Trial Outcomes & Findings for Open-label PET Study With [11C]Osimertinib in Patients With EGFRm NSCLC and Brain Metastases (NCT NCT03463525)
NCT ID: NCT03463525
Last Updated: 2023-01-27
Results Overview
During the PET examination time, a series of arterial blood samples were taken to measure Cmax, %ID brain of \[11C\]osimertinib.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
4 participants
Primary outcome timeframe
Day 1, Day 2 (or up to Day 8) and Day 25
Results posted on
2023-01-27
Participant Flow
This Phase 1 study was conducted in participants with epidermal growth factor receptor mutation positive non-small cell lung cancer with brain metastases at a single center in Sweden.
The study consisted of 2 phases, an Imaging Phase and a Continued Access Phase. A total of 4 participants were enrolled in this study. All 4 participants received treatment and completed the study.
Participant milestones
| Measure |
All Participants
Participants received \[11C\]osimertinib intravenous (IV) microdose (\< 10 microgram \[μg\]) with radioactivity of 300 megabecquerel (MBq)/70 kilogram (kg) of body weight prior to positron emission tomography (PET) examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 milligram (mg) oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Overall Study
STARTED
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4
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Overall Study
COMPLETED
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4
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Open-label PET Study With [11C]Osimertinib in Patients With EGFRm NSCLC and Brain Metastases
Baseline characteristics by cohort
| Measure |
All Participants
n=4 Participants
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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2 Participants
n=5 Participants
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Age, Categorical
>=65 years
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2 Participants
n=5 Participants
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Sex: Female, Male
Female
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2 Participants
n=5 Participants
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Sex: Female, Male
Male
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2 Participants
n=5 Participants
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Race/Ethnicity, Customized
Not Hispanic or Latino
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4 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Day 1, Day 2 (or up to Day 8) and Day 25Population: The PET analysis set included all participants who completed at least one PET examination for the evaluation of \[11C\]osimertinib brain distribution.
During the PET examination time, a series of arterial blood samples were taken to measure Cmax, %ID brain of \[11C\]osimertinib.
Outcome measures
| Measure |
All Participants
n=4 Participants
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Maximum Concentration of Percent of Injected Dose in the Whole Brain (Cmax, %ID Brain) of [11C]Osimertinib
Day 1: PET1
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1.465 percent of radioactive drug
Geometric Coefficient of Variation 9.6
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Maximum Concentration of Percent of Injected Dose in the Whole Brain (Cmax, %ID Brain) of [11C]Osimertinib
Day 2 (or up to Day 8): PET2
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1.617 percent of radioactive drug
Geometric Coefficient of Variation 6.6
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Maximum Concentration of Percent of Injected Dose in the Whole Brain (Cmax, %ID Brain) of [11C]Osimertinib
Day 25: PET3
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1.492 percent of radioactive drug
Geometric Coefficient of Variation 15.1
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PRIMARY outcome
Timeframe: Day 1, Day 2 (or up to Day 8) and Day 25Population: The PET analysis set included all participants who completed at least one PET examination for the evaluation of \[11C\]osimertinib brain distribution.
During the PET examination time, a series of arterial blood samples were taken to measure Cmax, SUV brain of \[11C\]osimertinib.
Outcome measures
| Measure |
All Participants
n=4 Participants
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Maximum Concentration of Brain Standardized Uptake Value (Cmax, SUV Brain) of [11C]Osimertinib
Day 1: PET1
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1.006 SUV
Geometric Coefficient of Variation 27.1
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Maximum Concentration of Brain Standardized Uptake Value (Cmax, SUV Brain) of [11C]Osimertinib
Day 2 (or up to Day 8): PET2
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1.111 SUV
Geometric Coefficient of Variation 22.0
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Maximum Concentration of Brain Standardized Uptake Value (Cmax, SUV Brain) of [11C]Osimertinib
Day 25: PET3
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1.054 SUV
Geometric Coefficient of Variation 29.1
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PRIMARY outcome
Timeframe: Day 1, Day 2 (or up to Day 8) and Day 25Population: The PET analysis set included all participants who completed at least one PET examination for the evaluation of \[11C\]osimertinib brain distribution.
