Clinical trial NCT02574455
Conditions: Breast Cancer
Sponsor: Gilead Sciences
Start date: 2017-11-07; Completion date: 2020-12-08
Enrollment: 529 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to compare the efficacy of sacituzumab govitecan to the treatment of physician's choice (TPC) as measured by independently-reviewed Independent Review Committee (IRC) progression-free survival (PFS) in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) previously treated with at least two systemic chemotherapy regimens for unresectable, locally advanced or metastatic disease, and without brain metastasis at baseline.

Detailed description:

Arms: arm 1: Participants will receive sacituzumab govitecan on Days 1 and 8 of a 21-day treatment cycle for up to 29.6 months. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable adverse events (AEs). arm 2: Participants will receive TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent regimen that is selected by the investigator before participant randomization. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable AEs.
Interventions: intervention 1: Sacituzumab govitecan intervention 2: Eribulin intervention 3: Capecitabine intervention 4: Gemcitabine intervention 5: Vinorelbine
Intervention descriptions: intervention 1: 10 mg/kg administered as a slow intravenous (IV) infusion either by gravity or with an infusion pump. Infusion rate for the first 15 minutes will start with 50 mg/hour or less with a subsequent infusion of 100 to 200 mg/hour up to a maximum recommended rate (advanced every 15 to 30 minutes) of 500 mg/hour with a subsequent infusion of 1000 mg/hour. intervention 2: Administered IV over 2 to 5 minutes at a dose 1.4 mg/m\^2 at North American sites and 1.23 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle for up to 15.3 months. Lower doses will be administered on the same schedule to participants with moderate hepatic impairment (ie, Child-Pugh B; 0.7 mg/m\^2 and 0.67 mg/m\^2 for North American and European sites, respectively). intervention 3: 1000 to 1250 mg/m\^2 will be administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period for up to 10.6 months. intervention 4: 800 to 1200 mg/m\^2 will be administered IV over 30 minutes on Days 1, 8, and 15 of a 28-day cycle for up to 8.1 months. intervention 5: 25 mg/m\^2 will be administered as a weekly IV injection over 6-10 minutes for up to 11.5 months. Vinorelbine will not be allowed as TPC for any participant with Grade 2 neuropathy.

Protocol documents:
SAP_002.pdf: 
 
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IMMUNOMEDICS IMMU-132-05 STATISTICAL ANALYSIS PLAN 
 
Full Title of Study 
An International, Multi-Center, Open-Label, Randomized Phase III 
Trial of Sacituzumab Govitecan versus Treatment of Physician Choice 
in Patients with Metastatic Triple-Negative Breast Cancer Who 
Received at Least Two Prior Treatments 
Protocol Number 
IMMU-132-05 
IND Reference  
Number 
122694 
Version 
12.0 
Date 
April 10, 2020 
Sponsor Name 
Immunomedics, Inc. 
Sponsor Address 
300 The American Road, Morris Plains, NJ 07950 
 
 
 
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Revision History 
Revision Date 
Description of Change 
4.0 
May 5, 
2017 
Clarification of specific dosing regimens for the 4 agents in the treatment of 
physician choice (TPC) arm of the trial  
5.0 
July 31, 
2017 
To align with Revision 2 of  Amendment #2: revised  the schedule of CT or 
MRI scans, added stratification factor for presence of brain metastases, and 
revised language describing  dose modifications of treatment of physician 
choice if too toxic. 
6.0 
February 
8, 2018 
To align with Global Amendment #3, to increase sample size, clarify 
patient population, clarify analyses sub-population analyses.  
7.0  
May 16, 
2018 
To align with Global Amendment #4, to increase sample size, clarify 
primary and secondary patient populations, align sample size calculations 
with analysis populations, clarify analyses for multiple endpoints. 
November 
28, 2018 
Section 3.4.1: PFS censoring rule, letter ©, says now “progress or die”.  
Section 5.2, at end, and section 5.4.3, at end, clarify significance level to 
use for final OS analysis in ITT population.  
Section 5.8.5 added for imputation of missing or incomplete dates for AEs 
and Concomitant Medications 
 
 
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Revision History 
Revision 
Date 
Description of Change 
8.0 
April 
22, 
2019 
The SAP update Version 8.0 reflects a major improvement to the SAP in 
clarity, detailedness, organization and coherence.  
The SAP update is completed after the planned interim was cancelled per 
communication with FDA but prior to database lock or any unblinding of 
data.  The aim of the update is to provide sufficient details to ensure 
accurate and correct execution of statistical programming of tables, 
figures and listings in implementing this plan, improve clarity and 
coherence of the document to both internal and external stakeholders, as 
well as correcting some apparent errors and inconsistencies. Some new 
analyses were also added to ensure comprehensive and robust data 
analyses and interpretation.  To this end, text was significantly added, 
revised, consolidated or reorganized in appropriate sections.  However, 
the specifics of study critical details such as those concerning definitions 
of primary and key secondary endpoints, primary and key secondary 
analyses methods and analysis populations, multiplicity control, 
significance levels for testing PFS and OS endpoints are not changed.  
Notable changes are delineated in the Revision History section (Version 
8.0). 
Below is a detailed list of all notable changes:  
General:  
Formatting and correction of grammatical errors in the overall document 
were updated and corrected throughout.   
Page 1: Changed Protocol Title to be consistent with the Protocol 
Section 3 Study Objectives and Endpoints 
Removed paragraphs that are either repetitive or with inaccurate citations 
of study procedures from the protocol in the Overview of Study and 
Clinical Trial Endpoints sections.  
Clarified description of Independent Review Charter for tumor scan 
images. Updated reference to FDA guidelines on cancer trial endpoints 
to the latest versions: Clinical Trials Endpoints for the Approval of 
Cancer Drugs and Biologics (December 2018) and Clinical Trial 
Endpoints for the Approval of Non-Small Cell Lung Cancer Drugs and 
Biologics (April 2015) 
3.4 Clinical Trial Endpoints 
For the primary endpoint of PFS, “without prior missing assessments” 
was removed as it is clarified in the censoring rule ©(c). Added a table to 
clarifying censoring rule for PFS.  All references to sensitivity analyses 
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of PFS are referred to be described in the “Section 5.11.3 Sensitivity 
Analysis of PFS.” 
Section 3.4.2 Definition of OS 
“not known to have died at last follow-up” was changed to “without 
documentation of death” as the former is contained by the latter.  The 
sentence of “Patients are censored at the date of initiation of therapy 
(Day 1) if no additional data are obtained.” was removed, as this 
criterion may not apply due to some randomized patients not receiving 
any dose of drug, and this scenario is accounted for by the rule for 
censoring. 
Section 3.4.3 was added to fully define Time to Progression (TTP) and 
censoring rules. 
Section 3.4.4, definitions regarding ORR, clinical benefit rate, TTR for 
only responders (CR or PR), were added, refined or clarified and 
censoring rules were added for DOR. 
Section 3.4.5, the definition of TEAE was clarified, and definitions were 
consolidated in this section, and reference to analyses were moved to 
later sections in the SAP.  
 
