Clinical trial NCT01774071
Conditions: Prostate Cancer
Keywords: 89Zr-DFO-MSTP2109A tracer pet scan 12-178
Sponsor: Memorial Sloan Kettering Cancer Center
Start date: 2013-01-01; Completion date: 2023-05-02
Enrollment: 19 participants; Allocation: NON_RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this study is to see if a new diagnostic research agent named 89Zr-DFO-MSTP2109A can show prostate cancer tumors on a PET scan; as well as see how long 89Zr-DFO-MSTP2109A lasts in the blood when given in small amounts. DFO-MSTP2109A is an antibody that works against STEAP1 - found on the surface of prostate cancer cells. Attached to the DFO-MSTP2109A is a radioactive material called 89ZR, which allows it to be imaged by a PET scanner. The results of this study may help researchers know whether 89Zr-DFO-MSTP2109A can be used as a diagnostic agent for finding prostate cancer that have STEAP1 on its surface with a PET scanner. The reason why identifying STEAP1 on prostate cancer cells is that new therapies are being developed to target STEAP1 prostate cancer cells.

Detailed description:

Arms: arm 1: The first group of participants will include 6 participants whom will receive 10mg of 89Zr-DFO-MSTP2109A. A second group of 6 participants may receive twice the amount of antibody to determine if this results in better pictures of your tumors. Once we determine whether 10 mg or the larger 20 mg dose of 89Zr-DFOMSTP2109A is best and well tolerated we will use that amount for future participants in Group 2. arm 2: Once we determine whether 10 mg or the larger 20 mg dose of 89Zr-DFOMSTP2109A is best and well tolerated we will use that amount for future participants in Group 2. Group 2 will include up to 15 participants whom may receive a dose of up to 20mg.
Interventions: intervention 1: 89Zr- DFO-MSTP2109A intervention 2: 89Zr DFO-MSTP2109A
Intervention descriptions: intervention 1: If you are enrolled onto Group 1:

Once you are given the diagnostic agent, the following procedures will be done:

PET scans at the approximate times:

* 1-4 hours after the injection
* 24 hours after the injection (the next day, Day 2)
* 48-120 hours after the injection (on either Day 3, 4, or 5)
* 144-168 hours after the injection (on either Day 6, 7, or 8) You will also have research bloods drawn on the following times and days,
* Day 1: before the injection, approximately 5 minutes after, 30 minutes after, 1 hour after and 2-4 hours after the injection.
* At each time of your scheduled PET scan. intervention 2: If you are enrolled onto Group 2:

Once you are given the study drug, the following procedures will be done:

You will have one PET scan done. The timing of the PET scan will be determined at the time of your enrollment (\~ 3-7 days after injection).

No research blood work will be drawn in Group 2

Protocol documents:
Prot_SAP_000.pdf: 
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MEMORIAL SLOAN-KETTERING CANCER CENTER 
IRB PROTOCOL 
 
 
 
IRB#:12-178 A(3) 
 
A Phase I/II Study of 89Zr-DFO-MSTP2109A in Patients with Prostate 
Cancer 
PROTOCOL FACE PAGE FOR 
MSKCC THERAPEUTIC/DIAGNOSTIC PROTOCOL 
 
Principal Investigator/Department: 
Steven Larson, MD 
Radiology 
Co-Principal 
Investigator(s)/Department: 
Michael J. Morris, MD 
Medicine 
Investigator(s)/Department: 
Daniel Danila, MD 
Howard I. Scher, MD 
Susan Slovin, MD, PhD 
Dana Rathkopf, MD 
David Solit, MD  
Stephen E. Fleming, MD 
Jorge A. Carrasquillo, MD 
Neeta Pandit-Taskar, MD 
Josef Fox, MD 
Jason Lewis, PhD 
Pat Zanzonico, PhD 
Mithat Gonen, PhD 
Sarah Cheal, PhD 
Shutian Ruan, PhD 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Radiology 
Radiology 
Radiology 
Radiology 
Radiology 
Medical Physics 
Epidemiology/Biostatistics 
Radiology 
Radiology 
Consenting 
Professional(s)/Department: 
Michael J. Morris, MD 
Howard I. Scher, MD 
Susan Slovin, MD, PhD 
Dana Rathkopf, MD 
Daniel Danila, MD 
David Solit, MD 
Neeta Pandit-Taskar, MD 
Josef Fox, MD 
Steven M. Larson, MD 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Radiology 
Radiology 
Radiology 
 
 
Please Note: A Consenting Professional must have completed the mandatory Human 
Subjects Education and Certification Program. 
 
 
Memorial Sloan-Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 


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Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ........................................................................ 4 
2.1 
OBJECTIVES AND SCIENTIFIC AIMS ................................................................................... 7 
2.2 
Primary Objectives ............................................................................................................ 7 
2.3 
Secondary Objectives ....................................................................................................... 7 
3.1 
BACKGROUND AND RATIONALE ....................................................................................... 7 
3.2 
The Problem Being Addressed: Limitations of Conventional Imaging Modalities for 
Prostate Cancer Metastases .......................................................................................................... 7 
3.3 
Positron Emission Tomography (PET)............................................................................ 8 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION ............................................................ 12 
4.1 
Design ................................................................................................................................ 12 
4.2 
Intervention ........................................................................................................................ 13 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS ............................................................................... 13 
Drug Accountability ................................................................................................................... 13 
Package Labeling and Formulation .......................................................................................... 14 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY ............................................................................. 14 
6.1 
Subject Inclusion Criteria ................................................................................................... 14 
o 
Imaging modalities ................................................................................................................ 15 
Bone scan: new osseous lesion and/or ........................................................................................ 15 
MRI or CT: An increase in measurable soft tissue disease or the appearance of new sites of 
disease. ........................................................................................................................................ 15 
Or ............................................................................................................................................ 15 
6.2 
Subject Exclusion Criteria .................................................................................................. 15 
7.0 
RECRUITMENT PLAN ......................................................................................................... 16 
8.0 
PRETREATMENT EVALUATION ........................................................................................ 16 
9.1 
TREATMENT/INTERVENTION PLAN ................................................................................... 17 
9.2 
Pharmacokinetics ............................................................................................................ 17 
9.3 
Imaging ............................................................................................................................. 18 
9.4 
Whole body probe measurements (Cohort 1) ................................................................ 19 
9.5 
Assessment for Toxicity ................................................................................................. 19 
10.0 
EVALUATION DURING TREATMENT/INTERVENTION .................................................... 20 
Laboratory Safety Assessments ............................................................................................... 20 
Performance Status .................................................................................................................. 21 
Vital Signs ................................................................................................................................. 21 
11.0 
TOXICITIES/SIDE EFFECTS .................................................................................................. 23 


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12.1 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ........................ 25 
12.2 Bone Scan ........................................................................................................................ 26 
12.3 CT and MRI ....................................................................................................................... 26 
13.0 
CRITERIA FOR REMOVAL FROM STUDY .......................................................................... 26 
14.1 
BIOSTATISTICS ................................................................................................................... 26 
14.2 Primary Objective ............................................................................................................ 26 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
28 
15.1 Research Participant Registration ..................................................................................... 28 
15.2 Randomization ...................................................................................................................... 28 
16.0 
DATA MANAGEMENT ISSUES ........................................................................................... 28 
16.1 Quality Assurance ............................................................................................................. 29 
16.2 Data and Safety Monitoring ................................................................................................. 29 
17.0 
PROTECTION OF HUMAN SUBJECTS ............................................................................ 301 
17.1 Privacy ............................................................................................................................. 301 
17.2 Serious Adverse Event (SAE) Reporting ........................................................................ 301 
17.2.1................................................................................................................................. 312 
18.0 
INFORMED CONSENT PROCEDURES .............................................................................. 323 
19.0 
REFERENCES ....................................................................................................................... 334 
20.0 
APPENDICES ........................................................................................................................ 356 
Karnofsky Performance Scale ............................................................................................... 36 


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1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
Summary 
 
Metastatic prostate cancer is predominantly bone-tropic, and bone metastases result in blood 
dyscrasias, cord compression, fracture, pain, neurologic compromise, and death. New therapies 
are desperately needed, and many novel targeted therapies, androgen receptor (AR)-targeted 
treatments, chemotherapies, vaccines, immunologic drugs and immunotoxins are currently being 
tested. Unfortunately, drug development and clinical care for these patients is significantly 
hampered by the lack of any standard means of accurately assessing the primary reservoir of 
distant disease, which is embedded in the marrow of the axial skeleton. 
 
Bone scintigraphy demonstrates reactive bone deposition only and not the cancer itself. Bone 
lesions shown on computerized tomography (CT) and plain radiographs generally only appear as 
sclerotic lesions that bear no relation to active tumor size, nor can these methods distinguish 
between the healing effects of successful therapy vs. the osteoblastic response of bone to a 
tumor that is continuing to progress on therapy. 
 
The lack of good imaging methods hampers decision making in terms of when to apply or modify 
conventional treatment methods as well as limiting new drug development.  Accurate imaging 
modalities are particularly needed in the age of targeted or biologic therapies, where effective 
therapies may be cytostatic and may not result in significant prostate-specific antigen (PSA) 
declines. In such cases, molecular imaging may be the only means by which early biologic activity 
of a new drug may be detectable in a Phase I or Phase II study. Furthermore when targeted 
therapies are to be used it is desirable to have an imaging test that identifies that the target is 
present in order to select patients and that may be also be used to determine if the target is being 
“hit” or downregulated. Many examples of this target selection and monitoring approach exist. 
Examples include bone scan for selection of radionuclide therapy with Sm-153 EDTMP or Sr-89 
chloride, I-123 MIBG to select patients for I-131 MIBG therapy or In-111/Ga-68 Somatostatin 
receptor scintigraphy to select patients for Y-90/Lu-177 Somatostatin receptor therapy. 
 
The Memorial Sloan-Kettering Cancer Center (MSKCC) Genitourinary (GU) Oncology Service  
has long collaborated with the Nuclear Medicine Service and the Department of Radiology to 
develop novel imaging modalities for prostate cancer. Using the MSKCC clinical states model 
(Scher and Heller 2000) as a template for radiologic investigations as well as clinical 
investigations, we have established a methodology for exploring positron emission tomography 
(PET) in prostate cancer that controls for clinical state, disease progression, scanning algorithm, 
method of interpretation, data collection, and data analysis. Using these techniques, we have 
demonstrated that fluorine-18-fluorodeoxyglucose (FDG) PET can be used to detect disease and 
demonstrate treatment effects and that fluorinated dihydrotestosterone (FDHT) PET can be used 
to detect disease and demonstrate pharmacodynamic effects of AR-targeted agents (Morris, 
Akhurst et al. 2002; Larson, Morris et al. 2004; Zanzonico, Finn et al. 2004; Morris, Akhurst et al. 
2005). Furthermore we have collaborated on imaging and therapy based antibody approaches 
targeting Prostate Specific Membrane Antigen (PSMA). These approaches have shown the 
feasibility of using an antibody to target prostate cancer (Bander, Trabulsi et al. 2003; Nanus, 
Milowsky et al. 2003; Milowsky, Nanus et al. 2004; Bander, Milowsky et al. 2005; Morris, Divgi et 
al. 2005; Morris, Pandit-Taskar et al. 2007; Pandit-Taskar, Morris et al. 2008). Currently in 
collaboration with the chemistry core we have been developing Zirconium-89 (89Zr) , a positron- 
emitting radionuclide, labeled to J591 has been approved by the IRB (protocol #11-126) and 8 
patients have been accrued thus far (up to 4-28-2012) without dose limiting toxicity. J591 is an 
antibody that recognizes the external domain of prostate-specific membrane antigen. Furthermore 


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we have prepared clinical grade 89Zr trastuzumab and a protocol is being written. Thus we have in 
place the technology to develop 89Zr labeling of antibodies of interest. 
 
Six-transmembrane epithelial antigen of the prostate-1 (STEAP1)  is a multi-transmembrane, 
cell-surface antigen of unknown function that is overexpressed in 8 5 % of human epithelial 
prostate cancers. Genentech has developed an antibody, MSTP2109A that binds to STEAP1. 
They have developed an antibody drug conjugate (ADC) DSTP3086S  that contains the 
humanized lgG1 anti-STEAP1 monoclonal antibody MSTP2109A and a potent anti-mitotic 
agent, monomethyl auristatin E (MMAE), linked through a protease-labile  linker, 
maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (MC-VC-PAB). This reagent is 
currently in a phase I therapeutic multicenter trial in which MSKCC is participating (PI Daniel 
Danila protocol, MSKCC 11-016). Therefore it is desirable to develop an imaging reagent that 
identifies the presence and intensity of the target by in vivo imaging. In addition, if the tracer 
appears to identify prostate cancer metastases effectively, then it may further be developed as an 
imaging biomarker for prostate cancer even independent of the specific STEAP1-targeted 
therapy. 
 
