacy Analysis Population
Number of subjects analysed	366	366
Units: percentage
number (confidence interval 95%)	51.6 (46.4 to 56.9)	51.6 (46.4 to 56.9)

Patient-Level CDR Reader 3

Statistical analysis description

The co-primary endpoint of patient-level CDR of rhPSMA-7.3 (18F) PET. The hypothesis was H0: CDR ≤36.5% versus H1: CDR >36.5%.

Comparison groups

Single Arm v Efficacy Analysis Population

Number of subjects included in analysis

732

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

< 0.0001 ^[6]

Method

Exact binomial

Parameter type

Percentage

Point estimate

51.6

Confidence interval

level

95%

sides

2-sided

lower limit

46.4

upper limit

56.9

Variability estimate

Standard deviation

Notes
[5] - The endpoint was summarized as a percentage, together with a 2-sided exact 95% confidence interval (CI) for each of the 3 independent central PET readers. In addition, a 1-sided exact binomial test p-value was provided for each independent central PET reader for the CDR.
[6] - H0: CDR ≤ 36.5%

Primary: Region-level PPV Reader 1

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End point title

Region-level PPV Reader 1

End point description

Region-level PPV was defined as TP/[TP+FP], using all PET-positive regions) of rhPSMA-7.3 (18F) PET. 3 different central readers (SoT consensus panel) then reviewed all available conventional images (historical, baseline and confirmatory imaging scans) and determined via consensus if representative rhPSMA-7.3 (18F) PET-positive lesions identified by the central PET readers were consistent with prostate cancer (SoT proven; True Positive [TP] lesions) or not consistent with prostate cancer (SoT not proven: False Positive [FP] lesions). These consensus reads of the confirmatory imaging for SoT assessment were directed by rhPSMA-7.3 (18F) PET findings. PET positive lesions, as determined by the blinded, central read, will be subjected to the SoT algorithm to determine the patient level CDR and region level PPV.

End point type

Primary

End point timeframe

In the 60 days post-PET scan, patients were to undergo an image-guided confirmatory biopsy or confirmatory conventional imaging of any PET-positive lesion(s) for SoT assessment.

End point values	Single Arm	Efficacy Analysis Population
Number of subjects analysed	366	366
Units: percentage
number (confidence interval 95%)	46.2 (42.0 to 50.3)	46.2 (42.0 to 50.3)

Region-level PPV Reader 1

Statistical analysis description

The co-primary endpoint of region-level PPV of rhPSMA-7.3 (18F) PET. The hypothesis was H0: PPV ≤62.5% versus H1: PPV >62.5%.

Comparison groups

Single Arm v Efficacy Analysis Population

Number of subjects included in analysis

732

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

= 1 ^[8]

Method

Exact binomial

Parameter type

Percentage

Point estimate

46.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

50.3

Variability estimate

Standard deviation

Notes
[7] - The endpoint was summarized as a percentage, together with a 2-sided exact 95% confidence interval (CI) for each of the three independent central PET readers. In addition, a 1-sided exact binomial test p-value was provided for each independent central PET reader for the PPV.
[8] - H0: PPV ≤ 62.5%

Primary: Region-level PPV Reader 2

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End point title

Region-level PPV Reader 2

End point description

Region-level PPV was defined as TP/[TP+FP], using all PET-positive regions) of rhPSMA-7.3 (18F) PET. 3 different central readers (SoT consensus panel) then reviewed all available conventional images (historical, baseline and confirmatory imaging scans) and determined via consensus if representative rhPSMA-7.3 (18F) PET-positive lesions identified by the central PET readers were consistent with prostate cancer (SoT proven; True Positive [TP] lesions) or not consistent with prostate cancer (SoT not proven: False Positive [FP] lesions). These consensus reads of the confirmatory imaging for SoT assessment were directed by rhPSMA-7.3 (18F) PET findings. PET positive lesions, as determined by the blinded, central read, will be subjected to the SoT algorithm to determine the patient level CDR and region level PPV.

End point type

Primary

End point timeframe

In the 60 days post-PET scan, patients were to undergo an image-guided confirmatory biopsy or confirmatory conventional imaging of any PET-positive lesion(s) for SoT assessment.

End point values	Single Arm	Efficacy Analysis Population
Number of subjects analysed	366	366
Units: percentage
number (confidence interval 95%)	60.3 (55.1 to 65.5)	60.3 (55.1 to 65.5)

Region-level PPV Reader 2

Statistical analysis description

The co-primary endpoint of region-level PPV of rhPSMA-7.3 (18F) PET. The hypothesis was H0: PPV ≤62.5% versus H1: PPV >62.5%.