 
 
Section 3.4.7 Title of Physical Function Evaluation was changed to 
Patient Reported Outcome, and the sentence of analyses was removed as 
it is described in the analyses section. 
Section 4, Analyses Population  
Removed “Efficacy Analyzable Population” from this section as it is 
specific to the analyses on ORR, which is explained in the respective 
section. The definition of the BM-ve population was clarified to be 
defined by randomization. 
.  
The diagram showing various analyses population was removed, instead, 
a table was added in this section to provide “An overview of Analyses 
and Analysis Populations” that identified and clarified which analysis 
will be conducted in which analysis population.  
Section 5.1 Determination of Sample Size 
Clarified the 315 PFS events as defined for the primary analysis in the 
primary analysis population of patients without brain metastases (BM-ve 
population). 
Section 5.2 Interim analysis 
Removed reference to interim futility analysis, and consolidated 
paragraphs associated  with the multiplicity control section. There was 
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an apparent error with the citation of Lan-DeMets spending function. 
The previous version cited the formula at 1-sided alpha at 0.025 level but 
the formula was apparently mis-typed and corrected: the formula of Lan-
DeMets alpha spending function at 2-sided alpha level (0.05) is standard; 
this typographical error was corrected.  
Section 5.3 Data and Safety Monitoring Committee (DSMC) was 
removed as this text isnot in scope for this analysis plan.  
Section 5.3 title changed from “Statistical Methods” to “Overview of 
General Approaches”, with some clarification and consolidation in the 
section.  
Statistical Analyses sections (5.4 – 5.14):These sections underwent 
major consolidation with additional details, which were reorganized into 
subsections by topics, as below, some of which were newly added: 5.4 
Patient Accrual and Eligibility, 5.5 Demographics, 5.6 Baseline Disease 
Characteristics, 5.7 Patient Disposition, 5.8 Protocol Deviation, 5.9 Prior 
Anticancer Therapy, Prior and Concomitant Medications. 
5.10 Exposure to Study Therapies 
This section is newly added along with additional details, the most 
prominent one is the algorithm to calculate Relative dose intensity.  
5.11.1 Multiplicity Control 
Clarification and consolidation of text only. A diagram of the testing 
procedure is added to illustrate the scenario.  
5.11.2 Primary Analysis for Progression-Free Survival (PFS, primary 
endpoint) 
Clarification of text, along with specifying the method for 95% 
confidence interval of median PFS, and the addition of milestone PFS 
rates.  
5.11.3 Sensitivity Analysis of PFS 
The original SAP proposed some suggested sensitivity analyses based on 
FDA guideline (Sensitivity Analyses #2, #3 and #4), but the censoring 
rules were not sufficiently detailed. Therefore, this section underwent 
significant editing to provide clarity for both operational purpose and 
review purpose.  A table to compare various sensitivity analyses was 
added in the table, and new sensitivity analyses were added (Sensitivity 
Analyses #1 and Analyses #5) 
5.11.4 OS analysis  
The method part of the section is removed as it is identical to the primary 
PFS analysis, and replaced by text pointing this out. (This same change 
is also applied to Section 5.11.5 Time to Progression). Added milestone 
rates were added at 12, 18 and 24 months. 
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5.11.6 Objective Response Rate and Clinical Benefit Rate 
The method used to compare ORR originally “ was “A Chi-square test 
will be used to compare the difference in the treatment groups in regards 
to ORR; if the assumptions for the Chi-square test are not valid, 
a ’Fisher’s Exact test will be”used.” Since this is a stratified randomized 
trial, the Cochran-Mantel-Haenszel is more appropriate to be used. The 
Clinical Benefit Rate to this section as well as analyses similar to ORR. 
5.11.7 Time to Response (TTR) and Duration of Response (DOR)  
TTR will be summarized by descriptive statistics instead of KM 
analyses.  The KM analysis on this endpoint is not considered necessary. 
The summary of DOR greater than or equal to a timeline including 3 
months, 6 months, 9 months and 12 months was added. 
5.11.8 Patient Reported Outcome 
 
Clarified the analysis population of this endpoint. 
5.11.9 Other Analyses and Listings 
Added a number of graphical analyses and listings that were not 
specified in other sections. 
5.11.10 Subgroup Analyses  
This section has been added to provide the pre-specified subgroup 
analyses that will be done on the three efficacy endpoints to evaluate the 
robustness of the efficacy.  
 
 
 
  
5.12 Safety Analyses 
This section underwent significant change to provide organization and 
clarity, including lists of all AE summary tables and listing, and AE 
summaries by subgroup analysis.  
5.12.2 Adverse Events of Special Interest (AEOSI) 
This is a new section added to address the summary of AEs of Special 
Interest, including definitions of AEOSI and summary table of them.  
5.12.3 – 5.12.7 
Other safety summary analyses were organized by topic into 5.12.3 
Death, 5.12.4 Vital Sign, 5.12.5 Electrocardiograms and 5.12.6 Clinical 
Laboratory Evaluations, 5.12.7 Physical Exam and Pregnancy Test. The 
previous version had limited details and references to some of these 
analyses.  
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6.0 References 
Added a reference that includes methods for testing milestone OS rates: 
Klein JP, Logan B, Harhoff M, Andersen PK. (2007). Analyzing survival 
curves at a fixed point in time. Stat Med. 2007 Oct 30; 26(24):4505-19. 
Appendix 1: Response Evaluation Criteria in Solid Tumors (RECIST) 
1.1 was removed as it was copied from the RECIST 1.1 criteria and 
considered not necessary to be included in the SAP.  
9.0 
August 
26, 
2019 
Section 5.11.1 Multiplicity Control: the wording of the bottom right box 
of the diagram was chang“d to “OS (final) in ITT, 2-sided Lan-DeMets 
alpha adjusted at”final” per FDA feedback 
10.0 
April 
06, 
2020 
Section 5.11.1 Multiplicity Control: revised due to changes in the timing 
of analyses as a result from DSMC recommendation and discussions 
with FDA on April 2nd, 2020.  
Section 5.11.9 Added additional language and analyses to address impact 
on trial data due to the outbreak of the COVID-19 pandemic. 
A few minor corrections of typos and misspellings on page 24, page 29 
and Page 35; corrected the mis-directed references to appendix on Page 
16 and Page 19. 
11.0 
Apirl 
08, 
2020 
Per FDA comment dated April 7, 2020, “In the SAP, you should specify 
the number of PFS events that will now be used for the final (and only) 
analysis and clarify the alpha level that will be used for this analysis”, 
section 5.11.1 is revised.   
12.0 
April 
10, 
2020 
Per FDA request dated April 9, 2020, “You should clarify and justify the 
alpha that will be transferred to the final (and only) OS analysis. Further, 
you should clearly specify how the rest of the testing hierarchy (PFS in 
ITT and OS in ITT) will be handled with respect to timing and alpha-
levels.”, section 5.11.1 is updated.  
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Approvals 
Printed Name 
Signature 
 