The Tmax, brain was determined directly from the observed concentration versus time data.
Outcome measures
| Measure |
All Participants
n=4 Participants
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Time of Maximum Radioactivity Concentration in the Brain (Tmax, Brain) of [11C]Osimertinib
Day 1: PET1
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22.160 minutes
Interval 10.67 to 42.23
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Time of Maximum Radioactivity Concentration in the Brain (Tmax, Brain) of [11C]Osimertinib
Day 2 (or up to Day 8): PET2
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36.340 minutes
Interval 8.83 to 78.25
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Time of Maximum Radioactivity Concentration in the Brain (Tmax, Brain) of [11C]Osimertinib
Day 25: PET3
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37.125 minutes
Interval 16.83 to 60.3
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PRIMARY outcome
Timeframe: Day 1, Day 2 (or up to Day 8) and Day 25Population: The PET analysis set included all participants who completed at least one PET examination for the evaluation of \[11C\]osimertinib brain distribution.
The Kp was defined as ratio of radiolabeled drug in brain to that in plasma calculated as area under the brain radioactivity concentration-time curve between 0 and 90 minutes/area under the plasma radioactivity concentration-time curve between 0 and 90 minutes.
Outcome measures
| Measure |
All Participants
n=4 Participants
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Brain to Plasma Partition Coefficient (Kp) of [11C]Osimertinib
Day 1: PET1
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3.753 ratio
Standard Deviation 0.8328
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Brain to Plasma Partition Coefficient (Kp) of [11C]Osimertinib
Day 2 (or up to Day 8): PET2
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3.960 ratio
Standard Deviation 0.9413
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Brain to Plasma Partition Coefficient (Kp) of [11C]Osimertinib
Day 25: PET3
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4.658 ratio
Standard Deviation 1.5362
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SECONDARY outcome
Timeframe: Pre-dose and 2, 4 and 7.5 hours postdose on Day 25Population: The Pharmacokinetic (PK) analysis set included all participants who received at least one administration of either \[11C\]osimertinib and/or osimertinib and had postadministration PK assessments of osimertinib and/or its metabolite AZ5104 without any protocol deviations or administration deviations that could have affected the PK analysis.
Venous blood samples were collected to determine Css,max of osimertinib and metabolite AZ5104.
Outcome measures
| Measure |
All Participants
n=4 Participants
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Maximum Concentration at Steady State (Css,Max) of Osimertinib and Metabolite AZ5104
Osimertinib
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648.0 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 29.61
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Maximum Concentration at Steady State (Css,Max) of Osimertinib and Metabolite AZ5104
Metabolite AZ5104
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76.53 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 59.58
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SECONDARY outcome
Timeframe: Pre-dose and 2, 4 and 7.5 hours postdose on Day 25Population: The PK analysis set included all participants who received at least one administration of either \[11C\]osimertinib and/or osimertinib and had postadministration PK assessments of osimertinib and/or its metabolite AZ5104 without any protocol deviations or administration deviations that could have affected the PK analysis.
Venous blood samples were collected to determine tss,max of osimertinib and metabolite AZ5104.
Outcome measures
| Measure |
All Participants
n=4 Participants
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Time of Maximum Drug Concentration at Steady State (Tss,Max) of Osimertinib and Metabolite AZ5104
Osimertinib
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4.0 hours (h)
Interval 4.0 to 6.0
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Time of Maximum Drug Concentration at Steady State (Tss,Max) of Osimertinib and Metabolite AZ5104
Metabolite AZ5104
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4.0 hours (h)
Interval 0.0 to 6.0
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SECONDARY outcome
Timeframe: Pre-dose and 2, 4 and 7.5 hours postdose on Day 25Population: The PK analysis set included all participants who received at least one administration of either \[11C\]osimertinib and/or osimertinib and had postadministration PK assessments of osimertinib and/or its metabolite AZ5104 without any protocol deviations or administration deviations that could have affected the PK analysis.