 
Schema 
 
Cohort 1A and 1B will each have the same clinical characteristics and inclusion criteria 
requirements.  Both sets of patients will undergo serial pharmacokinetics and serial imaging 
exams post 89Zr-DFO-MSTP2109A injection. 
 
Upon the completion of pharmacokinetics and serial imaging (post Cohort 1A), patients will 
proceed accordingly based upon tumor detection observed, and whether there is suggestion of 
antigen sink or rapid clearance that affects tumor imaging. The difference between the 2 cohorts 
will be that 1A will receive 10 mg total of DFO-MSTP2109A and if cohort 1B is necessary, 
because criteria described above of suboptimal imaging or pharmacokinetics, patients will receive 
20 mg total of DFO-MSTP2109A.   From  cohort 1A (10mg)  or 1B (20 mg), we will decide what 
antibody amount (10 or 20 mg) is best and the optimal time of image acquisition.  Cohort 2 will 
then consist of patients with the same characteristics and inclusion criteria as in cohort 1A and 1B, 
with the only difference being that they will receive the best dose determined from cohort 1A or  
1B (10 or 20mg). Furthermore, they will not undergo pharmacokinetics and rather than serial 
imaging, the patients will only have one scan at an optimal time post injection of antibody 
determined from serial imaging of Cohort 1A and 1B. 


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Patients to undergo 
pharmacokinetics and serial imaging 
Eligible patients with prostate 
cancer will be registered to study 
Cohort 1A: Up to 6 patients will be enrolled to 
receive a single 10 mg dose of the 89Zr DFO- 
MSTP2109A tracer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2: Up to 15 patients will be 
enrolled. Use 20mg of total antibody as 
imaging dose for all patients. Single 
imaging and no pharmacokinetics 
*In the event that suboptimal 
imaging or pharmacokinetics 
occurs, patients will be placed 
into this ‘Cohort 2’ – 20mg of 
total antibody, opposed to 
10mg – optimal 
imaging/pharmacokinetics * 
• If tumor detection in <75% of STEAP1 
positive patients or 
• If there is suggestion of antigen sink or 
rapid clearance that affects tumor imaging 
Cohort 1B: Additional 6 patients will be 
enrolled to receive 20mg of 89Zr DFO- 
MSTP2109A tracer (pharmacokinetics and 
serial imaging) 
Cohort 2: Up to 15 patients will be 
enrolled. Use starting dose of 10mg of 
total antibody as imaging dose for all 
patients. Single imaging and no 
pharmacokinetics 
• If tumor targeting is observed in >75% of 
antigen positive patients 
• If no unexpected normal organ 
accumulation is observed that affects 
tumor imaging. 
• If there is no evidence of rapid clearance 
based on pharmacokinetic parameters 
that affects tumor imaging 


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2.0 
OBJECTIVES AND SCIENTIFIC AIMS 
 
2.1 
Primary Objectives 
 
• 
To determine feasibility, safety and tolerability of single dose administration of 
89Zr-DFO-MSTP2109A antibody. 
• 
To determine the ability of 89Zr-DFO-MSTP2109A PET to detect sites of 
metastatic prostate cancer. 
• 
To determine the pharmacokinetics (PK) and biodistribution of 89Zr-DFO- 
MSTP2109A. 
 
2.2 
Secondary Objectives 
 
• 
To determine the better/”adequate” 89Zr-DFO-MSTP2109A mass amount for 
tumor imaging (10 or 20 mg)  . 
• 
To determine optimal time relative to 89Zr-DFO-MSTP2109A administration for 
tumor imaging. 
• 
To use quantitative biodistribution data of 89Zr-DFO-MSTP2109A uptake to 
perform dosimetry estimates. 
• 
To correlate 89Zr-DFO-MSTP2109A uptake in tumors with STEAP1 antigen 
expression by  IHC 
• 
To explore whether 89Zr-DFO-MSTP2109A PET imaging results are related to 
patient outcome in patients being treated with DSTP3086S. 
 
 
3.0 
BACKGROUND AND RATIONALE 
 
3.1 
The Problem Being Addressed: Limitations of Conventional Imaging 
Modalities for Prostate Cancer Metastases 
 
Progressive prostate cancer spreads to bone more commonly than to any other site, yet 
monitoring bone metastases to quantify cancer regression and progression remains 
inconsistent at best. In addition, a significant percentage of patients have soft tissue, 
predominant nodal disease. The standard Phase II response criteria for solid tumors do 
not apply, and despite the rapid evolution of imaging modalities for prostate cancer, 
visualizing of tumor spread to bone is still in the early stages of development. For 
example, as seen on plain radiographs, when prostate cancer spreads to bone, tumor 
growth in the marrow results in osteoblastic changes, which, in the end stage, result in the 
complete replacement of the marrow space. While most physicians accept that sclerotic 
healing of a lytic lesion constitutes tumor regression, sequential monitoring of lesions that 
are initially sclerotic is problematic because the bone architecture rarely reverts 
histologically back to normal. Even if all tumor cells are destroyed, there may be no visible 
changes on standard scans. In these cases, only a direct biopsy can determine if viable 
tumor cells are present. Other imaging modalities have significant limitations in identifying 
viable tumor as described below.  Immunotherapy, radioimmunotherapy or antibody drug 
conjugate (ADC) related therapy are dependent on targeted antigen concentration. While 
patients may be selected based on antigen expression based on tumor biopsy, this is an 
invasive technique and is limited by impracticality of multiple tumor biopsy. In contrast, 
using a radiolabeled antibody approach allows one to non invasively select patients based 
on antigen content and allows assessment of multiple tumor sites. 


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Imaging modalities in prostate cancer 
 
3.1.1 Radionuclide bone scanning 
 
In prostate cancer, bone scintigraphy, although useful for staging, has limited 
usefulness because rather than providing a direct measure of cancer activity, it reflects 
the reaction of bone to the surrounding cancer. In addition, the common occurrence of 
the flare phenomenon (a paradoxical increase in intensity after successful therapy) 
complicates the interpretation of scans on a serial basis. 
 
 
3.1.2 Cross-sectional imaging 
 
The cross-sectional imaging modalities that are used to evaluate prostate cancer 
include CT, magnetic resonance imaging (MRI), and the emerging technology of 
magnetic resonance spectroscopy (MRS). The utility of each of these modalities varies 
according to the stage of disease. At present, no modality can distinguish viable 
disease from necrotic or nonmalignant tissue. 
 
CT is well suited for detecting soft tissue disease, but has limited utility in assessing 
early changes in bone. CT is not sensitive enough to detect small volume nodal 
disease or tumor in non enlarged lymph nodes. CT also does not effectively evaluate 
disease that is confined to the prostate and adjacent area. 
 
MRI: To provide the most accurate assessment in the region of the prostate, 
neurovascular bundles, and seminal vesicles, MRI is considered the modality of 
choice. In addition, MRI can detect soft tissue disease and is most useful to 
corroborate bone scintigraphy findings (particularly when the earliest involvement is 
thought to be present in the bone marrow). MRI is most sensitive in the axial skeleton 
and pelvis, and is less effective in the ribs, chest wall, and skull. 
 
 
3.2 
Positron Emission Tomography (PET) 
 
PET has advantages over conventional imaging methods because it quantitatively 
assesses biologic processes in vivo and can assess different processes using specific 
radiotracers. Processes that can be analyzed with currently available reagents include 
glucose and amino acid metabolism and proliferation, blood flow, and receptor status (i.e., 
androgen receptor). Most studies have focused on the accumulation of FDG. 
 
 
3.2.1 PET scanning with fluorine-18-fluorodeoxyglucose (FDG) 
 
During the past decade, investigators at MSKCC have shown that PET imaging in 
prostate cancer can be tested prospectively using rigorous, carefully controlled 
standard clinical trial designs traditionally reserved for therapeutics (Morris, Akhurst et 
al. 2002; Morris, Akhurst et al. 2005). The method has been to enroll patients 
registered in therapeutic clinical trials to the imaging trials to undergo imaging in 
conjunction with their treatment. 


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3.2.1.1 
FDG PET and bone metastases 
 
Previous studies found that the sensitivity of FDG PET for detecting metastases 
was poor. However, these were not prospective, and the populations studied were 
not controlled for progression, clinical state, or type of treatment (Apolo, Pandit- 
Taskar et al. 2008). These trials demonstrated the need for rigorous controls in 
prostate cancer clinical trials of new tracers. To that end, we examined a uniform 
cohort of patients with progressive metastatic prostate cancer. We tracked each 
bone lesion from inception to progression, starting with 1 scan before baseline and 
2 follow-up scans after baseline, if feasible. FDG PET was sensitive enough to 
identify active disease and distinguish it from quiescent or noncancerous lesions 
(Morris, Akhurst et al. 2002). 
 
3.2.1.2 
FDG PET and evaluation of treatment effect 
 
In our prospective study, FDG PET captured, in a single imaging modality, the 
information usually captured by the standard composite clinical endpoint of PSA, 
bone scintigraphy, and soft tissue imaging. Twenty-two patients with castrate 
metastatic prostate cancer registered to clinical trials of anti-microtubule 
chemotherapy also participated in our imaging study. We followed them to either 
progression or death. After 4 weeks of chemotherapy, FDG PET and PSA were in 
agreement in 86% of cases; in 91% of cases, FDG PET correctly identified 
whether the patient’s disease was progressing. After 12 weeks of therapy, FDG 
PET, PSA, and standard imaging were compared. PET correctly identified the 
clinical status in 94% of cases. These data suggest that FDG PET, when studied 
prospectively in a population rigorously controlled for clinical state and disease 
progression, can effectively demonstrate treatment effects (Morris, Akhurst et al. 
2005). FDG PET can demonstrate marked posttreatment changes in response to 
chemotherapy similar to PSA, furnishes information regarding tumor metabolism, 
and demonstrates antitumor effects on a lesional basis. By contrast, simultaneous 
bone scintigraphy demonstrates no such effects and is nearly useless in 
demonstrating post-treatment changes. 
 
 
3.2.2 
STEAP1 antigen and MSTP2109A antibody 
 
Six-transmembrane epithelial antigen of the prostate-1 (STEAP1)  is a multi- 
transmembrane, cell-surface antigen of unknown function that is overexpressed 
in  85% of human epithelial prostate cancers, and low and restricted expression 
only in normal prostate tissue (Hubert, Vivanco et al. 1999; Challita-Eid, Morrison 
et al. 2007). 
 
Genentech has developed a humanized anti-STEAP1 monoclonal lgG1 
antibody MSTP2109A that recognizes this antigen. An anti-mitotic agent 
monomethyl auristatin E (MMAE) based ADC DSTP3086S has been developed 
by Genentech, and is currently under clinical evaluation in a multicenter clinical 
trial in which MSKCC is participating. The ADC as a therapy takes advantage of 
the targeting capability of the antibody and the cytotoxic activity of MMAE, 
which binds to microtubules and disrupts the microtubule network. Following 
antigen-specific binding of the ADC, the complex of the target antigen and the 
conjugate is internalized and MMAE or MMAE-containing catabolites are 


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released intracellularly,  resulting in inhibition of cell division and growth, and 
culminating in cell death (Doronina, Toki et al. 2003; Francisco, Cerveny et al. 
2003). It is anticipated that presence of the antigen is a prerequisite for tumor 
targeting and delivery of the toxic pay load.  We believe that it would be useful to 
evaluate a radiolabeled anti-STEAP1 antibody to determine the presence and 
intensity of target antigen on prostate tumors, in vivo. 
 
Both the anti-STEAP1 antibody, MSTP2109A, and its ADC showed similar and 
high binding activity (low nanomolar) to human and cynomolgus monkey STEAP1 
but no binding to rat or mouse STEAP1 orthologues. The pharmacokinetics and 
disposition  of unconjugated antibody and its ADC are driven mainly by the 
anti-STEAP1 antibody component and expected to be similar between 
antibody and ADC. 
 