 Biostatistics 
[See appended signature page] 
 
 Clinical Development 
 
[See appended signature page] 
 
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TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS.....................................................................................12 
2. 
INTRODUCTION ......................................................................................................14 
3. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................15 
3.1. 
Overview of Study ......................................................................................................15 
3.2. 
Study Objectives: Primary ..........................................................................................16 
3.3. 
Study Objectives: Secondary ......................................................................................16 
3.4. 
Clinical Trial Endpoints ..............................................................................................16 
3.4.1. 
Progression-free Survival (PFS) .................................................................................16 
3.4.2. 
Overall Survival (OS) .................................................................................................18 
3.4.3. 
Time to Progression (TTP) .........................................................................................18 
3.4.4. 
Objective Response Rate (ORR), Clinical Benefit Rate (CBR), Time to 
Response, Duration of Response ................................................................................19 
3.4.5. 
Safety Endpoints .........................................................................................................20 
 
 
3.4.7. 
Patient-reported outcomes ..........................................................................................20 
4. 
POPULATIONS FOR ANALYSIS ...........................................................................21 
4.1. 
Screened Population ...................................................................................................21 
4.2. 
Intent-to-Treat (ITT) Population .................................................................................21 
4.3. 
ITT Population Without Brain Metastases (BM-ve Population) ................................21 
4.4. 
Safety Population ........................................................................................................21 
 
 
5. 
STATISTICAL METHODS AND ANALYSES .......................................................23 
5.1. 
Determination of Sample Size ....................................................................................23 
5.2. 
Interim analysis ...........................................................................................................23 
5.3. 
Overview of General Approaches ..............................................................................24 
5.4. 
Patient Accrual and Eligibility ....................................................................................24 
5.5. 
Demographics .............................................................................................................24 
5.6. 
Baseline Disease Characteristics ................................................................................24 
5.7. 
Patient Disposition ......................................................................................................25 
5.8. 
Protocol Deviation ......................................................................................................25 
5.9. 
Prior Anticancer Therapy, Prior and Concomitant Medications ................................25 
5.10. 
Exposure to Study Therapies ......................................................................................26 
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5.11. 
Efficacy Analysis ........................................................................................................26 
5.11.1. 
Multiplicity Control ....................................................................................................26 
5.11.2. 
Primary Analysis for Progression-Free Survival (PFS, primary endpoint) ................29 
5.11.3. 
Sensitivity Analysis of PFS ........................................................................................29 
5.11.4. 
Overall Survival ..........................................................................................................33 
5.11.5. 
Time to Progression ....................................................................................................33 
5.11.6. 
Objective Response Rate and Clinical Benefit Rate ...................................................33 
5.11.7. 
Time to Response (TTR) and Duration of Response (DOR) .....................................33 
5.11.8. 
Patient Reported Outcome ..........................................................................................33 
5.11.9. 
Other Analyses and Listings .......................................................................................33 
5.11.10. 
Subgroup Analyses .....................................................................................................34 
 
 
5.12. 
Safety Analyses ..........................................................................................................35 
5.12.1. 
Adverse Events ...........................................................................................................36 
5.12.2. 
Adverse Events of Special Interest (AEOSI) ..............................................................38 
5.12.3. 
Death ...........................................................................................................................38 
5.12.4. 
Vital Sign ....................................................................................................................38 
5.12.5. 
Electrocardiograms .....................................................................................................39 
5.12.6. 
Clinical Laboratory Evaluations .................................................................................40 
5.12.7. 
Physical Exam and Pregnancy Test ............................................................................40 
 
 
 
 
 
 
 
 
5.15. 
Data Handling Rules ...................................................................................................41 
5.15.1. 
Conversions from Days to Years, Months or Weeks .................................................41 
5.15.2. 
Computation of Duration ............................................................................................41 
5.15.3. 
Missing normal ranges for laboratory parameters ......................................................41 
5.15.4. 
Non-Numeric Laboratory Results and Calculation of Normal Ranges ......................41 
5.15.5. 
Imputation of Missing or Incomplete Dates ...............................................................42 
5.16. 
Statistical Software used in data analysis ...................................................................43 
6. 
REFERENCES ...........................................................................................................44 
 
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LIST OF TABLES 
Table 1: 
Censoring rules for the endpoint of Progression-Free Survival .................................17 
Table 2: 
Censoring rules for the endpoint of Time to Progression ...........................................18 
Table 3: 
Censoring rules for the endpoint of Duration of Response ........................................19 
Table 4: 
An overview of Analyses and Analysis Populations ..................................................22 
Table 5: 
Sensitivity Analyses of PFS and Corresponding Censoring Rules ............................31 
Table 6: 
Definitions of Adverse Events of Special Interest ......................................................38 
 
 
 
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1. 
LIST OF ABBREVIATIONS 
 
Abbreviation 
Full Term 
AE 
adverse event 
AEOSI 
adverse event of special interest 
ADC 
antibody-drug conjugate 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
βHCG 
beta human chorionic gonadotropin 
BM-ve 
brain metastases negative (no brain metastases at baseline/randomization) 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CDC 
Complementary-dependent cytotoxicity 
CDR 
complementarity-determining region 
Cmax 
Maximum concentration 
CNS 
central nervous system 
CR 
complete response 
CRF 
case report form 
CTCAE 
common terminology criteria for adverse events 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
GI 
gastrointestinal 
HIV 
human immunodeficiency virus 
ICH 
International Committee on Harmonization 
IgG 
immunoglobulin G 
IND 
Investigational New Drug 
IRB 
institutional review board 
IRC 
Independent Review Committee 
IULN 
institutional upper limit of normal 
LA 
Locally advanced 
LDH 
lactate dehydrogenase 
mAb 
monoclonal antibody 
MTD 
maximum tolerated dose 
NSAE 
non-serious adverse event 
NCI 
National Cancer Institute 
NSAID 
non-steroidal anti-inflammatory drug 
OR 
 