Comparison groups

Single Arm v Efficacy Analysis Population

Number of subjects included in analysis

732

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.7954 ^[10]

Method

Exact binomial

Parameter type

Percentage

Point estimate

60.3

Confidence interval

level

95%

sides

2-sided

lower limit

55.1

upper limit

65.5

Notes
[9] - The endpoint was summarized as a percentage, together with a 2-sided exact 95% confidence interval (CI) for each of the three independent central PET readers. In addition, a 1-sided exact binomial test p-value was provided for each independent central PET reader for the PPV.
[10] - H0 PPV ≤ 62.5%

Primary: Region-level PPV Reader 3

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End point title

Region-level PPV Reader 3

End point description

Region-level PPV was defined as TP/[TP+FP], using all PET-positive regions) of rhPSMA-7.3 (18F) PET. 3 different central readers (SoT consensus panel) then reviewed all available conventional images (historical, baseline and confirmatory imaging scans) and determined via consensus if representative rhPSMA-7.3 (18F) PET-positive lesions identified by the central PET readers were consistent with prostate cancer (SoT proven; True Positive [TP] lesions) or not consistent with prostate cancer (SoT not proven: False Positive [FP] lesions). These consensus reads of the confirmatory imaging for SoT assessment were directed by rhPSMA-7.3 (18F) PET findings. PET positive lesions, as determined by the blinded, central read, will be subjected to the SoT algorithm to determine the patient level CDR and region level PPV.

End point type

Primary

End point timeframe

In the 60 days post-PET scan, patients were to undergo an image-guided confirmatory biopsy or confirmatory conventional imaging of any PET-positive lesion(s) for SoT assessment.

End point values	Single Arm	Efficacy Analysis Population
Number of subjects analysed	366	366
Units: percentage
number (confidence interval 95%)	52.6 (47.6 to 57.5)	52.6 (47.6 to 57.5)

Region Level PPV Reader 3

Statistical analysis description

The co-primary endpoint of region-level PPV of rhPSMA-7.3 (18F) PET. The hypothesis was H0: PPV ≤62.5% versus H1: PPV >62.5%.

Comparison groups

Single Arm v Efficacy Analysis Population

Number of subjects included in analysis

732

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

= 1 ^[12]

Method

Exact binomial

Parameter type

Percentage

Point estimate

52.6

Confidence interval

level

95%

sides

2-sided

lower limit

47.6

upper limit

57.5

Notes
[11] - The endpoint was summarized as a percentage, together with a 2-sided exact 95% confidence interval (CI) for each of the three independent central PET readers. In addition, a 1-sided exact binomial test p-value was provided for each independent central PET reader for the PPV.
[12] - H0 PPV ≤ 62.5%

Adverse events

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Timeframe for reporting adverse events

AEs were also monitored throughout the study from the time of informed consent until the last study visit.

Adverse event reporting additional description

AEs (treatment emergent) were coded with MedDRA and data listed by patient: study site, patient identifier, age, race, AE (MedDRA SOC, PT and verbatim term), dates of onset and resolution, duration, CTCAE toxicity grade, seriousness, action taken, outcome and causality. Deaths, SAEs and AEs leading to discontinuation were listed by patient

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Full Safety Population (FSP)

Reporting group description

<<All patients who received the rhPSMA-7.3 (18F) injection.>>

Serious adverse events	Full Safety Population (FSP)
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 391 (0.51%)
number of deaths (all causes)	2
number of deaths resulting from adverse events	1
General disorders and administration site conditions
Sudden death
subjects affected / exposed	1 / 391 (0.26%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	1 / 1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	1 / 391 (0.26%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Full Safety Population (FSP)
Total subjects affected by non serious adverse events
subjects affected / exposed	28 / 391 (7.16%)
Vascular disorders
Hypertension
subjects affected / exposed	7 / 391 (1.79%)
occurrences all number	7
Flushing
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
General disorders and administration site conditions
Injection site reaction
subjects affected / exposed	2 / 391 (0.51%)
occurrences all number	2
Injection site discomfort
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Fatigue
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Respiratory, thoracic and mediastinal disorders
Sinus congestion
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Pulmonary embolism
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Injury, poisoning and procedural complications
Post procedural haemorrhage
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Cardiac disorders
Tachycardia
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Nervous system disorders
Headache
subjects affected / exposed	2 / 391 (0.51%)
occurrences all number	2
Paraesthesia
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Dizziness
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Eye disorders
Vision blurred
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	4 / 391 (1.02%)
occurrences all number	4
Abdominal pain
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Nausea
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Renal and urinary disorders
Ureterolithiasis
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Musculoskeletal and connective tissue disorders
Flank pain
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Musculoskeletal chest pain
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	1 / 391 (0.26%)
occurrences all number	1

More information

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Were there any global substantial amendments to the protocol? Yes