The pharmacokinetics of anti-STEAP1 antibody, MSTP2109A and its conjugate 
DSTP3086A were linear in both rats and non-tumor bearing mice, as expected for 
non-binding species. DSTP3086A also demonstrated linearity in cynomolgus 
monkeys  (a binding species) over the tested dose range i.e., 0.3-5.0 mg/kg), 
which is expected given the non-detectable level of STEAP1 expression  in normal 
tissues. 
 
MSTP2109A has been used in humans as the targeting moiety of an antibody drug 
conjugate (ADC DSPT3086S) that is being used in a Phase 1 trial at MSKCC..  The 
Anti-STEAP1 intact antibody MSTP2109A  has not been used in humans. Safety 
data in non-human primates and rodent are available for both the antibody 
MSTP2109A and the antibody drug conjugate DSPT3086S.  Anti-STEAP1 antibody 
MSTP2109A was included in non-GLP toxicity studies in both Sprague-Dawley rats 
and in cynomolgus monkeys. Single doses of 60 mg/kg MSTP2109A in rats and 2 
doses every 3 weeks of 24 mg/kg MSTP2109A exhibited no toxicologically 
significant changes compared to vehicle control. 
 
The primary safety signal identified for the anti-STEAP1 ADC DSTP3086S in 
cynomolgus monkeys and rats was bone marrow toxicity, specifically dose- 
dependent, reversible neutropenia. The toxicity findings with the ADC were 
consistent with the mechanism  of action (microtubule inhibition) of the cytotoxic 
component (MMAE) of DSTP3086S, and were considered to be MMAE specific 
and independent of STEAP1 target. 
 
A toxicity study in mice using our DFO-MSTP2109A formulation at 50 mg/kg did not 
show toxicity ( no observable effect level). 
 
The drug conjugate DSTP3086S has been used in 26 patients as of 08/22/2012 as 
part of an ongoing Phase I multi-center clinical trial - MSKCC protocol 11-016. 
Currently, enrollment is occurring at 2.8 mg/kg. Only two DLT have been observed 
consisting of transaminitis at the 2.25 mg/kg, and elevated liver enzymes in a 
patient treated at a dose level of 2.8 mg/kg. Reversible liver toxicity was observed 
in pre-clinical assessments with DSTP3086A and likely represents toxicity 
attributable to the drug conjugate Otherwise, treatments have been very well 
tolerated with very mild side effects possibly related to treatment such as Gr1 
hypotension constipation or diarrhea. Other 89Zr-labeled antibodies have been used 
in patients with good tumor localization and tolerated well (Borjesson, Jauw et al. 
2006; Borjesson, Jauw et al. 2009; Dijkers, Munnink et al. 2010). As of date, the 
protocol continues to accrue. 


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3.2.2.1 
89Zirconium 
89Zr is an attractive metallo-radionuclide for use in immuno-PET due to favorable 
decay characteristics. It has a 78.4h half life and a 22.7% positron yield. 
 
Standardized methods for the routine production and isolation of high-purity and 
high-specific-activity 89Zr using a small cyclotron are reported. Optimized cyclotron 
conditions reveal high average yields of 1.52 ± 0.11 mCi/muA*h at a proton beam 
energy of 15 MeV and current of 15 muA using a solid, commercially available 89Y- 
foil target (0.1 mm, 100% natural abundance). 89Zr was isolated in high 
radionuclidic and radiochemical purity (>99.99%) as (89Zr)Zr-oxalate by using a 
solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The 
effective specific activity of 89Zr was found to be in the range of 5.28−13.43 
mCi/microg (470−1195 Ci/mmol) of zirconium. 
 
New methods for the facile production of (89Zr) Zr-chloride are reported. 
Radiolabeling studies using the trihydroxamate ligand desferrioxamine B (DFO) 
gave 100% radiochemical yields in <15 min at room temperature, and in vitro 
stability measurements confirmed that (89Zr) Zr-DFO is stable with respect to ligand 
dissociation in human serum for >7 days. Small-animal PET imaging studies have 
demonstrated that free 89Zr (IV) ions administered as (89Zr) Zr-chloride accumulate 
in the liver, whilst (89Zr) Zr-DFO is excreted rapidly via the kidneys within <20 min. 
 
These results have important implications for the analysis of immuno-PET imaging 
of 89Zr-labeled monoclonal antibodies. The detailed methods described can be 
easily translated to other radiochemistry facilities and will facilitate the use of 89Zr in 
both basic science and clinical investigations (Holland, Sheh et al. 2009; Holland, 
Caldas-Lopes et al. 2010; Holland, Divilov et al. 2010; Holland, Divilov et al. 2010). 
 
 
3.2.3 Pharmacokinetic and biodistribution of chimeric or humanized 
monoclonal antibodies. 
 
We have based our antibody mass dose selection on the lack of cross reactivity of the 
STEAP1 antigen in normal human tissues. Furthermore we have drawn on the 
experience with various other antibodies to select our initial mass of DFO- 
MSTP2109A. The pharmacokinetics of a variety of radiolabeled antibodies has been 
determined in humans. Some antibodies have cross reactivity with normal antigens in 
vivo and thus require a certain mass amount in order to optimize pharmacokinetics  
and biodistribution. As an example clinical trials with 89Zr trastuzumab have shown that 
mass of about 50 mg is necessary in trastuzumab naïve patients. In contrast, studies 
with the chimeric 89Zr-cmAb U36 found adequate targeting when using 10 mg of the 
IgG. We have utilized PET imaging of I-124 anti huA33 antibody to target A33 antigen, 
a transmembrane glycoprotein with homology to tight junction-associated proteins that 
is present in normal colon and small bowel epithelium as well as in over 95% of human 
colon adenocarcinoma and approximately 50% of gastric and  pancreatic cancers, 
while absent in most other human tissues and tumors (Sakamoto, Kojima et al. 2000). 
Our studies utilizing 10 mg of  I-124 A33 have shown excellent targeting and have 
demonstrated Vd close to that of plasma 3,257 + 631 mL, T1/2 of ~ 65 h and Co of 
~31.9%ID/L (Carrasquillo, Pandit-Taskar et al. 2011). In our experience the use of 10 
mg of I-124 chimeric antibody cG250 resulted in excellent imaging of renal cell tumors 


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(Divgi, Pandit-Taskar et al. 2007). The pharmacokinetic analysis in a clinical trial that 
used 2, 5, 10, 25 and 50 mg of I-131 cG250 showed that at the 2 mg dose levels there 
was faster clearance but at all other levels there was no dose response with a median 
T1/2 of 68.5 h. When doses of 25 and 50 mg of cG250 were administered there was 
less tumor uptake than at the 10 mg dose (Steffens, Boerman et al. 1997). Humanized 
antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic 
adenocarcinomas. A clinical trial using In-111 hPAM4  showed good targeting and 
similar pharmacokinetics of doses ranging from < 10 mg compared to 100 mg (Gulec, 
Cohen et al. 2011) with T1/2 of 91.2h. An ongoing clinical trial using I-124 GC33 
humanized antibody in patients with hepatocellular carcinoma, being performed at 
MSKCC by Ghassan Abou-Alfa and Jorge A. Carrasquillo has shown good targeting at 
doses of 10 mg (unpublished observation). In contrast, at considerably higher doses of 
GC33 (390 mg) tumor uptake was significantly blocked, down to 1/3 of that seen with 
the 10 mg dose (SUV 21versus 7). Therefore it is expected that antibodies that have 
little cross reactivity with normal tissue will exhibit favorable pharmacokinetic for tumor 
imaging with mass amount of approximately 10 mg. 
 
 
3.2.4 Rationale for 89Zr-DFO-MSTP2109A PET use in prostate cancer 
 
Various radionuclides are available to label monoclonal antibody for imaging, 
pharmacokinetics and biodistribution. Antibodies labeled with positron emitters have 
significant advantage compared to single photon emitters. These include the higher 
sensitivity, spatial resolution of PET and its quantitative ability. At MSKCC we have 
used various positron emitters for labeling antibodies. I-124 has been used by our 
group and is a good isotope for labeling non internalizing antibodies. Other groups 
have pioneered the use of 89Zr  labeled antibodies and its successful use in patients 
has been reported (Borjesson, Jauw et al. 2006; Dijkers, Munnink et al. 2010). It is well 
known that for antibodies that internalize there is significant improved retention of radio 
metals compared to Iodinated antibodies (Naruki, Carrasquillo et al. 1990). 89Zr has an 
ideal half-life that is well matched to the half life of intact IgG. Correlating STEAP1 
tumor targeting with the response to DSTP3086S may allow for optimal patient 
selection. Furthermore from this study we will determine the ability of 89Zr-DFO- 
MSTP2109A to identify metastatic castrate resistant prostate cancer. This may allow us 
to perform future studies to phenotype the cancer (FDG, PSMA, STEAP1 and 
androgen receptor status) and may have a potential role in other drug development. 
 
 
4.1 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.2 
Design 
 
Patients with progressive castrate resistant metastatic prostate cancer are eligible to 
register for this study, providing all other eligibility criteria are met. Patients can be co- 
registered to therapeutic clinical trials, but may not receive any therapeutic treatments 
associated with those trials within 4 weeks prior to our imaging study. 
 
We have based our selection of a 10 mg starting dose on the lack of cross reactivity of the 
STEAP1 antigen in normal human tissues and work with other antibodies reported in the 
literature.  Cross-reactivity of MSTP2109A antibody with normal and binding affinity was 
similar between cynomolgus monkey and human, the cynomolgus monkey serves as a 
pharmacologically relevant model to predict human pharmacokinetics. DSTP3086A 
demonstrated pharmacokinetic linearity in cynomolgus monkey over the tested dose 
range of 0.3-5.0 mg/kg. Therefore it is expected that there will be no antibody sink to 


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rapidly clear the antibody injected. An amount of 10 mg is expected to be adequate for 
tumor imaging. The rationale for 10 mg is based on the fact that this is an amount that  
has been used successfully with other antibodies that have minimal or minor cross 
reactivity with normal tissues in vivo (Divgi, Pandit-Taskar et al. 2007; Carrasquillo, Pandit- 
Taskar et al. 2011). Nonetheless, since no pharmacokinetic or imaging studies have been 
performed with 89Zr-DFO-MSTP2109A, initial studies must determine an acceptable mass 
for imaging. In order to streamline antibody mass selection, initial Cohort 1A patients (up  
to 6 in cohort) will receive 10 mg of 89Zr  -DFO-MSTP2109A and will undergo 
pharmacokinetics and serial imaging. Decision of whether to study a second cohort,  
Cohort 1B,  at a higher dose (20 mg) will be based predominantly on the basis of whether 
adequate tumor targeting is observed (tumor detection in >75% of STEAP1 positive 
patients). As secondary measure we will evaluate for unexpected normal organ 
accumulation, based on PET imaging and evidence of rapid plasma clearance based on 
pharmacokinetic parameters and tumor targeting. If adequate tumor targeting is achieved 
we will use the starting dose of 10 mg in patients enrolled in Cohort 2. The absence of 
antigen sink may be confirmed if pharmacokinetics show Vd of less than 3 times plasma 
volume, T1/2 is greater than 50 h and if visually there is no binding to normal tissues above 
that expected from blood pool.  If there is suggestion of antigen sink, and           
inadequate tumor targeting, we will evaluate an additional 6 patients who will receive total 
dose of 20 mg (Cohort 1B). The patients in Cohort 1B also will undergo pharmacokinetics, 
imaging and whole body measurements as outlined for the 10 mg cohort in section 9.0. 
Once the milligram dose to be administered is selected, a second group of patients 
(Cohort 2) consisting of up to 15 patients will be enrolled, that will have only 1 whole-body 
scan, at a time point to be determined based on the results of Cohort 1A or 1B patients. 
 
Because 89Zr-DFO-MSTP2109A has not been evaluated in patients, toxicity assessment 
will be performed using Common Terminology Criteria for Adverse Events (CTCAE) v4. 
 
 
4.3 
Intervention 
 
The intervention is the administration of a single dose of the 89Zr-DFO-MSTP2109A tracer 
for imaging purposes. In Cohort 1A or 1B, after administration of the experimental tracer, 
the patient will undergo up to four PET scans during the 7 days post injection, whole body 
probe measurements and pharmacokinetics. In Cohort 2, patients will undergo injection of 
89Zr-DFO-MSTP2109A, and they will undergo one PET scan from top of skull to mid thigh 
(this may be adjusted based on known extent of disease) and no pharmacokinetics will be 
performed. The primary population will be those who are planning to enroll in the 
therapeutic trial using DSTP3086S (11-016), although for Cohort 1A, 1B and potentially 
Cohort 2 patients that meet the inclusion criteria may be enrolled even if not considered 
for DSTP3086S therapy. No clinical management decisions will be made based on 89Zr 
DFO- MSTP2109A imaging. Patients may not be re-imaged on this trial. 
 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 
 
MSTP2109A is a humanized antibody that targets STEAP1 that will be labeled with 89Zr. We will 
use 89Zr, a positron-emitting radionuclide, labeled to MSTP2109A via DFO. This protocol will 
explore the feasibility of 89Zr-DFO-MSTP2109A PET imaging; the tracer’s pharmacokinetic (PK) 
and biodistribution properties; its ability to detect disease relative to standard imaging modalities. 
 