Objective Response, OR = CR + PR 
 ORR 
Objective (overall) Response Rate 
OS 
Overall survival 
PD 
Progressive disease 
PFS 
Progression-free survival 
PK 
pharmacokinetics 
PR 
partial response 
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T1/2 
Elimination phase half-life 
TPC 
Treatment of physician’s choice 
RBC 
red blood cell 
SAE 
serious adverse event 
Trop-2 
Trophoblastic cell-surface antigen 
TNBC 
Triple-Negative Breast Cancer 
TTP 
time to progression 
WBC 
white blood cell 
PFS 
progression free survival 
OS 
Overall Survival 
ORR 
Overall Response Rate 
TPC 
treatment of physician choice 
QOL 
Quality Of Life 
 
 
 
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2. 
INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the proposed statistical analysis of the study 
entitled: “An International, Multi-Center, Open-Label, Randomized Phase III Trial of 
Sacituzumab Govitecan vs. Treatment of Physician Choice in Patients with Locally Advanced or 
Metastatic Triple-Negative Breast Cancer Who Received at Least Two Prior Treatments.” 
The purpose of this document is to ensure the credibility of the study outcomes by pre- 
specifying the statistical approaches and data handling conventions for key analyses.  One focus 
of these analyses is the evaluation of the primary endpoint , Progression-Free Survival (PFS) as 
determined by an independent centralized blinded assessment (Independent Review Committee 
IRC). This PFS analysis will be performed on the patients in the intent-to-treat (ITT) population 
who do not have brain lesions at baseline, and will serve as gatekeeper for additional analyses. 
The primary analysis population will be labelled throughout as the brain-metastases negative 
(BM-ve) population. The overall 0.05 level of significance for the additional analyses will be 
maintained by specifying a hierarchy of endpoints to establish an order in which endpoints will 
be tested. If the PFS analysis in the BM-ve population rejects the null hypothesis (the survival 
distribution of PFS in the sacituzumab govitecan arm and the treatment-of-physician-choice arm 
are not statistically different) then further analyses in the testing hierarchy can be performed. 
Otherwise these analyses will not be done. The order of the testing hierarchy after the PFS 
analysis in the BM-ve population is: 
 Overall survival (OS) in the BM-ve population; 
 PFS in the ITT population; 
 OS in the ITT population. 
If fewer than 30 cases of brain metastasis are enrolled, then analyses based on the ITT population 
will be removed from the testing hierarchy.  
Other comparisons to analyze are: PFS as determined by the investigator, Time to Progression 
(TTP), Objective Response Rate (ORR) determined by investigator and by central review, 
Duration of Response, Time to Onset of Response, Quality of Life, safety including adverse 
events, safety laboratories and evaluations, incidence of dose delays and dose reductions, and 
discontinuation of treatment due to adverse event between two treatment groups.  The analyses 
of all endpoints will be described, the populations for analysis defined, and the rules specified for 
“data handling” relevant to undertaking all the analyses. 
 
 
To comply with regulatory electronic submission guidelines, listings of all clinical data will be 
submitted as electronic data sets.  Specific listings will be generated as described. 
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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Overview of Study 
This is a Phase III, randomized, open-label, multicenter (up to 150 centers) study of IMMU-132 
(sacituzumab govitecan) in locally advanced or metastatic TNBC patients who are refractory or 
relapsing after at least 2 prior standard chemotherapy regimens for unresectable, locally 
advanced or metastatic breast cancer, and these regimens will qualify regardless of triple-
negative status at the time they were given. There is no upper limit in the number of prior 
therapies. Earlier adjuvant or neoadjuvant treatment for more limited disease will qualify as one 
of the required prior regimens if the development of unresectable, locally advanced or metastatic 
disease occurred within a 12-month period of time after completion of chemotherapy. All 
patients must have been previously treated with taxane regardless of disease stage (adjuvant, 
neoadjuvant or advanced) when it was given. Patients who have contra-indications or are 
intolerant to taxanes are eligible provided that they received at least one cycle of a taxane and 
showed contra-indications or intolerance during or at the end of that cycle. For patients with a 
documented germ-line BRCA1/BRCA2 mutation who received an approved PARP inhibitor, the 
PARP inhibitor can be used to meet the criteria for one of two prior standard of care 
chemotherapies. 
Approximately Four-hundred eighty-eight (488) patients from up to approximately 150 centers, 
including sites in North America, Europe and potentially elsewhere will be randomized 1:1 to 
receive either sacituzumab govitecan (IMMU-132) at a dose level of 10 mg/kg on days 1 and 8 
of a 21-day cycle or Treatment of Physician Choice (TPC). 
For patients in TPC arm, one of the following treatments will be determined before 
randomization, administered for metastatic breast cancer as per NCCN guidelines below or local 
standard of care if too toxic: 
1. Eribulin (1.4 mg/m2 intravenously on Days 1 and 8 of a 21-day cycle North America 
sites, 1.23 mg/m2 intravenously on Days 1 and 8 of a 21-day cycle for European sites), 
2. Capecitabine (1000-1250 mg/m2 orally twice daily for 2 weeks followed by a 1 week 
rest period given as a 21-day cycle), 
3. Gemcitabine (800-1250 mg/m2 intravenously on Days 1, 8 and 15 of a 28-day cycle),     
or 
4. Vinorelbine (25 mg/m2 intravenously on Day 1 weekly) treatment. 
Stratification and Randomization Scheme 
At registration, patients will be randomized to receive either sacituzumab govitecan at a dose 
level of 10 mg/kg on days 1 and 8 of a 21-day cycle or TPC. 
Patients will be stratified at randomization by means of an interactive web-based response 
system (IWRS) according to the following classifications: 
 Number of prior treatments (2-3 vs >3) 
 Presence of known brain metastases at study entry (yes vs no) 
 North America vs Rest of World 
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3.2. 
Study Objectives: Primary 
The primary objective of this study is to compare the efficacy of sacituzumab govitecan to the 
Treatment of Physician’s Choice (TPC) as measured by independently reviewed progression-free 
survival (PFS) in patients with locally advanced or metastatic TNBC previously treated with at 
least two systemic chemotherapy regimens for unresectable, locally advanced or metastatic 
disease, and without brain metastasis at baseline. 
3.3. 
Study Objectives: Secondary 
The secondary objectives of the study are to compare between the two treatment groups for: 
 PFS for the ITT population 
 Overall survival (OS) in both the ITT population and in the subgroup with brain 
metastasis. 
 Independently-determined Objective Response Rate (ORR), duration of response and 
time to onset of response according to RECIST 1.1 criteria 
 Quality of life 
 Safety, including adverse events, safety laboratories and evaluations, incidence of 
dose delays and dose reductions, and treatment discontinuations due to adverse events 
 