07 Jan 2020

Updates based on feedback from the US FDA, including amendment of the co-primary efficacy endpoint. Clarify: definition for the co-primary endpoint of CDR. Update: co-primary endpoint of PPV; changed to a region-level not patient-level analysis (FDA recommended). Details added on how this was determined. Add: text to indicate the overall PPV will likely be decreased by patients with multiple PSMA PET-positive regions given histological confirmation of multiple lesions in the same patient is highly unlikely. Edits: secondary and exploratory endpoints for clarity. Add: details to stop enrollment of patients with a PSA <1 ng/mL if the proportion exceeds 60% at the planned interim analysis. Add: Optional Visit 2a. Clarify: dose of IMP could be 8 mCi (296 MBq) ± 20% of rhPSMA-7.3 (18F). Clarify: key assumptions. Edit: inclusion criteria regarding elevated PSA, clinically suspicious for biochemically recurrent disease to include nadir +2 ng/mL following focal gland therapies. Update: diluted volumes of IMP that can be used and to the shelf life of IMP. Clarify: wording around baseline conventional imaging, historical conventional imaging and addition of text for confirmatory imaging. Edit: process for biopsy/surgery, SoT algorithm and central reading plan. Clarify: assessment of impact on clinical management plan depends on clinical utility questionnaire completed pre- and post-PSMA PET scan. Clarify: timepoint for conventional imaging if historical conventional imaging took place greater than 90 days before Visit 1. Update: sample size and number of evaluable patients required before enrollment will stop. Update: analysis sets. Add: detail for the joint hypothesis for the co-primary endpoints. Add: planned interim analysis once 60% of the planned 190 positive cases have information. Minor typographical edits.

01 Jul 2020

Updates to ensure patient safety for COVID-19/implement BfArM feedback Screening extended 28-45 days Add: Visit 1 and Visit 2 combined Clarify: conventional imaging at non-participating institutions acceptable Clarifiy: patients with multiple PET-positive regions, confirmed at least 1 PET-positive lesion in each region needed for efficacy analyses Add: possible to delay biopsy and surgical procedures performed to obtain SoT histopathology and initial confirming imaging up to Day 60 for safety Clarify: inclusion criterion related to elevated PSA, clinically suspicious for biochemically recurrent disease Add: exclusion criterion: patients with hypersensitivity to the active substance or any of the IMP excipients Clarifiy: contrast-enhanced CT/MRI and radiopharmaceutical-based baseline conventional imaging performed at least 24 hours apart from investigational rhPSMA-7.3 (18F) PET scan Define: regions added: prostate bed, pelvic lymph nodes, and other Add: assessment of the most accessible and feasible lesion(s) for biopsy include safety consideration, and others already listed Clarify: patients with multiple lesions in a specific region, 1 TP lesion determines region truth regardless of concurrent FP findings in same region Increase from 2-3 independent central PET readers for the rhPSMA-7.3 (18F) PET scans and details of information provided added (Independent Review Charter) Add: Visit 3 could be performed by a licensed and credentialed clinician and conducted by telephone per site discretion Add: text on the replacement of dropout patients Update: SAE reporting email address; clarify: SAEs to be reported immediately Add: section detailing reasons patient enrollment may be temporarily halted/stopped Add: option for remote study monitoring instead of on-site monitoring (COVID-19) Clarify: Urgent Safety Measures include amendments made due to COVID-19 to ensure safety by minimizing potential exposure to SARS-CoV-2 Minor typographical edits

23 Oct 2020

Removal of the formal (hypothesis testing) interim analysis. Remove: the following exploratory objective and corresponding endpoint: assess an incremental rhPSMA-7.3 (18F) PET findings (e.g. more sites of involvement) compared to conventional imaging. Add: BMI to demographic information recorded at screening. Update: SAE reporting email address and medical monitor details. Minor typographical edits.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None

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Clinical trials

Clinical Trial Results:
A prospective, Phase 3, multi-center, single-arm, imaging study investigating the safety and diagnostic performance of rhPSMA-7.3 (18F) PET ligand in men with suspected prostate cancer recurrence based on elevated PSA following prior therapy (Spotlight)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Patient-Level CDR Reader 1

Primary: Patient-Level CDR Reader 1

Primary: Patient-Level CDR Reader 2

Primary: Patient-Level CDR Reader 2

Primary: Patient-Level CDR Reader 3

Primary: Patient-Level CDR Reader 3

Primary: Region-level PPV Reader 1

Primary: Region-level PPV Reader 1

Primary: Region-level PPV Reader 2

Primary: Region-level PPV Reader 2

Primary: Region-level PPV Reader 3

Primary: Region-level PPV Reader 3

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: A prospective, Phase 3, multi-center, single-arm, imaging study investigating the safety and diagnostic performance of rhPSMA-7.3 (18F) PET ligand in men with suspected prostate cancer recurrence based on elevated PSA following prior therapy (Spotlight)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Patient-Level CDR Reader 1

Primary: Patient-Level CDR Reader 1

Primary: Patient-Level CDR Reader 2

Primary: Patient-Level CDR Reader 2

Primary: Patient-Level CDR Reader 3

Primary: Patient-Level CDR Reader 3

Primary: Region-level PPV Reader 1

Primary: Region-level PPV Reader 1

Primary: Region-level PPV Reader 2

Primary: Region-level PPV Reader 2

Primary: Region-level PPV Reader 3

Primary: Region-level PPV Reader 3

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A prospective, Phase 3, multi-center, single-arm, imaging study investigating the safety and diagnostic performance of rhPSMA-7.3 (18F) PET ligand in men with suspected prostate cancer recurrence based on elevated PSA following prior therapy (Spotlight)