 
Drug Accountability 


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The investigator is obliged to keep sufficient documentation of the delivery and use of the 
investigational product. The documentation will include administration date/ time, calibration 
date/time, quantity, patient code, lot number and date of destruction. The investigator should 
maintain records that document adequately that the patients were provided the dose specified in 
the protocol and reconcile the medication received for the study. The label of each vial will contain 
the patient code and lot number, patient and radiopharmaceutical information will be entered in  
the radiopharmacy drug accountability forms. The investigator may assign some or all of the 
investigator’s duties for drug accountability to an appropriate individual such as pharmacist or 
nuclear medicine technician who is under the supervision of the investigator. 
 
89Zr-DFO-MSTP2109A 
Radiolabeling of 89Zr-DFO-MSTP2109A: The DFO-MSTP2109A will be labeled in accordance 
with the MSKCC investigator sponsored IND. The study will be performed under an FDA 
approved IND for 89Zr-DFO-MSTP2109A, no studies will be performed until the IND is approved. 
The final product will contain up to 5 mCi and will have been brought up to desired total antibody 
quantity (e.g. 10 or 20 mg) of DFO-MSTP2109A by adding cold carrier dfo-MSTP2109A as 
outlined in the design section.  The product will have met the release criteria specified in the IND. 
Immunoreactivity  and sterility assays will be performed post release. 
 
The investigational product label will include the patient name, MRN and the calibration date and 
time. The investigational product is to be used within 8 hours of manufacturing. 
 
Package Labeling and Formulation 
 
Each   vial   will   contain   the  following   information   on  the   label:   89Zr-DFO- 
MSTP2109A 
1 vial (10 mL) contains: up to 5 mCi / ~10 ML 
Calibration date: <insert time>(EST)_on <insert date>_ 
Must use within 8 hours of manufacturing! 
Excipients: Human serum albumin; sodium phosphate 
Lot : <insert lot number> 
Patient Name: <insert patient code> 
Clinical study MSKCC IRB #:<insert IRB#> 
PI: <insert PI name > 
Caution: New Drug Limited to Investigational Use by Qualified Investigator Only 
STORE AT 2°C-8°C IN A REFRIGERATOR or up to 4h at room temperature. 
DO NOT USE IF CLOUDY OR CONTAINS PARTICULATE MATTER 
Manufactured by: Radiohemistry Core MSKCC 
 
Images will be corrected for attenuation and scatter and adjusted for system sensitivity 
and providing parametric images in terms of standardized uptake values (SUV) (= μCi 
found/gm tissue / (μCi injected/gm body mass). 
 
 
6.1 
CRITERIA FOR SUBJECT ELIGIBILITY 
 
6.2 
Subject Inclusion Criteria 
 
To be included in this study, patients should be eligible for enrollment into protocol 11-016 
(therapy with the DSTP3086S ADC) or meet all of the following criteria: 
 
• 
Patients meeting the criteria for enrollment on research protocol 11-016 to receive 


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DSTP3086S ADC (therapeutic ADC based on MSTP2109A) will be the preferred 
patients for this study. Patients that are to  receive  DSTP3086S will not be 
injected with  DSTP2086S until  imaging with  89Zr-DFO-MSTP2109A is finished, 
approximately 1 week. 
• 
Adult male >21years of age 
• 
Visible lesions by either CT, bone scan or MRI consistent with metastatic disease 
o Metastatic  progressive disease 
 
o Imaging modalities: 
Bone scan: new osseous lesion and/or 
MRI or CT: An increase in measurable soft tissue disease or the 
appearance of new sites of disease. 
 
Or 
 
PSA Changes 
Minimum No. of 
determinations 
Interval 
Percentage 
increase over 
range of values 
Androgen 
independent 
3 
2 
> 1Week 
> 2Week 
25% 
 
• 
Patients with histologically confirmed prostate cancer at MSKCC 
 
• 
STEAP1 antigen positive tissue known from prior IHC testing or  if STEAP1 status 
is not known archival sample will be sent to Genentech for IHC. Samples need to 
be positive, when feasible metastatic lesions will be tested preferentially rather 
than the primary. 
 
• 
Performance status of 60 or higher (Karnofsky scale) (Appendix A) 
 
• 
Ability to understand and willingness to sign a written informed consent document 
 
• 
PSA levels to be taken within 2 weeks of antibody administration. 
 
 
6.3 
Subject Exclusion Criteria 
 
Patients meeting any of the following exclusion criteria will not be eligible for study entry: 
• 
Previous anaphylactic reaction to human, humanized or chimeric antibody 
• 
Hematologic 
o Platelets <75K/mcL 
o ANC <1.0 K/mcL 
• 
Hepatic laboratory values 
o Bilirubin >1.5 x ULN (institutional upper limits of normal) 
o AST/ALT >2.5 x ULN 
• 
Renal laboratory values 
o eGFR < 30mL/min/1.73m2 
• 
Patients with history of hypersensitivity reaction to any component of 89Zr-DFO- 
MSTP2109A, including DFO. 


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7.0 
RECRUITMENT PLAN 
 
Recruitment Plan (with Limited Waiver of Authorization) 
A member of the 11-016 clinical trial or the patient’s treatment team at MSKCC will identify 
potential study participants.  Men of all races and ethnic groups will be considered for study 
participation.  Candidates must conform to all inclusion and exclusion criteria to be accepted into 
the study. 
If the investigator is a member of the treatment team, s/he will screen their patients’ medical 
records for suitable research study participants and discuss the study and their potential for 
enrolling in the research study.  Potential subjects contacted by their treating physician will be 
referred to the investigator/ research staff of the study. 
The principal investigator may also screen the medical records of patients with whom they do not 
have a treatment relationship for the limited purpose of identifying patients who would be eligible 
to enroll in the study and to record appropriate contact information in order to approach these 
patients regarding the possibility of enrolling in the study. 
During the initial conversation between the investigator/ research staff and the patient, the patient 
may be asked to provide certain health information that is necessary to the recruitment and 
enrollment process. The investigator/ research staff may also review portions of their medical 
records at MSKCC in order to further assess eligibility.  They will use the information provided by 
the patient and/or medical record to confirm that the patient is eligible and to contact the patient 
regarding study enrollment. If the patient turns out to be ineligible for the research study, the 
research staff will destroy all information collected on the patient during the initial conversation 
and medical records review, except for any information that must be maintained for screening log 
purposes. 
In most cases, the initial contact with the prospective subject will be conducted by either the 
treatment team, investigator or the research staff working in consultation with the treatment team. 
The recruitment process outlined presents no more than minimal risk to the privacy of the patients 
who are screened and minimal protected health information (PHI) will be maintained as part of a 
screening log.  For these reasons, we seek a (partial) limited waiver of authorization for the 
purposes of (1) reviewing medical records to identify potential research subjects and obtain 
information relevant to the enrollment process; (2) conversing with patients regarding possible 
enrollment; (3) handling of PHI contained within those records and provided by the potential 
subjects; and (4) maintaining information in a screening log of patients approached (if applicable). 
 
Estimated breakdown of target population 
 
% Native American/Alaskan 0% 
% Asian/Pacific Islander 
1% 
%Black Non Hispanic 
3% 
% Hispanic 
1% 
% White Non-Hispanic 
94% 
% Other 
1% 
 
8.1 
PRETREATMENT EVALUATION 
 
• 
History and physical examination 
• 
Laboratory studies (within 2 weeks before study entry): 
o Complete blood count 
o PSA 


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o Serum BUN, creatinine, AST, ALT, total bilirubin, alkaline phosphatase, 
and albumin 
o eGFR assessment 
• 
Standard clinically indicated imaging studies (within 4 weeks before study entry or up to 
2 weeks after entry, provided the patient has not received treatment). No intervening 
new therapy is allowed between conventional imaging studies and the 89Zr- 
DFO-MSTP2109A 
o Bone scintigraphy 
o CT of chest, abdomen, and pelvis with contrast, unless contraindicated on 
clinical grounds (allergy or renal insufficiency).  MRI is acceptable if CT is 
clinically contraindicated 
o Modified MRI of the pelvis, if clinically indicated 
 
• 
If STEAP1 status is not known from prior testing patient archival tissue  will be sent to 
Genentech to determine presence of STEAP1 antigen.. 
 
 
9.1 
TREATMENT/INTERVENTION PLAN 
 
9.2 
Pharmacokinetics 
 
Patients are not required to fast before 89Zr-DFO-MSTP2109A injection or imaging. 
 
Catheter insertion and Pharmacokinetics 
 
If feasible, 2 intravenous catheters (Hep-Lock) will be placed by staff in the Nuclear 
Medicine department for radiopharmaceutical administration and blood sampling, or 
alternatively a central line may be used for injection or sampling. The intravenous catheter 
will be removed at the conclusion of the imaging session.  If two lines are not feasible, one 
line will be used for both injection and PK sampling with intervening 10 cc saline flush and 
change of catheter hub. Patients in Cohort 2 (no pharmacokinetics, will not require a 
second catheter). 
 
89Zr-DFO-MSTP2109A: To determine clearance and for metabolite analysis of the drug, 
Cohort 1A and 1B patients (up to 6 patients per cohort) receiving 89Zr-DFO-MSTP2109A 
will have serial blood samples drawn.  Blood samples will be obtained in green top tube: 
• 
Just prior to injection of 89Zr-DFO-MSTP2109A (baseline) 
• 
Approximately 5 ± 2, 15 ± 5, 30 ± 9, 60 ± 19, and 120 to 240 minutes after 
injection of the tracer. 
• 
One sample at the time of each subsequent day of imaging (24 + 8h, ~48-96h 
and ~120-168h post injection). 
 
 
These data are used to determine the time-activity curves for plasma (% injected 
dose/liter).  Blood is centrifuged, and the plasma pipetted and counted.  Samples may be 
tested for breakdown products by TCA or HPLC. Blood will also be aliquoted for 
sampling, if in the first 3 patients no binding is observed to blood elements only plasma 
sampling will be counted in subsequent patients. 
 
For each blood sample, 4-6 mL of blood will be drawn in green top tubes. 
 
Patients in Cohort 2 will undergo injection and 1 imaging session, but no pharmacokinetics 
will be performed. 


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9.3 
Imaging 
 
89Zr-DFO-MSTP2109A 
Radiolabeling of 89Zr-DFO-MSTP2109A: The DFO-MSTP2109A will be labeled in 
accordance with the MSKCC investigator sponsored IND. The study will be performed 
under an FDA approved IND for 89Zr-DFO-MSTP2109A, no studies will be performed until 
the IND is approved.  The final product will contain up to 5 mCi and will have been brought 
up to desired total antibody quantity (e.g. 10 or 20 mg) of DFO-MSTP2109A by adding 
cold carrier dfo-MSTP2109A as outlined in the design section.  The product will have met 
the release criteria specified in the IND. Immunoreactivity  and sterility assays will be 
performed post release. 
 
The investigational product label will include the patient name, MRN and the calibration 
date and time. The investigational product is to be used within 8 hours of manufacturing. 
 
PET scanning: In order to provide reproducible clinical data, we will acquire all 89Zr-DFO- 
MSTP2109A PET scans on the GE PET-CT scanner DSTE at MSKCC or the same or a 
newer generation scanner. Once a study is begun in one scanner, it will be continued on 
the same scanner unless malfunction/emergency issues prevent this.  Intravenous 
injection of 89Zr-DFO-MSTP2109A (maximum of 5 mCi ± 10%) will be given over 5-15 
minutes.  Initially we will start with ~ 5 mCi of 89Zr-DFO-MSTP2109A; the activity may be 
adjusted downward based on visual review of image quality.  A PET-CT scan extending 
from top of skull to mid thighs will be performed to determine the biodistribution. The low 
dose CT portion of the 89Zr-DFO-MSTP2109A on the first day will utilize 80 mA (low mA) 
and on subsequent days, we will use 10 mA in order to minimize radiation exposure. In 
order to minimize imaging time, lower limbs will be included only for patients with known 
lesions in lower limbs on previous imaging and if at least 5 other lesions are not identified 
in the torso. 
 
