Phase 1 Study of 64Cu-DOTA-Patritumab
Page 1 (Version 10.0 9-2-15)
Supplemental Material
Supplemental Table 1: Eligibility criteria.
Exclusion
Inclusion
1. Pathologically confirmed advanced solid
1. Liver, spleen, or both as the only sites of
tumor, refractory to standard treatment or for
disease.
which no standard therapy existed.
2.
Hematopoietic malignancies.
3.
Untreated or symptomatic central nervous
2. HER3 expression expected.
3. Tumor(s) at least 1 lesion 1.5 cm or greater
system metastases.
4. >18 years
5. Eastern Cooperative Oncology Group (ECOG)
performance status <2
4.
Known HIV or hepatitis C viral infection.
5.
Unresolved toxicities above Grade 1
6. Adequate organ function.
(except for Grade 2 lymphopenia, alopecia,
7. Left ventricular ejection fraction >50%
or both) from prior anticancer therapy)
8. Willingness and ability to undergo imaging
studies
6.
9. Available archived tissue for HER3-expression
Any comorbid medical condition that may
increase the risk of toxicity.
analysis
10. Adequate contraception by women of
childbearing potential
7.
Pregnancy or planned pregnancy
8.
Prior exposure to or known sensitivity to
11. Written informed consent.
any component of patritumab or 64CuDOTA-patritumab.
9.
Prior treatment with HER3 antagonists.
10. Any concomitant antitumor treatment.
11. Participation in any concurrent
investigational procedure or study.
Phase 1 Study of 64Cu-DOTA-Patritumab
Page 2 (Version 10.0 9-2-15)
Supplemental Table 2. Organ residence times in hours for all 5 dosimetry cohort subjects.
Subject ID
Organ/Tissue
1
2
3
4
5
Blood
9.26
7.97
8.53
9.02
8.74
Lung
0.24
0.14
0.28
0.24
0.19
Liver
12.2
8.02
8.62
11.37
8.99
Spleen
0.26
0.13
0.19
0.15
0.13
Kidney
0.28
0.28
0.36
0.27
0.32
Red marrow
0.85
0.73
0.78
0.82
0.80
Heart Content
0.57
0.49
0.53
0.56
0.54
Remainder of the
body
7.84
8.53
7.57
7.64
7.37
Phase 1 Study of 64Cu-DOTA-Patritumab
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Supplemental Table 3. Organ radiation doses (mGy/MBq) from PET/CT data.
Subject ID
Organ
1
2
3
4
5
Mean
SD
Adrenals
0.040
0.032
0.033
0.038
0.033
0.035
0.004
Brain
0.012
0.013
0.011
0.011
0.011
0.012
0.001
Breasts
0.017
0.016
0.015
0.016
0.015
0.016
0.001
Gallbladder
0.062
0.046
0.047
0.058
0.048
0.052
0.007
LLI Wall
0.015
0.016
0.014
0.015
0.014
0.015
0.001
Small Intestines
0.021
0.020
0.019
0.020
0.019
0.020
0.001
Stomach
0.024
0.021
0.020
0.022
0.020
0.022
0.001
ULI Wall
0.025
0.022
0.021
0.024
0.021
0.023
0.002
Heart Wall
0.079
0.068
0.071
0.076
0.072
0.073
0.004
Kidneys
0.097
0.091
0.113
0.092
0.102
0.099
0.009
Liver
0.58
0.38
0.41
0.54
0.42
0.46
0.086
Lungs
0.035
0.023
0.035
0.034
0.028
0.031
0.005
Muscle
0.017
0.017
0.016
0.017
0.015
0.016
0.001
Ovaries
0.017
0.017
0.016
0.016
0.016
0.016
0.001
Pancreas
0.037
0.030
0.030
0.035
0.030
0.032
0.003
Red marrow
0.046
0.040
0.041
0.044
0.042
0.043
0.002
Osteogenic cells
0.045
0.043
0.041
0.043
0.041
0.043
0.001
Skin
0.013
0.013
0.012
0.013
0.012
0.013
0.001
Spleen
0.124
0.066
0.092
0.075
0.066
0.085
0.025
Testes
0.012
0.013
0.012
0.012
0.012
0.012
0.001
Thymus
0.019
0.018
0.017
0.018
0.017
0.018
0.001
Thyroid
0.014
0.014
0.013
0.013
0.013
0.013
0.001
Urinary bladder wall
0.015
0.015
0.014
0.014
0.014
0.014
0.001
Uterus
0.017
0.017
0.015
0.016
0.015
0.016
0.001
Total Body
0.034
0.028
0.028
0.032
0.028
0.030
0.003
Effective Dose
Equivalent
(mSv/MBq)
0.074
0.055
0.061
0.068
0.059
0.063
0.008
Effective Dose
(mSv/MBq)
0.051
0.039
0.041
0.048
0.041
0.044
0.005
Phase 1 Study of 64Cu-DOTA-Patritumab
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Supplemental Figure 1. Study schema for Dosimetry and Receptor Occupancy Cohorts.
Phase 1 Study of 64Cu-DOTA-Patritumab
Supplemental Figure 2. Patient flow diagram.
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Phase 1 Study of 64Cu-DOTA-Patritumab
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Supplemental Figure 3. Mean serum patritumab concentrations vs. time for Day 8 after
administration of a single dose of patritumab 9 mg/kg (n=3) or 18 mg/kg (n = 7).
Phase 1 Study of 64Cu-DOTA-Patritumab
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Supplemental Figure 4a-4e. Time activity curves for patients 1 to 5 in the dosimetry cohort.
a)
b)
c)
Phase 1 Study of 64Cu-DOTA-Patritumab
d)
e)
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Phase 1 Study of 64Cu-DOTA-Patritumab
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