Venous blood samples were collected to determine AUCss of osimertinib and metabolite AZ5104.
Outcome measures
| Measure |
All Participants
n=4 Participants
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Area Under the Concentration-Time Curve at Steady State (AUCss) of Osimertinib and Metabolite AZ5104
Osimertinib
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13080 h*nmol/L
Geometric Coefficient of Variation 32.70
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Area Under the Concentration-Time Curve at Steady State (AUCss) of Osimertinib and Metabolite AZ5104
Metabolite AZ5104
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1666 h*nmol/L
Geometric Coefficient of Variation 64.12
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SECONDARY outcome
Timeframe: Pre-dose and 2, 4 and 7.5 hours postdose on Day 25Population: The PK analysis set included all participants who received at least one administration of either \[11C\]osimertinib and/or osimertinib and had postadministration PK assessments of osimertinib and/or its metabolite AZ5104 without any protocol deviations or administration deviations that could have affected the PK analysis.
Venous blood samples were collected to determine AUCss of osimertinib and metabolite AZ5104.
Outcome measures
| Measure |
All Participants
n=4 Participants
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Metabolite to Parent Ratio of AUCss
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0.1274 ratio
Geometric Coefficient of Variation 27.89
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SECONDARY outcome
Timeframe: Pre-dose and 2, 4 and 7.5 hours postdose on Day 25Population: The PK analysis set included all participants who received at least one administration of either \[11C\]osimertinib and/or osimertinib and had postadministration PK assessments of osimertinib and/or its metabolite AZ5104 without any protocol deviations or administration deviations that could have affected the PK analysis.
Venous blood samples were collected to determine Css,max of osimertinib and metabolite AZ5104.
Outcome measures
| Measure |
All Participants
n=4 Participants
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Metabolite to Parent Ratio of Css,Max
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0.1181 ratio
Geometric Coefficient of Variation 28.91
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Adverse Events
All Participants
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
All Participants
n=4 participants at risk
Participants received \[11C\]osimertinib IV microdose (\< 10 μg) with radioactivity of 300 MBq/70 kg of body weight prior to PET examinations on Day 1, Day 2 (or up to Day 8), and Day 25 (±4 days). The minimum injected radioactivity was 200 MBq/70 kg and the maximum was 330 MBq/70 kg of body weight. Additionally, participants received osimertinib 80 mg oral tablets once daily from the day of the second PET examination for at least 21 days till the third PET examination.
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Psychiatric disorders
Anxiety
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Cardiac disorders
Sinus tachycardia
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Gastrointestinal disorders
Diarrhoea
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Gastrointestinal disorders
Nausea
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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General disorders
Chest pain
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Infections and infestations
Oral candidiasis
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Infections and infestations
Urinary tract infection
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Injury, poisoning and procedural complications
Procedural pain
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Injury, poisoning and procedural complications
Skin wound
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Musculoskeletal and connective tissue disorders
Pain in extremity
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Nervous system disorders
Dysgeusia
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Nervous system disorders
Headache
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Nervous system disorders
Taste disorder
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25.0%
1/4 • Number of events 2 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Respiratory, thoracic and mediastinal disorders
Dyspnoea
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Skin and subcutaneous tissue disorders
Dry skin
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50.0%
2/4 • Number of events 2 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Skin and subcutaneous tissue disorders
Rash
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Skin and subcutaneous tissue disorders
Skin oedema
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Vascular disorders
Haematoma
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25.0%
1/4 • Number of events 1 • Adverse events were collected from the first dose administration of study drug (Day 1) up to 30 days after last dose administration of study drug, approximately 55 days.
The safety analysis set included all participants who received at least one administration of \[11C\]osimertinib and/or osimertinib.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place