Active lesions  will be identified (Nuclear Medicine investigator and MM) based on 
conventional images and those thought to represent active disease based on review of the 
patients conventional images and treatment history (ie external radiation) will be 
considered as lesions for determination of antibody localization. A lesion  will be 
considered present if there is greater localization than that expected based on blood pool 
distribution of the tracer.  Given that at present we do not know the heterogeneity of the 
antigen between lesions or between primary and metastatic disease a patient will be 
considered positive if any  of the active lesions are identified with the 89Zr-DFO- 
MSTP2109A . We will, nonetheless tabulate the number of lesions and their status based 
on 89Zr-DFO-MSTP2109A. When pathologic material that has been evaluated for the 
presence of STEAP1 is available for any specific lesion, we will correlate the presence of 
STEAP1 with imaging results. 
 
Patients in Cohort 1A (and if performed Cohort 1B) will also have imaging at 4 time points 
post-injection to allow for selection of optimal imaging time and dosimetry determination. 
For these patients, top of skull to mid thigh scans will be acquired: 
 
• 
Within one to four hours following injection of tracer on Day 1 
• 
~24 ± 8hours post-injection (Day 2) 
• 
~48−96 hours post-injection (once during Days 3−5) 
• 
~120−168 hours post injection (once during Days 6−8) 


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Images will be analyzed with ROI and SUVmean and max measurements will be obtained. 
The serial quantitative data obtained over the various organs of interest (heart, liver, 
spleen, kidney, lung and any other organ that exhibits uptake will be collected. These  
data can then be utilized to determine organ time activity curves and the dosimetry can be 
calculated. Uptake and clearance values will be summarized using descriptive statistics 
(mean, median standard deviation.  Once the biodistribution and pharmacokinetics have 
been characterized, subsequent patients will not require serial imaging and 
pharmacokinetics, but rather will have a single scan at an optimal time point determined 
based on the patients in cohort 1A and or cohort 1B. We will determine the time at which 
the greatest number of lesions are seen. This is likely to be between 3-8 days, but choice 
will be based on the first Cohort 1 patients’ data, using the most frequent day at which the 
most lesions are seen and/or at times at which best contrast is observed determined 
visually.  Thus, for the remainder of the patients in Cohort 2, PET scan will be performed 
once. The timing of this scan will be determined based on findings from Cohort 1A and/or 
1B, as described above. 
 
Infusion reactions with MSTP2109A intact IgG have not been evaluated. Infusion reaction 
to the ADC DSTP3086S antibody drug conjugate in 18 patient treated thus far have been 
minor and not clinically significant (i.e. none or Gr1).In the event of fever, rigors, shortness 
of breath, or other evidence of infusion reaction, patients may receive diphenhydramine 
25-50 mg IV and Tylenol 650 mg PO as felt to be clinically appropriate by the treating 
physician.  The emission data are typically acquired for 3−10 minutes per bed position 
depending upon the time post-injection and visual quality of the images. Index lesions will 
be identified based on the patient’s conventional diagnostic imaging. 
 
Images will be stored as Digital Imaging and Communications in Medicine (DICOM) on the 
PACS and HERMES.  Images to be sent out to Genentech will be burned on a CD or 
equivalent by patient.  All images will be anonymized according to institutional policy with 
the patients code used as identifiers. 
 
No decision on the patients’ health care management will be made on the basis of 
Imaging with 89Zr-DFO-MSTP2109A. 
 
9.4 
Whole body probe measurements (Cohort 1) 
 
Patients in Cohort 1 will undergo whole body dose measurement using a NaI probe placed 
at ~3 meters from the patient. These measurements will be performed the day of  
injection of 89Zr-DFO-MSTP2109A before voiding and after first void, and at each time the 
patient returns for imaging (typically less than 5 minutes). 
 
9.5 
Assessment for Toxicity 
 
Safety Outcome Measures (CTCAE v4) 
Infusion Reaction 
Patients will be monitored during and after 89Zr-DFO-MSTP2109A infusion for 90 
minutes after the infusion.  Patients who experience infusion-related symptoms should 
be managed as directed in Table 1. 
 
The safety and tolerability of 89Zr-DFO-MSTP2109A wi l l be assessed using the 
following primary safety outcome measure: 


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• 
Incidence, nature, and severity of adverse events up to 1 week following 
antibody administration. 
• 
Change in vital signs during administration 
 
 
Table 1 
Management of Infusion-Related Symptoms 
 
Infusion-Related 
Symptoms 
Guidance 
Grade 1 
• 
Slow or hold infusion 
• 
Give supportive treatment 
• 
Upon symptom resolution, may resume infusion rate escalation 
at the investigator’s discretion 
Grade 2 
• 
Slow or hold infusion 
• 
Give supportive treatment 
• 
Upon symptom resolution, may resume infusion-rate escalation 
at the investigator’s discretion 
Grade 3 or Grade 4 
• 
Discontinue infusion 
• 
Give supportive treatment 
Patient may be imaged if sufficient tracer has been administered and 
the patient is stable, at the discretion of the administering investigator. 
 
Given that this is a humanized antibody and the antibody will be administered only once 
under this protocol the likelyhood of development  of human anti human antibody is low. 
Patients enrolled,  who are being treated with the ADC under protocol 11-016 will be 
monitored for the presence of anti-ADC antibodies as is currently stated in that study. 
Thus the presence, if any,  of anti MSTP2109A, that would potentially interfere with ADC 
targeting will be evaluated in those patient on protocol 11-016.  Baseline serum and 4-6 
wk post infusion serum (serum separator or red top tube) will be collected and banked for 
future determination of HAHA response as requested by the FDA (Dr. Carrasquillo lab, 
storage approximately -70oC). 
 
10.0   EVALUATION DURING TREATMENT/INTERVENTION 
 
Laboratory Safety Assessments 
 
Blood testing: 
Hematology and blood chemistry assessments (CBC, PSA, serum BUN, creatinine, AST, ALT, 
total bilirubin, alkaline phosphatase, albumin, blood glucose levels, and serum testosterone level) 
will be done at the time points described in Table 2. Additional blood tests may also be performed 
at the discretion of the investigator for the purposes of planning treatment administration, dose 
modification, or investigation and follow-up of adverse events. These additional tests will not be 
documented in the CRF. 
Serum samples collected from baseline and 4-6 weeks after administration of DFO-MSTP2109A 
will be stored to assay for immune response to  89Zr-DFO-MSTP2109A (assay to be 
developed).This assay may be done in house or shipped to Genentech for processing. 
 
Physical examination: 
A physical examination including, but not limited to, general appearance, skin, neck, eyes, ears, 


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throat, lungs, heart, abdomen, lymph nodes, extremities, and nervous system will be performed. 
The physical examination will include examination of known and suspected sites of disease. 
Physical examination results, height and weight will be recorded at baseline . 
 
Performance Status 
 
Performance status will be assessed using the Karnofsky Performance Status scale (Appendix 
A). 
 
Vital Signs 
 
Blood pressure and heart rate will be obtained at the time points outlined in the flowchart. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 2 
Schedule of Assessments 
 
Cohort 1 (A and B): 
Screeninga 
Day 1 
Day 2 
Days 3-5 
Days 6-8 
4-6 wks 
post 
dose 
Within 4 
weeks 
Within 14 
days 
Informed consent 
X 
Demographics 
X 
Medical history 
X 
Concomitant medications 
X 
Physical exam 
X 
Performance status 
X 
Vital signsb 
X 
X 
X 
X 
X 
Laboratory studiesc 
X 
X 
Serum sample for banking 
X 
X 
Radiographic studiesd 
X 
IHC for STEAPe 
Prior to 
enrollment 
89Zr-DFO-MSTP2109A 
tracer administration 
X 


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a Screening evaluation should be performed following informed consent and within 4 weeks before study entry, 
except when noted otherwise. Evaluations performed as standard of care before informed consent but within 
the 4-week window need not be repeated. 
b 
Vital signs will be monitored prior to infusion and every 30 minutes for at least 2 h or later if the patient is still in 
the department for imaging. 
c 
Within 14 days laboratory studies include CBC, PSA, serum BUN, creatinine, AST, ALT, total bilirubin, alkaline 
phosphatase, albumin, blood glucose levels, and serum testosterone level. All laboratory studies are to be 
performed up to 2 weeks before study entry (serum testosterone level may be up to 4 weeks before study 
entry).   At Days 6 to 8  CBC and comprehensive labs will be obtained. 
d 
Radiographic evaluations include bone scintigraphy, CT of chest, abdomen and pelvis (MRI is acceptable if CT 
is clinically contraindicated), and modified MRI of the pelvis, if clinically indicated. All radiographic studies are to 
be performed within 4 weeks before, or up to 2 weeks after study entry, provided the patient has not received 
treatment. 
e 
sample sent out to Genentech 
f 
Following injection with the 89Zr-DFO-MSTP2109A  tracer, the patients enrolled in the study (Patients Cohort 1 
A and or 1B) will have serial whole-body PET-CT scans (WBS) performed to determine the biodistribution of 
the tracer. PET scans  will be acquired: 1−4 hours following injection of the tracer, ~24 h + 8 h post-injection, 
~48−96 hours post injection, and ~120−168 hours post injection. Slight variations in times due to scheduling or 
technical difficulties will not be considered violations 
g 
Whole body counts (WBC) using a probe will be performed during the imaging in the first 12 patients and the 
exact time recorded: 
o 
Within 0.1 to four hours following injection of tracer on Day 1 (prior to voiding) and post voiding 
o 
24 + 8 hours post-injection (Day 2) 
o 
~48−96 hours post-injection (once during Days 3−5) 
o 
~120−168 hours post injection (once during Days 6−8) 
h 
For the first 12 patients enrolled, serial blood samples will be obtained for biodistribution, metabolite analysis of 
the 89Zr-DFO-MSTP2109A  compound will be performed on selected samples. Samples will be obtained just 
prior to injection of the 89Zr-DFO-MSTP2109A  tracer, and at 5 ± 2 minutes, 15 ± 5, 30 ± 9, 60 ± 19 minutes, 
and 120 − 240 minutes after the injection of the tracer on 24+8, and at the time of each subsequent day of 
imaging , ~48-96, ~120-168, slight variations in times due to scheduling or technical difficulties will not be 
considered violations. 
 
 
 
Cohort 2: 
Screeninga 
Day 
1 
Day 
TBD 
Follow up 
Within 
4 weeks 
Within 
14 days 
~1 weeks post 
dose (Day6-8) 
4-6 weeks 
post dose 
Informed consent 
X 
Demographics 
X 
Medical history 
X 
Concomitant medications 
X 
Physical exam 
X 
Performance status 
X 
Vital signsb 
X 
X 
X 
Laboratory studiesc 
X 
X 
Serum sample for banking 
X 
X 
Radiographic studiesd 
X 
Adverse events on day of 
imaging 
X 
X 
X 
X 
Serial whole-body scans 
(Cohort 1A and 1B)f 
X 
X 
X 
X 
Serial whole-body probeg 
X 
X 
X 
X 
Serial blood 
samplesh(Cohort 1A and 
1B) 
X 
X 
X 
X 


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a Screening evaluation should be performed following informed consent and within 4 weeks before study entry, 
except when noted otherwise. Evaluations performed as standard of care before informed consent but within 
the 4-week window need not be repeated. 
b 
Vital signs will be monitored prior to infusion and every 30 minutes for at least 2 h or later if the patient is still in 
the department for imaging. 
c 
Laboratory studies include CBC, PSA, serum BUN, creatinine, AST, ALT, total bilirubin, alkaline phosphatase, 
albumin, blood glucose levels, and serum testosterone level. All laboratory studies are to be performed up to 2 
weeks before study entry (serum testosterone level may be up to 4 weeks before study entry). Second set of 
laboratory on TBD will consist of CBC and comprehensive.  At TBD CBC and comprehensive will be 
repeated. 
d 
Radiographic evaluations include bone scintigraphy, CT of chest, abdomen and pelvis (MRI is acceptable if CT 
is clinically contraindicated), and modified MRI of the pelvis, if clinically indicated. All radiographic studies are to 
be performed within 4 weeks before, or up to 2 weeks after study entry, provided the patient has not received 
treatment. 
e 
A phone call will be used to assess for changes in concomitant medications and any adverse events after all 
scans have been completed if the scanning time is less than 6-8 days. 
 
f 
For the 13th through 27th patients enrolled, only 1 PET scan will be performed, at a time point to be determined 
based on data from the first 12 patients. 
 