 
 
 
 
3.4. 
Clinical Trial Endpoints 
3.4.1. 
Progression-free Survival (PFS) 
PFS will be measured by an independent centralized and blinded group of radiology experts 
(IRC) who will be assessing tumor response using RECIST 1.1 criteria. The procedures for how 
tumor scan images are received, handled, stored and how the independent radiology review is 
performed are described in an Independent Review Charter and can be available upon request. 
FDA definitions and guidance as described in Guidance for Industry: Clinical Trial Endpoints for 
the Approval of Cancer Drugs and Biologics (December 2018) and Clinical Trial Endpoints for 
the Approval of Non-Small Cell Lung Cancer Drugs and Biologics (April 2015) are referenced 
in relevant endpoint definitions.  
PFS will be defined as the time from randomization until objective tumor progression or death, 
whichever comes first. The date of progression will be the earliest time when any tumor 
progression is observed based on RECIST 1.1. It will be the date of the last observation or 
radiological assessment of target lesions that shows a predefined increase (20%+) in the sum of 
the target lesion measurements or the appearance of new non-target lesions. 
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The following censoring rnles will be applied to the primaiy analysis of PFS: 
a. A patient who dies dming follow-up period for survival without documented 
progressive disease will be considered to have an event for PFS analysis. 
b. Patients who do not have progression and are alive will be censored at last date 
of radiographic assessment without documented progressive disease. 
c. Patients in the follow-up period for progression that progress or die following more 
than one missed scheduled visit of scheduled assessment interval as defined in the 
protocol will be censored at the last date of radiographic assessment without 
documented progressive disease. 
d. Patients in the follow-up period for progression who receive alternative anticancer 
treatment before documented progressive disease will be censored at the last date of 
radiographic assessment without documented progressive disease prior to receiving 
alternative anticancer treatment. 
e. Patients without baseline tumor assessments or without additional follow-up data 
will be censored at the date of randomization. However, if such a patient dies no later 
than the time of the second scheduled assessment as defined in the protocol, this 
patient will be considered to have an event at the date of death. 
Calculation and censoring rnles of the primary endpoint of PFS ai·e also surmnai·ized in Table 1. 
Table 1: 
Censoring rules for the endpoint of Progression-Free Survival 
Outcome 
Date ofEvent/Censoring1 
No adequate response assessment afte1· randomization 
Died prior to second scheduled assessment 
PD 
Date of death 
Did not die or died after missing 2 or more 
Censor 
Date of randomization 
scheduled assessments 
Continued scheduled response assessments until objective PD or death 
PD at scheduled assessment, or prior to 
PD 
Date of objective PD 
missing 2 scheduled successive 
assessments 
Death betv.•een scheduled assessments, or 
PD 
Date of death 
prior to missing 2 scheduled successive 
assessments 
PD or death after missing 2 or more 
Censor 
Date oflast adequate response assessment before 
scheduled assessments 
missed ones 
Continued scheduled response assessments without objective PD 01· death 
Initiated other anti-cancer treatment 
Censor 
Date oflast adequate response assessment without 
documented progression prior to starting other anti-
cancer treatment 
No objective PD or death 
Censor 
Date oflast adequate response assessment 
1 Adequate response assessment was defined as a response assessment other than 'not assessed' or 'not evaluable'. If 
progression was based on the sum of target lesion measurements at different time points, the last measurement date was to 
be used as the date of progression. For progression based on new or non-target lesions considered unequivocal 
progression, the earliest date when progression was detected was to be used as the date of progression. 
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The primaiy analysis of PFS will be based on the assessment of the central reviewer in the brain-
metastases negative (BM-ve) population; additional sensitivity analyses will be described in 
Section 5.11.3 Sensitivity Analysis of PFS. 
3.4.2. 
Overall Survival (OS) 
Overall survival is measmed from the date of randomization to death from any cause. Patients 
without documentation of death ai·e censored on the date they were last known to be alive. 
3.4.3. 
Time to Progression (TTP) 
TTP is defined as the time from randomization until objective tumor progression; TTP does not 
include deaths. The censoring rnles of PFS apply to TTP, except that death events are censored, 
either at the time of death or at the date of last adequate response assessment. Censoring rnles for 
TTP are described in Table 2. 
Table 2: 
Censoring rules for the endpoint of Time to Progression 
Case 
Outcome 
Date ofEvent/Censoring1 
No adequate response assessment after randomization 
Died prior to second scheduled 
Censor 
Date of death 
assessment 
Did not die or died after missing 2 or 
Censor 
Date of randomization 
more scheduled assessments 
Continued scheduled response assessments until objective PD or death 
PD at scheduled assessment, or prior 
PD 
Date of objective PD 
to missing 2 scheduled successive 
assessments 
Death betv.•een scheduled 
Censor 
Date of death 
assessments, or prior to missing 2 
scheduled successive assessments 
PD or death after missing 2 or more 
Censor 
Date of last adequate response assessment before 
scheduled assessments 
missed ones 
Continued scheduled response assessments without objective PD 0 1· death 
Initiated other anti-cancer treatment 
Censor 
Date of last adequate response assessment without 
documented progression prior to starting other anti-
cancer treatment 
No objective PD or death 
Censor 
Date of last adequate response assessment 
I Adequate response assessment was defined as a response assessment other than 'not assessed' or 'not evaluable'. If 
progression was based on the sum of target lesion measurements at different time points, the last measurement date was to 
be used as the date of progression. For progression based on new or non-target lesions considered unequivocal 
progression, the earliest date when progression was detected was to be used as the date of progression. 
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3.4.4. 
Objective Response Rate (ORR), Clinical Benefit Rate (CBR), Time to Response, 
Duration of Response 
Objective tumor response will be evaluated from CT scans ( or MRI studies) using RECIST 1.1 
criteria. Using these criteria, the Best Overall Response (BOR) of patients will be classified 
based on tumor response into the categories of complete response (CR), paiiial response (PR), 
stable disease (SD), progressive disease (PD), or not evaluable (NE). Tumor response will be 
assessed by both IRC assessment and investigator assessments. Although the study requires 
measurable disease at baseline based on investigator assessment, the IRC assessments may 
detennine othe1wise for some patients (that is, non-measurable disease at baseline), and 
therefore, an additional catego1y of "Non-CR/Non-PD" is also added for IRC assessed results. 
The endpoint of ORR will be defined as the percentage of the overall best response as CR or PR, 
relative to the size of population under evaluation. 
In addition to ORR, clinical benefit rate (CBR) is defined as those patients with best response as 
CR or PR or else SD (and Non-CR/Non-PD in the case of non-measurable disease at baseline for 
IRC assessed results) with a duration of at least 6 months. For SD subjects, the duration of SD is 
defined as the time from randomization to the first documentation of PD/death or to the last 
adequate response assessment according to the censoring rnle of PFS (Table 1). Details of 
response assessment according to RECIST 1.1 are reflected in the Appendix 6 of the protocol. 
Time to onset of objective response (CR or PR) based on the central reviewer will be calculated 
for objective responders as the time from randomization to the first documentation of response, 
for both IRC and investigator assessed results. 
For patients experiencing response ( a best overall response of CR or PR), duration of objective 
response will be calculated based on the number of days between the first date showing a 
documented response of CR or PR and the date of progression or death. Patients who do not 
progress or die after response will be censored, and the censoring rnles as described in Table 3 
will apply. DOR will be calculated based on both the central IRC and local investigator assessed 
results. 
Table 3: 
Censoring rules for the endpoint of Duration of Response 
Case 
Outcome 
Date ofEvent/Censoring1 
Subsequent PD 01· death after response 
PD at scheduled assessment, or prior 
DOR ended 
Date of objective PD 
to missing 2 scheduled successive 
assessments 
Death betv.•een scheduled 
DOR ended 
Date of death 
assessments, or prior to missing 2 
scheduled successive assessments 
PD or death after missing 2 or more 
Censor 
Date of last adequate response assessment before 
scheduled assessments 
missed ones 
Response without subsequent objective PD 01· death 
Initiated other anti-cancer treatment 
Censor 
Date of last adequate response assessment without 
documented progression prior to starting other anti-
cancer treatment 
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3.4.5. 
Safety Endpoints 
Safety and tolerability will be evaluated based on adverse events, standard safety laboratories 
(CBC with differential and platelet count, serum chemistries, and urinalysis), physical 
examination, EKG, and vital signs.   
Treatment-emergent adverse events (TEAEs) are defined as any AEs that begin or worsen on or 
after the start of study drug through 30 days after the last dose of study drug. Adverse events will 
be coded using the MedDRA system based on preferred terms and system organ class (SOC). 
Adverse events and selected laboratory parameters will be classified for severity using NCI 
CTCAE (v4.03 or later) toxicity grades. Non-numeric components of laboratory grading 
algorithm (such as a criterion requiring hospitalization) will not be included in the grade 
calculations. Only TEAEs will be summarized and will be referred to as AEs hereafter.   
 