 
11.0 TOXICITIES/SIDE EFFECTS 
 
Risks 
 
89Zr-DFO-MSTP2109A PET/CT Scans 
As part of this scan there is radiation delivered from the 89Zr and from the low dose CT scan that 
are performed as part of the CT for attenuation correction and co-registration. Although any 
exposure to ionizing radiation has the potential to cause some harm to tissue, the radiation 
exposures in this study are comparable to the low-level exposures associated with common 
diagnostic procedures such as CT scanning. There remains a low theoretical risk of developing a 
cancer at some point later in life as a result of the radiation exposure received in this study. This 
risk is particularly low for adults given the fact that the radiation from the scans will be over 
several weeks. Participants should not father a baby while on this study. Acceptable birth control 
methods include abstinence, double barrier method, surgically sterilized patient or partner. This 
risk is much smaller that the clinical risks posed by the patient’s current cancer. 
 
DFO-MSTP2109A 
 
Potential risks associated with DFO-MSTP2109A are similar to those of other humanized 
antibody and include allergic reactions, characterized by fever, chills, and sometimes rashes or 
hives.  Less likely shortness of breath can occur. Rare allergic reactions can present as shock or 
death or swelling of the throat. Such reactions are usually addressed by stopping the 
administration of the drug, administering steroids, acetaminophen and/or diphenhydramine, and 
restarting the drug at a slower rate if the reaction is not severe. 
 
There is a very small risk of infection. This could cause itching or redness at the area on the 
patient’s arm where the IV was placed. 
89Zr-DFO-MSTP2109A tracer 
administration 
X 
Adverse events 
X 
X 
X 
Phone assessmente 
X 
Torso PET scanf(Cohort 2) 
X 


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Radiation Dosimetry 
 
Normal-organ radiation absorbed doses and the effective dose for 89Zr-DFO-MSTP2109A in 
human were estimated based on measured time-activity data in mice. The time-activity data 
(percent of the injected dose per gram (%ID/gm) versus time (t) post-administration) for each 
organ were fit to an exponential functions and the resulting function were analytically integrated 
(incorporating the radioactive decay of 89Zr) to yield the residence time (cumulated activity) of 89Zr 
in each organ. The mouse organ 89Zr residence times were converted to 89Zr residence times in 
human organs (for the 70-kg Standard Man anatomic model) by adjusting for the difference in 
fractional organ masses between mice and humans. The resulting human residence times were 
then entered into the OLINDA/EXM radionuclide dosimetry program, which implements the MIRD 
(Medical Internal Radionuclide Dosimetry) algorithm, to yield the normal-organ radiation absorbed 
doses (in rad) and effective dose (in rem) for 89Zr-DFO-MSTP2109A in man.  Assuming a 5-mCi 
administered activity of 89Zr-DFO-MSTP2109A and a low-dose (80 mA) and three very-low-dose 
(10-mA) CT scans are to be performed, with approximate CT effective doses of 0.90 rem and 
0.11 rem the radiation dosimetry is tabulated below. 
 
 
Table 3. 89Zr-DFO-MSTP2109A Absorbed Doses in 70-kg Standard Man per MIRD (OLINDA) 
Formalism Based on Biodistribution Data in Mice1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P2109A 
89Zr-DFO-MSTP2109A AP Antibody Radiation Doses in the 70-kg Standard 
Man 
89Zr Administered Activity: 
5 
mCi 
# of 80-mA CT scans: 
1 
Organ dose per 80-mA CT scan: 
0.90 
rem 
# of 10-mA CT scans: 
3 
Organ dose per 10-mA CT scan: 
0.10 
rem 
Total CT organ dose: 
1.20 
rem 
Absorbed Doses 
89Zr-DFO-MSTP2
rad/5 
rad/mCi 
mCi 
(rad) 
Adrenals 
1.56 
7.80 
9.00 
Brain 
0.68 
3.42 
4.62 
Gallbladder Wall 
1.32 
6.60 
7.80 
LLI Wall 
1.52 
7.60 
8.80 
Small Intestine 
1.25 
6.25 
7.45 
Stomach Wall 
1.39 
6.95 
8.15 
ULI Wall 
1.34 
6.70 
7.90 
Heart Wall 
1.50 
7.50 
8.70 
Kidneys 
2.33 
11.7 
12.9 
Liver 
1.81 
9.05 
10.25 
Lungs 
2.82 
14.10 
15.30 


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1mouse data obtained with 89Zr-DFO-MSTP2109A, conjugate generated at MSKCC. . 
 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 
 
Positive lesions on 89Zr-DFO-MSTP2109A will be defined visually as a focus of  accumulation of 
radioactivity that is deemed to not be physiologic and is higher than adjacent or contralateral 
background.  Antibody scan will be read blinded from clinical history and conventional imaging 
modalities. Two different experienced, blinded readers will visually analyze the 89Zr-DFO- 
MSTP2109A scans, and SUVmax/mean will be determined in lesions identified and in normal 
organs and blood pool. To study the accumulation and biodistribution of 89Zr-DFO-MSTP2109A in 
patients with progressive prostate cancer, the accumulation of 89Zr-DFO-MSTP2109A will be 
assessed for each site and compared with the baseline radionuclide bone scan, FDG PET/CT, 
CT, and/or MRI imaging. The definition of a positive lesion will be a lesion identified by an 
experienced reader on conventional imaging CT/MRI, bone scan, and/or FDG scan consistent 
with metastatic disease, as is currently done clinically.  Lesions on 89Zr-DFO-MSTP2109A or 
conventional imaging will be read in a scale of 1 to 5, 1= negative, 2 = probably negative, 3= not 
sure, 4= probably positive and 5= definitively positive. Once this is done, a consensus master list 
of lesions will be created that compares all imaging conventional imaging modalities(CT/MRI, 
FDG PET, bone scan), only those lesions that are conspicuously positive (i.e., “4 or 5”) by 
imaging will be considered as a positive site of disease. Discrepant findings between findings on 
conventional imaging and 89Zr-DFO-MSTP2109A modalities will be considered false positive or 
false negative.  Although it would be ideal to biopsy any site that is considered abnormal this is 
not logistically feasible or ethically acceptable. Successful imaging will be considered a sensitivity 
of detection of > 75% of patients that are STEAP1 positive.  One or 2 non-blinded readers 
(access to clinical, laboratory and imaging data) will identify “positive lesions” . 
 
As a first level, we will compare site by site. Since the individual modalities are based on different 
mechanisms of uptake, they may not have exact correspondence in space, since bone scan is a 
2D modality and looks at bone reaction and 89Zr looks at tumor antigen expression and is a 3D 
modality. 
 
For this purpose, we have made a list of standardized anatomic sites, to make sure that a positive 
Muscle 
1.21 
6.05 
7.25 
Pancreas 
1.42 
7.10 
8.30 
Red Marrow 
3.26 
16.3 
17.5 
Osteogenic Cells 
4.59 
23.0 
24.2 
Skin 
0.71 
3.55 
4.75 
Spleen 
1.98 
9.90 
11.10 
Testes 
0.82 
4.09 
5.29 
Thymus 
1.11 
5.55 
6.75 
Thyroid 
1.03 
5.15 
6.35 
Urinary Bladder Wall 
1.04 
5.20 
6.40 
Total Body 
1.31 
6.55 
7.75 
Effective Dose Equivalent 
1.87 
9.35 
10.55 
Effective Dose 
1.68 
8.40 
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lesion would have a positive 89Zr-DFO-MSTP2109A uptake. As a second level, we will compare 
lesion by lesion. Sensitivity and specificity of the imaging modalities will be compared in those 
patients receiving the better/”adequate” antibody mass. The “better/adequate” dose is defined as 
that which will allow us to visualize the targeted number of lesions defined and will consist of 
either 10 or 20 mg of DFO-MSTP2109A antibody. 
 
12.1 
Bone Scan 
 
Each lesion will be evaluated using the same 5-point scale. These findings will be 
compared with that of 89Zr-DFO-MSTP2109A PET scanning. 
 
Any discrepant reading of the antibody images or conventional  images will require review 
of the images by both readers who will discuss and reach a consensus, if a consensus 
cannot be reached the finding shall be considered “not sure” and categorized as negative. 
 
 
 
12.2 
CT and MRI 
 
Available CT and/or MRI imaging done clinically will be used as a correlative diagnostic 
imaging tool to compare to results of 89Zr-DFO-MSTP2109A PET scanning. Sensitivity of 
89Zr-DFO-MSTP2109A PET scanning to detect lesions will be compared with routine 
imaging including CT, MRI, FDG PET, and bone scans. Furthermore soft tissue lesions 
greater than 2 cm on CT or MRI will also be compared to 89Zr -DFO-MSTP2109A in order 
to overcome the issues of partial volume. 
 
13.0 
CRITERIA FOR REMOVAL FROM STUDY 
 
Participation in the study is strictly voluntary. Patients have the right to withdraw from the study at 
any time. If a patient chooses to withdraw, he or she must inform the investigator immediately. In 
addition, the investigator has the right to terminate participation of any patient at any time if it is 
deemed in the patient’s best interest. The reason and circumstances for premature 
discontinuation will be documented in the patient’s medical records. Possible examples for 
reasons of premature study withdrawal include withdrawal of consent, SAE or intolerable AE, or 
any other medical illness at investigator’s discretion. 
 
14.1 
BIOSTATISTICS 
 
14.2 
Primary Objective 
 
The primary objective of this protocol is to determine the feasibility, safety and tolerability 
of single dose administration of 89Zr-DFO-MSTP2109A antibody. 
A patient with STEAP1 positive tumor will be considered antibody-imaging-positive if 20% 
or more of the active lesions are detectable (STEAP1 positivity is an eligibility criterion for 
protocol 11-016 which forms the basis of eligibility for this protocol; see section 6 for 
details). Active lesion means any lesion that was identified by conventional imaging 
methods and clinical data at baseline. We have selected a low threshold of  20% for this 
first imaging study for 3 reasons: 1) we do not know what the heterogeneity of antigen 
expression is within a number of lesions in the same patient; 2) we will consider positive 
any lesion based on conventional clinical imaging criteria, in which case some lesions 
considered positive may be false positive and more importantly 3) our main emphasis is to 
evaluate whether patients whose tumor images are positive with 89Zr-DFO-MSTP2109A 
are more likely to have a response to the antibody based drug conjugate used under 


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protocol 11-016. Thus, we do not want to discard this agent if we can use it as a 
theranostic (defined as an agent that is integrated into the drug development process so 
as to guide patient selection and drug development) for the development of the antibody 
base drug conjugate being used under protocol 11-016. Nonethe less, we intend to 
evaluate  treatment response of all available lesions in this way we will maximize our 
ability to determine the relationship between uptake of antibody and response. 
 
If, for any patient, there is evidence of an “antigen sink” based on rapid clearance < 50 h or Vd>3 
times plasma volume, we will consider a patient antibody-imaging-positive if 20% or more of the 
active lesions are visualized. The presence of an “antigen sink” may bind a significant amount of 
antibody and make less available for binding to tumor. 
 
Antibody imaging will be considered feasible if 75% of the patients are antibody-imaging-positive 
as defined above..We will enroll 6 patients (cohort 1A) at the 10mg dose level for an initial decision 
on feasibility. If 4 or more of these patients have 20% or more of their active lesions detectable   
by 89Zr-DFO-MSTP2109A then we will consider the agent feasible for imaging,                 
otherwise we will proceed to cohort 1B. If the true feasibility rate is 40%, this rule will affords more 
than 82% chance that cohort 1B will be opened for enrollment; this probability is less than 17% if 
the true feasibility is 75%. We will also require that none of these patients experience dose severe 
toxicity attributable to the initial 10 mg  dose before cohort 1B is opened for enrollment. 
 
If severe adverse effect (grade 3 or 4 CTCAE) is observed in any cohort we will review with 
MSKCC-DSMC and IRB before continuing with accrual. If  3 patients in cohort 1A do no not show 
acceptable imaging, as described above, we will proceed to cohort 1B. 
 
In cohort 1B, 6 more patients will be enrolled at a higher dose (20mg) for safety and 
pharmacokinetic evaluation.  Serial blood draws will be used to estimate the pharmacokinetic 
profile of the 10 and 20mg 89Zr-DFO-MSTP2109A in this patient population. Pharmacokinetic 
analysis will be performed using a non-compartmental analysis; standard parameters such as 
AUC, clearance, volume of distribution, and Co will be reported. Descriptive statistics will be 
tabulated. If 3 patients in Cohort 1B have antibody negative imaging accrual  will stop. If 4 
patients in cohort 1B have positive imaging we will move to cohort  2 using the best imaging dose 
from cohort IA or 1B.. 
 
Based on pharmacokinetic analysis from cohorts 1A and 1B an optimal time point (based visually 
on optimal image quality for tumor detection and clinically/logistically feasible) will be determined 
for imaging and cohort 2 will enroll up to 15 patients at the dose also determined from cohorts 1A 
or 1B. These patients will undergo a single whole-body scan at the optimal time point. The ability 
of 89Zr-DFO-MSTP2109A to detect tumors will be estimated from this cohort using the proportion 
of antibody-imaging-positive patients (within +/-22% if the true detection rate is 75%). 
 
This study does not intend to find the maximal tolerated dose of DFO-MSTP2109A. This is a 
diagnostic agent that is expected to have low incidence of adverse events.  Patients will be 
monitored closely looking for evidence of adverse events.  Because patients will likely start new 
therapies within 2 weeks of receiving  89Zr-DFO-MSTP2109A  only short term toxicity will be 
evaluated. The safety and tolerability of 89Zr-DFO-MSTP2109A will be assessed using the 
following primary safety outcome measures: Incidence and nature of incidence, nature, and 
severity of adverse events; and change in vital signs and clinical laboratory results. Incidence and 


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severity of adverse events will be summarized with descriptive statistics. 
 
Dosimetry: SUVmax/mean (that can easily be converted to %ID/g) in normal organs of patients 
from Cohort 1A and Cohort 1B will be determined and this data over time will be used to 
determine the residence time in each visualized organ (liver, spleen, kidney and lung), other 
organ will be evaluated if clinically appropriate. The median residence time value will be used in 
OLINDA software to calculate the dosimetry. 
 
14.3 
Secondary objectives 
 
One of our secondary exploratory objectives is to estimate the uptake in tumors. We will present 
lesion-based summary statistics for the uptake adjusted for clustering. Another secondary 
objective is to correlate 89Zr-DFO-MSTP2109A imaging to response to treatment in those patients 
recruited to protocol 11-016 DSTP3086S ADC.  Outcome measures to be correlated include 
those that are outlined in the parent protocol 11-016 and include PSA response, RECIST 
response, presence or absence of new bone scan lesion and progression free survival. We will 
use Kaplan-Meier estimates and 95% confidence intervals to correlate these outcomes with 
imaging response. 
 
15.1 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
 
15.2 
Research Participant Registration 
 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject Eligibility. 
 
Obtain informed consent, by following procedures defined in section entitled Informed 
Consent Procedures. 
 
During the registration process registering individuals will be required to complete a 
protocol specific Eligibility Checklist. 
 
All participants must be registered through the Protocol Participant Registration (PPR) 
Office at Memorial Sloan-Kettering Cancer Center. PPR is available Monday through 
Friday from 8:30am – 5:30pm at 646-735-8000. Registrations must be submitted via the 
PPR Electronic Registration System (http://ppr/). The completed signature page of the 
written consent/RA or verbal script/RA, a completed Eligibility Checklist and other relevant 
documents must be uploaded via the PPR Electronic Registration System. 
 
15.3 
Randomization 
 
This research study does not require randomization procedures. 
 
16.1 
DATA MANAGEMENT ISSUES 
 
A Research Study Assistant (RSA) will be assigned to the study. The responsibilities of the RSA 
include project compliance, data collection, abstraction and entry, data reporting, regulatory 
monitoring, problem resolution and prioritization, and coordinate the activities of the protocol study 
team. 
 
The data collected for this study will be entered into a secure database. Source documentation 
will be available to support the computerized patient record. 
Study personnel will record clinical data in each patient’s source documents (i.e., the patient’s 
medical record). 


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The investigator will maintain adequate and accurate records to enable the conduct of the study  
to be fully documented and the study data to be subsequently verified. After study closure, the 
investigator will maintain all source documents, study-related documents, and the data stored in 
the database used for data collection. Records will be retained and securely stored for a minimum 
of 2 years after the completion of all study activities. 
 
Data will be entered throughout the duration of the trial as patients are enrolled. Accrual is 
expected to last 2 years. 
 
16.2 
Quality Assurance 
 
Regularly scheduled registration reports will be generated to monitor patient accruals and 
the completeness of registration data. Routine data quality reports will be generated to 
assess missing data and inconsistencies. Accrual rates and the extent and accuracy of 
evaluations and follow-up will be monitored periodically throughout the study period, and 
potential problems will be brought to the attention of the principal investigator for 
discussion and action. 
Random-sample data quality and protocol compliance audits will be conducted by the 
study team at least once a year, more frequently if indicated. 
 
16.3 
Data and Safety Monitoring 
 
The data and safety monitoring (DSM) plans at MSKCC were approved by the National 
Cancer Institute in September 2001. The plans address the policies set forth by the NCI in 
the document entitled Policy of the National Cancer Institute for Data and Safety 
Monitoring of Clinical Trials, which can be found at  
http://cancertrials.nci.nih.gov/clinicaltrials. The DSM plans at MSKCC were established 
and are monitored by the Office of Clinical Research. The MSKCC DSM plans can be 
found on the MSKCC Intranet at: http://mskweb5.mskcc.org/intranet/html/70775.cfm. 
 
There are several different mechanisms by which clinical trials are monitored for data, 
safety, and quality. There are institutional processes in place for quality assurance (e.g., 
protocol monitoring, compliance and data verification audits, therapeutic response, and 
staff education on clinical research quality assurance) and departmental procedures for 
quality control, and there are two institutional committees that are responsible for 
monitoring the activities of our clinical trials programs. The committees: Data and Safety 
Monitoring Committee (DSMC) for Phase I and II clinical trials, and the Data and Safety 
Monitoring Board (DSMB) for Phase III clinical trials, report to the MSKCC Research 
Council and Institutional Review Board. 
 
During the protocol development and review process, each protocol will be assessed for 
its level of risk and degree of monitoring required. Every type of protocol (e.g., NIH 
sponsored, in-house sponsored, industrial sponsored, NCI cooperative group, etc.) will be 
addressed, and the monitoring procedures will be established at the time of protocol 
activation. 
 
For this protocol, we will use the following patient safety monitoring plan and monitoring  
for adverse events, in terms of the test performed and their timing relative to injection (see 
Table 1 and 2).  Patient will be observed closely during infusion and serial vital signs will 
be monitored every half hour for at least 2 h or later if the patient remains in the 
department. Patients will be queried for adverse events up to 6-8 days after infusion. 
 
Safety reviews will be performed by the MSKCC-DSMC with yearly review by the IRB. 


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17.1 
PROTECTION OF HUMAN SUBJECTS 
 
This study will be conducted in compliance with the protocol, GCP guidelines established by the 
International Conference on Harmonization, and the ethical standards set forth in the Declaration of 
Helsinki 2004 (available at: www.laakariliitto.fi/e/ethics/helsinki.html). 
 
A limited waiver of authorization will be utilized to effectively screen and track patients in screening, 
however the recruitment process outlined presents no more than minimal risk to the privacy of the 
patients who are screened and minimal protected health information (PHI) will be maintained as part 
of a screening log. 
 
This protocol does not have therapeutic intent and does not offer patients therapeutic benefit. This 
will be clearly conveyed to patients when communicating the potential toxicities/side effects of 
participating in this trial. Participation in the trial is voluntary and there will be no financial benefit (or 
burden) for the patients. Participants will not be charged for 89Zr-DFO-MSTP2109A PET scans, 
whole body probe counts, radiotracer drugs, extra blood draws (to measure radiotracer activity), and 
optional biopsies. 
 
17.2 
Privacy 
 
MSKCC’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure of 
protected health information will be limited to the individuals described in the Research 
Authorization form. A Research Authorization form must be completed by the Principal 
Investigator and approved by the IRB and Privacy Board (IRB/PB). 
 
17.3 
Serious Adverse Event (SAE) Reporting 
 
Any SAE must be reported to the IRB/PB as soon as possible but no later than 5 calendar 
days. The IRB/PB requires a Clinical Research Database (CRDB) SAE report be submitted 
electronically to the SAE Office at sae@mskcc.org. The report should contain the following 
information: 
 
Fields populated from CRDB: 
• 
Subject’s name (generate the report with only initials if it will be sent outside of 
MSKCC) 
• 
Medical record number 
• 
Disease/histology (if applicable) 
• 
Protocol number and title 
 
Data needing to be entered: 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
Relationship of the adverse event to the treatment (drug, device, or intervention) 
• 
If the AE was expected 
• 
The severity of the AE 
• 
The intervention 
• 
Detailed text that includes the following 
o A explanation of how the AE was handled 
o A description of the subject’s condition 
o Indication if the subject remains on the study 
o If an amendment will need to be made to the protocol and/or consent form. 


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The PI’s signature and the date it was signed are required on the completed report. 
 
For IND/IDE protocols: 
The CRDB AE report should be completed as above and the FDA assigned IND/IDE number 
written at the top of the report. If appropriate, the report will be forwarded to the FDA by the 
SAE staff through the IND Office. 
 
17.2.1 
 
SAE Reporting To Genentech: 
 
All written IND Safety Reports submitted to the FDA by the Investigator must also be 
faxed to Genentech Drug Safety: 
• Serious AE reports that are related to the 89Zr-MSTP2109A will be transmitted to Genentech within 
fifteen (15) calendar days of the Awareness Date. 
• Serious AE reports that are unrelated to the 89Zr-MSTP2109A will be transmitted to Genentech 
within thirty (30) calendar days of the Awareness Date. 
 
Investigators must report all SAEs to Genentech within the timelines described above. The completed 
MedWatch/case report should be faxed immediately upon completion to Genentech Drug Safety at: 
 
(650) 225-4682 
OR 
(650) 225-5288 
 
 
17.4 
SAE Recording and Grading 
 
17.3.1 
Recording 
 
The investigator must assess each event to determine if it meets the criteria for 
classification as a serious adverse event (SAE) or serious adverse drug reaction (ADR). 
An SAE/ADR as defined in the Code of Federal Regulations (21CFR312.32) is any event 
that: 
 
• 
Results in death 
• 
Is life-threatening 
• 
Results in inpatient hospitalization or prolongs an existing hospitalization 
• 
Results in persistent or significant disability/incapacity 
• 
Results in congenital anomaly/birth defect 
• 
Is medically significant in the opinion of the investigator 
 
All SAEs that occur any time a patient is on study (i.e., as soon as the informed consent 
has been signed) or within 30 days of the 89Zr-DFO-MSTP2109A scan must be reported, 
regardless of the suspected relationship to 89Zr-DFO-MSTP2109A. Any SAE occurring 
more than 30 days after the 89Zr-DFO-MSTP2109A scan must be reported if a causal 
relationship to 89Zr-DFO-MSTP2109A is suspected. 
 
Because the subjects enrolled in this clinical investigation will be exclusively patients with 
advanced prostate cancer, these patients will typically have received extensive medical 
care before and at the time of enrollment in the study. Such medical care includes 
extensive diagnostic radiological studies, such as x-rays, CT scans, and nuclear  
medicine studies (e.g., bone scans) and, in at least some cases, external beam radiation 
therapy, brachytherapy, or both. The additional radiation doses associated with the 89Zr- 


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DFO-MSTP2109A study will typically represent a small increment in their “lifetime” 
exposures, given the number of clinical studies (CT, bone scan, FDG scan) and that 
many of these patients will have had primary radiation to their prostate or external beam 
radiation to bone. 
 
When accounting for many tests per year, the radiation doses (on the order of 10 rem) lie 
well within the “low-dose” range—well below the threshold doses (typically on the order of 
100 rem or greater) for any known deterministic effects. A detailed description of the 
expected dosimetry from the 89Zr-DFO-MSTP2109A is included (Table 3). The dose of 
89Zr-DFO-MSTP2109A per administration (~5mCi) gives the lowest amount that would be 
consistent with the research goal, namely, biodistribution, metabolism, and 
pharmacokinetics of the compound. 
 
17.3.2 
Grading Severity 
 
All adverse events will be graded for intensity on a scale of 0 to 5. Severity grades will be 
recorded and based on the CTCAE v4.0. 
 