 
 
 
 
 
 
 
 
 
 
3.4.7. 
Patient-reported outcomes  
Patient-reported outcomes evaluation will be based on the EORTC-QLQC30 instrument to 
evaluate all patients at baseline, the beginning of every cycle, and the final study visit.  
No objective PD or death 
Censor 
Date of last adequate response assessment 
1  Adequate response assessment was defined as a response assessment other than 'not assessed' or 'not evaluable'. If 
progression was based on the sum of target lesion measurements at different time points, the last measurement date was to 
be used as the date of progression. For progression based on new or non-target lesions considered unequivocal 
progression, the earliest date when progression was detected was to be used as the date of progression. 
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4. 
POPULATIONS FOR ANALYSIS 
The following analyses populations are defined and used for relevant safety, efficacy, 
 
4.1. 
Screened Population 
The screened population is defined as all patients who have signed an informed consent and 
participated in screening procedures at the investigative site to assess eligibility. 
4.2. 
Intent-to-Treat (ITT) Population 
The ITT population is all patients who have been randomized to the trial. Patients are assigned to 
treatment arms based on what they were randomized to receive. This population is used for 
efficacy analyses after the primary endpoint has been tested in the primary analysis population of 
subjects without brain metastases. 
4.3. 
ITT Population Without Brain Metastases (BM-ve Population) 
The BM-ve population is all ITT patients without brain metastases labelled throughout as the 
BM-ve population, defined as all randomized patients who were randomized to the strata of no 
baseline brain metastasis at the time of randomization. 
4.4. 
Safety Population 
All patients administered at least one dose of IMMU-132 or TPC will be included in the Safety 
Population. Safety endpoints will be analyzed using the safety population. 
 
 
 
 
 
  
 