17.3.3 
Attributing Causality 
 
The investigator will evaluate the potential relationship between all clinical AEs, abnormal 
laboratory values, and the 89Zr-DFO-MSTP2109A, and categorize the relationship 
according to the descriptions in Table 5. Abnormal laboratory values of clinical 
significance that were present at baseline and did not change in either severity or 
frequency during the experimental therapy or intervention and/or that can obviously be 
attributed to the underlying disease will be evaluated by the investigator and recorded in 
the “unrelated” category. 
 
 
Table 6. 
Relationship of Adverse Event to 89Zr-DFO-MSTP2109A 
 
Relationship 
Description 
Unrelated 
AE is clearly not related to the 89Zr-DFO- 
MSTP2109A 
Unlikely 
AE is unlikely related to the 89Zr-DFO- 
MSTP2109A 
Possible 
AE may be related to the 89Zr-DFO- 
MSTP2109A 
Probable 
AE is likely related to the 89Zr-DFO- 
MSTP2109A 
Definite 
AE is clearly related to the 89Zr-DFO- 
MSTP2109A 
 
 
Adverse events will be defined graded  using CTCAE V4.0. 
 
 
18.1 
INFORMED CONSENT PROCEDURES 
 
Before protocol-specified procedures are carried out, consenting professionals will explain 
full details of the protocol and study procedures as well as the risks involved to participants 


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prior to their inclusion in the study. Participants will also be informed that they are free to 
withdraw from the study at any time. All participants must sign an IRB/PB-approved consent 
form indicating their consent to participate. This consent form meets the requirements of the 
Code of Federal Regulations and the Institutional Review Board/Privacy Board of this Center. 
The consent form will include the following: 
 
1. The nature and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information. In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
 
19.0 
REFERENCES 
 
Apolo, A. B., N. Pandit-Taskar, et al. (2008). "Novel Tracers and Their Development for the Imaging 
of Metastatic Prostate Cancer." Journal of Nuclear Medicine 49(12): 2031-2041. 
Bander, N. H., M. I. Milowsky, et al. (2005). "Phase I trial of (177)lutetium-labeled J591, a 
monoclonal antibody to prostate-specific membrane antigen, in patients with androgen- 
independent prostate cancer." Journal of Clinical Oncology 23(21): 4591-4601. 
Bander, N. H., E. J. Trabulsi, et al. (2003). "Targeting metastatic prostate cancer with radiolabeled 
monoclonal antibody J591 to the extracellular domain of prostate specific membrane 
antigen." Journal of Urology 170(5): 1717-1721. 
Borjesson, P. K. E., Y. W. S. Jauw, et al. (2006). "Performance of immuno-positron emission 
tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of 
lymph node metastases in head and neck cancer patients." Clinical Cancer Research 12(7): 
2133-2140. 
Borjesson, P. K. E., Y. W. S. Jauw, et al. (2009). "Radiation Dosimetry of Zr-89-Labeled Chimeric 
Monoclonal Antibody U36 as Used for Immuno-PET in Head and Neck Cancer Patients." 
Journal of Nuclear Medicine 50(11): 1828-1836. 
Carrasquillo, J. A., N. Pandit-Taskar, et al. (2011). "(124)I-huA33 Antibody PET of Colorectal 
Cancer." Journal of Nuclear Medicine 52(8): 1173-1180. 
Challita-Eid, P. M., K. Morrison, et al. (2007). "Monoclonal antibodies to six-transmembrane 
epithelial antigen of the prostate-1 inhibit intercellular communication in vitro and growth of 
human tumor xenografts in vivo." Cancer Research 67(12): 5798-5805. 
Dijkers, E. C., T. H. O. Munnink, et al. (2010). "Biodistribution of Zr-89-trastuzumab and PET 
Imaging of HER2-Positive Lesions in Patients With Metastatic Breast Cancer." Clinical 
Pharmacology & Therapeutics 87(5): 586-592. 
Divgi, C. R., N. Pandit-Taskar, et al. (2007). "Preoperative characterisation of clear-cell renal 
carcinoma using iodine-124-labelled antibody chimeric G250 ((124)I-cG250) and PET in 
patients with renal masses: a phase I trial." Lancet Oncology 8(4): 304-310. 


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IRB#:12-178 A(3) 
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Divgi, C. R., N. Pandit-Taskar, et al. (2007). "Preoperative characterisation of clear-cell renal 
carcinoma using iodine-124-labelled antibody chimeric G250 (I-124-cG250) and PET in 
patients with renal masses: a phase I trial." Lancet Oncology 8(4): 304-310. 
Doronina, S. O., B. E. Toki, et al. (2003). "Development of potent monoclonal antibody auristatin 
conjugates for cancer therapy." Nature Biotechnology 21(7): 778-784. 
Francisco, J. A., C. G. Cerveny, et al. (2003). "cAC10-vcMMAE, an anti-CD30-monomethyl auristatin 
E conjugate with potent and selective antitumor activity." Blood 102(4): 1458-1465. 
Gulec, S. A., S. J. Cohen, et al. (2011). "Treatment of Advanced Pancreatic Carcinoma with (90)Y- 
Clivatuzumab Tetraxetan: A Phase I Single-Dose Escalation Trial." Clinical Cancer Research  
17(12): 4091-4100. 
Holland, J. P., E. Caldas-Lopes, et al. (2010). "Measuring the Pharmacodynamic Effects of a Novel 
Hsp90 Inhibitor on HER2/neu Expression in Mice Using (89)Zr-DFO-Trastuzumab." Plos One 
5(1). 
Holland, J. P., V. Divilov, et al. (2010). "(89)Zr-DFO-J591 for ImmunoPET of Prostate-Specific 
Membrane Antigen Expression In Vivo." Journal of Nuclear Medicine 51(8): 1293-1300. 
Holland, J. P., V. Divilov, et al. (2010). "Zr-89-DFO-J591 for ImmunoPET of Prostate-Specific 
Membrane Antigen Expression In Vivo." Journal of Nuclear Medicine 51(8): 1293-1300. 
Holland, J. P., Y. C. Sheh, et al. (2009). "Standardized methods for the production of high specific- 
activity zirconium-89." Nuclear Medicine and Biology 36(7): 729-739. 
Hubert, R. S., I. Vivanco, et al. (1999). "STEAP: A prostate-specific cell-surface antigen highly 
expressed in human prostate tumors." Proceedings of the National Academy of Sciences of 
the United States of America 96(25): 14523-14528. 
Larson, S. M., M. Morris, et al. (2004). "Tumor localization of 16 beta-F-18-fluoro-5 alpha- 
dihydrotestosterone versus F-18-FDG in patients with progressive, metastatic prostate 
cancer." Journal of Nuclear Medicine 45(3): 366-373. 
Milowsky, M. I., D. M. Nanus, et al. (2004). "Phase I trial of yttrium-90-labeled anti-prostate-specific 
membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer." 
Journal of Clinical Oncology 22(13): 2522-2531. 
Morris, M. J., T. Akhurst, et al. (2005). "Fluorodeoxyglucose positron emission tomography as an 
outcome measure for castrate metastatic prostate cancer treated with antimiorotubule 
chemotherapy." Clinical Cancer Research 11(9): 3210-3216. 
Morris, M. J., T. Akhurst, et al. (2002). "Fluorinated deoxyglucose positron emission tomography 
imaging in progressive metastatic prostate cancer." Urology 59(6): 913-918. 
Morris, M. J., C. R. Divgi, et al. (2005). "Pilot trial of unlabeled and indium-111-labeled anti-prostate- 
specific membrane antigen antibody J591 for castrate metastatic prostate cancer." Clinical 
Cancer Research 11(20): 7454-7461. 
Morris, M. J., N. Pandit-Taskar, et al. (2007). "Phase I evaluation of J591 as a vascular targeting 
agent in progressive solid tumors." Clinical Cancer Research 13(9): 2707-2713. 
Nanus, D. M., M. I. Milowsky, et al. (2003). "Clinical use of monoclonal antibody HuJ591 therapy: 
Targeting prostate specific membrane antigen." Journal of Urology 170(6): S84-S88. 
Naruki, Y., J. A. Carrasquillo, et al. (1990). "DIFFERENTIAL CELLULAR CATABOLISM OF IN-111, 
Y-90 AND I-125 RADIOLABELED T101 ANTI-CD5 MONOCLONAL-ANTIBODY." Nuclear 
Medicine and Biology 17(2): 201-207. 
Pandit-Taskar, N., M. J. Morris, et al. (2008). "Antibody mass escalation study in patients with 
castration-resistant prostate cancer using In-111-J591: Lesion detectability and dosimetric 
projections for Y-90 Radioimmunotherapy." Journal of Nuclear Medicine 49(7): 1066-1074. 
Sakamoto, J., H. Kojima, et al. (2000). "Organ-specific expression of the intestinal epithelium-related 
antigen A33, a cell surface target for antibody-based imaging and treatment in 
gastrointestinal cancer." Cancer Chemotherapy and Pharmacology 46: S27-S32. 
Scher, H. I. and G. Heller (2000). "Clinical states in prostate cancer: Toward a dynamic model of 
disease progression." Urology 55(3): 323-327. 
Steffens, M. G., O. C. Boerman, et al. (1997). "Targeting of renal cell carcinoma with iodine-131- 
labeled chimeric monoclonal antibody G250." Journal of Clinical Oncology 15(4): 1529-1537. 


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Zanzonico, P. B., R. Finn, et al. (2004). "PET-based radiation dosimetry in man of F-18- 
fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer." Journal of Nuclear 
Medicine 45(11): 1966-1971. 
 
 
20.0 
APPENDICES 
Appendix A 
ADC 
Antibody drug conjugate 
ADR 
Adverse drug reaction 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANC 
Absolute Neutrophil Count 
AST 
Asparagine aminotransferase 
AUC 
Area under the curve 
BUN 
Blood urea nitrogen 
CBC 
Complete blood count 
cG250 
Chimeric G250 antibody 
CRF 
Case Report Form 
CT 
Computed tomography 
CTCAE 
Common toxicity criteria for adverse events 
DFO 
Desferrioxamine B 
18F 
Fluor-18 
FDG 
Fluorodeoxyglucose 
GCP 
Good Clinical Practice 
IDMC 
Independent Data Monitoring Committee 
IgG1 
Immunoglobulin G1 subclass 
IHC 
Immunohistochemistry 
124I 
Iodine-124 
IND 
Investigational New Drug 
IRB/ PB 
Institutional Review Board/ Privacy Board 
IV 
Intravenous 
KPS 
Karnofsky Performance Scale 
mCi 
milliCurie 
mg 
milligram 
MMAE 
Monomethyl auristatin E 
MRI 
Magnetic resonance imaging 
PET 
Positron emission tomography 
PHI 
Protected Health Information 
PK 
Pharmacokinetics 
PO 
Per os (by mouth) 
PSA 
Prostate-specific antigen 
PSMA 
Prostate Specific Membrane Antigen 
rad 
Radiation absorbed dose 
RECIST 
Response Evaluation Criteria in Solid Tumors 
rem 
Roentgen equivalent man 
ROI 
Region of interest 
SAE 
Serious adverse event 
STEAP1 
Six-transmembrane epithelial antigen of the prostate-1 
SUV 
Standardized uptake value 
WBC 
Whole Body Count 
WBS 
Whole Body Scan 
89Zr 
Zirconium-89 


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MEMORIAL SLOAN-KETTERING CANCER CENTER 
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IRB#:12-178 A(3) 
 
APPENDIX B: 
Karnofsky Performance Status 
 
 
Karnofsky Performance Scale 
 
Condition 
% 
Comments 
Able to carry on normal activity and to work; 
no special care needed. 
100 
Normal; no complaints; no evidence of disease. 
90 
Able to carry on normal activity; minor signs or 
symptoms of disease. 
80 
Normal activity with effort; some signs or 
symptoms of disease. 
Unable to work; able to live at home and care 
for most personal needs; varying amount of 
assistance needed. 
70 
Cares for self; unable to carry on normal activity or 
to do active work. 
60 
Requires occasional assistance, but is able to care for 
most of his personal needs. 
50 
Requires considerable assistance and frequent 
medical care. 
Unable to care for self; requires equivalent of 
institutional or hospital care; disease may be 
progressing rapidly. 
40 
Disabled; requires special care and assistance. 
30 
Severely disabled; hospital admission is indicated 
although death not imminent. 
20 
Very sick; hospital admission necessary; active 
supportive treatment necessary. 
10 
Moribund; fatal processes progressing rapidly. 
0 
Dead