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Table 4: 
An overview of Analyses and Analysis Populations 
Analysis Catego1y 
Enrollment and 
Eligibility 
Demographics 
Baseline Disease 
Characteristics 
Patient Disposition 
Protocol Deviation 
Prior Anticancer 
Therapy, P1ior and 
Concomitant 
Medications 
Exposure to Study 
Therapies 
Efficacy on primruy 
endpoint (IRC assessed 
PFS) 
Sensitivity analyses of 
primruy endpoint 
Efficacy on secondary 
endpoints (investigator-
assessed PFS, OS, TTP, 
ORR, CBR, TTR, DOR) 
Patient Repo1ted 
Outcome 
Efficacy Subgroup 
Analyses 
Safety Analyses 
(AE, AEOSI, Death, 
Vital Sign, Clinical Lab, 
Screened 
Population 
X 
tent-to-Treat 
M-ve 
ITT) Population opulation 
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5. 
STATISTICAL METHODS AND ANALYSES 
5.1. 
Determination of Sample Size 
A hazard ratio (HR) of 0.667, likely corresponding to a 50% improvement in PFS, would be 
considered to be clinically meaningful in this relapsed/refractory locally advanced or metastatic 
TNBC patient population.  Four hundred and eighty-eight patients (488) patients are anticipated 
to be enrolled.  The population of patients with brain metastases will be capped at 15 % (N=74) 
of the trial population.  The primary PFS analysis will be performed when 425 investigator 
defined PFS events have occurred in all patients randomized as long as 315 or more PFS events 
have also occurred, according to Independent Review Committee (IRC) review, in the primary 
analysis population of patients without brain metastases (BM-ve population).  Assuming at most 
15% of patients have brain metastases and there are 13% or fewer IRC events compared to 
investigator review, it would be expected that there would be at least 315 IRC events in the BM-
ve population at the time 425 investigator PFS events have been observed amongst all patients 
randomized.  If the true HR is 0.667 in the IRC review of the BM-ve population, the study will 
have at least 95% power to detect a statistically significant improvement in PFS, with a two-
sided type 1 error rate of 5%, if data are analyzed after 315 IRC PFS.  PFS estimates in this 
patient population vary from 1.7 to 4.2 months (3 months average).  For an estimate of median 
PFS of 3 months in the control TPC group, and assuming a 24 month enrollment period, it is 
expected the primary PFS analysis will be performed after a minimum follow-up of 
approximately 4 months.    Overall survival will be analyzed at the time of the PFS analysis and 
also after 330 deaths have occurred in the primary analysis population of randomized patients 
without brain metastases.   The study will have approximately 89.5% power to detect an 
improvement in overall survival in the BM-ve population, with a two-sided 5% type 1 error rate, 
assuming that 72% of the planned number of deaths in BM-ve population have occurred at the 
time of the interim analysis (i.e., 238 deaths), and the true HR for OS is 0.7.   Assuming a 10 
month median in the control arm, a HR of 0.7 would likely correspond to a 4.3 month 
improvement.   The final analysis of OS is predicted to occur after a minimum follow-up of 17 
months, 13 months after the primary analysis of PFS. 
5.2. 
Interim analysis 
The originally planned interim analysis for futility based on progression free survival included in 
the Protocol (Amendment 1-4) is canceled and communicated to the FDA and thus excluded 
from this analysis plan.  
There will be an interim analysis of overall survival at the time of the final PFS analysis. A Lan-
DeMets spending function that approximates O’Brien-Fleming stopping boundaries will be 
applied to the interim OS analysis, where the 2-sided significance level applied is determined by 
(t) = 2-2Φ(-z/2/t).  In the equation, t is the number of OS events occurring at the interim 
divided by the number expected at the final analysis (i.e., 330) of the BM-ve population.  If the 
final number of events differs from expected, the final significance level will be adjusted so that 
the overall alpha is controlled given the significance level applied at the first analysis.   
 
 
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5.3. 
Overview of General Approaches 
Continuous data will be summarized using descriptive statistics: n, mean, median, standard 
deviation, minimum and maximum. Categorical data will be summarized using counts and 
percentages. For summary statistics, the tables will be presented by treatment arm, and 
additionally by an overall column unless otherwise specified. In general, a data listing will be 
provided for reference on endpoints to which summary or analyses are conducted. 
All statistical analyses will be performed using a two-sided hypothesis test at the overall 
5% level of significance. P-values will be rounded to three decimal places. The multiple 
comparisons procedure described in Section 5.11.1 will be used to control Type I error rate. 
Each category of analyses will be conducted in respective analysis populations according to 
Table 4 unless otherwise specified. 
Endpoints and analyses pertaining to the study’s primary and secondary objectives will be 
conducted as prescribed in respective sections of this SAP.  
 
 
 
 
 
  
5.4. 
Patient Accrual and Eligibility 
Number and percentage of subjects enrolled and randomized will be summarized and listed for 
the Screened Population by country and by site.  
Screen failures will be summarized for the Screened Population by the Inclusion/Exclusion 
criteria that were not met.  
A listing will be provided for each subject including informed consent date, randomization date, 
first dosing date, country and site for the Screened Population.  
5.5. 
Demographics  
Demographic characteristics will be summarized  using descriptive statistics, including but not 
limited to: age, age group, sex, race, ethnicity, height, weight, body mass index (BMI) and 
baseline creatinine clearance. 
A listing of demographic information will be provided for the ITT population. 
5.6. 
Baseline Disease Characteristics 
Summaries of baseline disease characteristics will include but not limited to the following 
variables: stratification factors employed in the randomization(number of prior treatments for 
metastatic or locally advanced disease, presence of known baseline brain metastases, and 
region), documented histology review of ER, PR and HER2 status as required by eligibility 
criteria, original diagnosis and time from diagnosis, UGT1A1 status, BRCA1 and BRCA 2 
mutational status, baseline ECOG score.  Prior treatment history including whether the patients 
have received prior breast-cancer related surgery and type of surgery, location and type of prior 
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radiotherapy will also be summarized. Presence of metastasis from baseline tumor scans will be 
categorized by location.  Patients’ hepatic function will be categorized by baseline serum 
bilirubin: (1) Normal (<= ULN) (2) >1-1.5 ULN (>1 and <=1.5 x ULN) and (3) >1.5 ULN (> 1.5 
x ULN). 
Medical history will be summarized by system organ class (SOC) and preferred term (PT) and 
sorted by frequency in SOC and by decreasing frequency in PT. 
Baseline disease characteristics and medical history listings will be provided for the ITT 
population.  
5.7. 
Patient Disposition 
The numbers and percentages of patients who are included in each analysis population will be 
summarized by treatment arm.  The number and percentages of patients who discontinue from 
the study and the reason for discontinuation will also be presented. The summary will also 
include the number of treatment cycles patients received.   The length of follow-up in each 
treatment arm will be summarized descriptively and the survival status during follow-up will be 
presented. 
A listing will be generated reflecting treatment group, date of randomization, date of first dose, 
date of last dose, date and reasons of treatment and study discontinuation, survival follow-up 
status and information  for each patient will be provided for the ITT Population. 
A listing of randomization scheme will be provided along with stratification factors after study 
unblinding at final analysis.  
5.8. 
Protocol Deviation 
Protocol deviations including violations of Inclusion and Exclusion Criteria will be summarized 
by importance and categories of deviation and listed for the ITT Population. 
5.9. 
Prior Anticancer Therapy, Prior and Concomitant Medications 
Prior anticancer systemic therapies (as entered on the Prior Systemic Therapy CRF), prior and 
concomitant medications (as entered on the Prior and Concomitant Medication CRF) will be 
coded using the World Health Organization (WHO) Drug Dictionary.  Prior medications include 
medication with a start and end date prior to first administration of study therapy.  Concomitant 
medications include medications that were taken at any time while on study treatment, including 
medication that were started before first administration of study therapy but ongoing at the time 
of first study therapy, or that were initiated on or after first administration but prior to 30 days 
after last administration of study therapy. If an end date is missing or the medication is ongoing 
during study treatment, the medication will be included as concomitant medication.  
Prior anticancer systemic therapies will be summarized according to WHO Drug Anatomical 
Therapeutic Chemical (ATC) Classification, and listed additionally with treatment setting, best 
response and reason for ending the treatment, start and end date, and date of progressive disease 
from the treatment.  
Prior medications and concomitant medications will be summarized according to WHO Drug 
Anatomical Therapeutic Chemical (ATC) Classification. 
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Prior anticancer therapy, prior and concomitant medications listings will be provided for the ITT 
Population.  
5.10. 
Exposure to Study Therapies 
Treatment exposure to study therapies will be summarized for treatment duration, number of 
doses received, and number of treatment cycles received.  Number and percentage of subjects 
who had a dose reduction and reasons for dose reduction,  number and percentage of subjects 
with 0, 1, 2, 3 and >3 dose reductions, time to the first dose reduction, number and percentage of 
subjects who had dose interruptions, or infusion terminated prematurely will be summarized for 
subjects who received IMMU-132, and for subjects on the TPC arm to the extent that  such drug 
exposure information were collected on CRF by each respective treatment of physician choice.   
Duration of treatment (in months) will be summarized and number of subjects with treatment 
duration longer than or equal to 6 months, 12 months, 24 months and 36 months will be 
summarized.   
For subjects who received IMMU-132, relative dose intensity will be calculated as described 
below  and summarized.  Cumulative dosage and relative dose intensity will be summarized by 
descriptive statistics, and relative dose intensity will be additionally summarized by the category 
of <50%, 50% to < 70%, 70% to <90%, 90% to <110%, >=110%. 
Delivered dose (in mg) for each infusion is calculated per CRF form from (“Dose calculated for 
this subject” x “Total volume administered”/“Total volume prior to administration”).  
Delivered dosage (in mg/kg) of each infusion in a cycle is calculated by dividing the delivered 
dose (in mg) by body weight (in kg) at the beginning of the cycle (the body weight according to 
which the prescribed dose is calculated and prepared per the Protocol).  
Cumulative dosage (in mg/kg) received for each subject is defined as the sum of all delivered 
doses (in mg/kg) of all infusions the subject received in the study. Total assigned dosage (in 
mg/kg) for each subject is defined as the product of the assigned dose of IMMU-132 (10 mg/kg) 
and number of doses the subject was scheduled to receive during the subject’s treatment period 
(number of infusions actually received by the subject plus the number of infusions the subject 
missed between the first and last infusion).  
Relative dose intensity (in %) for each subject is calculated: dividing the subject’s cumulative 
dosage received (in mg/kg) by the total assigned dosage (in mg/kg) as defined above.  
 
Treatment exposure will be summarized by the Safety Population and 
 and listed 
for the Safety Population.  
5.11. 
Efficacy Analysis 
5.11.1. 
Multiplicity Control 
The overall Type I error rate is strictly controlled at a two-sided alpha of 0.05, by a hierarchical 
testing strategy.  The primary endpoint of IRC assessed PFS will be analyzed and tested first in 
the ITT Population Without Brain Metastases (BM-ve Population), and if the primary analysis 
test is significant, subsequent key secondary endpoints (OS in BM-ve Population, IRC-assessed 
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PFS in the ITT Population, OS in the ITT Population) will be tested in a sequential manner as 
depicted in the diagram below, where a given hypothesis can only be declared statistically 
significant if all hypotheses above it in the hierarchy are also statistically significant. If fewer 
than 30 patients with brain metastases are recmited, analyses in the ITT population will be 
removed from the hierarchy. 
1111_ 
1111_ 
Overall survival will be analyzed both at the time of the primaiy PFS analysis (refened to as 
futerim OS analysis hereafter) and, if not statistically significant at this time, then later when a 
total of 330 deaths have occuned in the primaiy analysis population of randomized patients 
without brain metastases. A Lan-DeMets spending function that approximates 
O'Brien/Fleming stopping boundaries will be applied to the interim OS analysis, where the 2-
sided significance level applied is determined by a (t) = 2-2 <I> 
fu the equation, t is the 
number of OS events occmTing at the interim divided by the number expected at the final 
analysis (i.e., 330) of the BM-ve population. If the final number of events differs from expected, 
the final significance level will be adjusted so that the overall alpha is controlled given the 
significance level applied at the first analysis. 
The PFS ITT analysis will only be declai·ed as statistically significant if both the PFS BM-ve and 
OS BM-ve analyses have also been declai·ed as statistically significant. However, given the PFS 
ITT analysis will not be updated at the final OS analysis, a 2-sided significance level of 0.05 will 
be applied to this endpoint if and when both PFS and OS are statistically significant in the BM-
ve population. fu addition, OS in the ITT population will only be tested once PFS in the ITT 
population has been declared statistically significant. If this occurs at the time of the interim 
analysis, OS in the ITT population will be tested at the same adjusted alpha level computed for 
the analysis of OS in the BM-ve population. The significance level for the final analysis of OS in 
the ITT population will be detennined by the Lan-DeMets spending function to ensure alpha is 
controlled at a 2-sided alpha of 0.05 at the final OS analysis, if OS analyses in the ITT 
population is also conducted at the time of PFS analysis. The testing procedures and 
con esponding alpha levels for type I en or rate contrnl are depicted in the following diagram. 
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The primary outcome in this study is PFS; the secondary outcome is OS. The actual rates of 
occurrence of PFS events and deaths have been lower than the rates assumed in the study 
protocol. This reduction implies that the study will last much longer than anticipated if it 
continues until it reaches the targeted 315 PFS events in the primary BM-ve population. 
Therefore, on a recommendation from the DSMC and in consultation with the FDA, the Sponsor 
has elected to initiate the process of conducting the final primary analyses before the study 
reaches the protocol-specified 315 PFS events in the BM-ve population. In view that the 
recommendation was made prior to the 315 PFS events is reached, an adjustment will be 
imposed on the primary PFS analysis, according to the actual number of PFS events included in 
the database for this analysis, based on the Lan-DeMets alpha spending function that 
approximates O'Brien-Fleming stopping boundaries. If 302 of the 315 (or 96%) targeted PFS 
events are available, the 2-sided significant level to be applied will be 0.0443. Moreover, the 
number of deaths in the primary BM-ve population is close to reaching full maturity (316 of the 
330, or 96% of the deaths the protocol specified in the primary BM-ve population for the final 
OS analysis), thus this analysis will also serve as the final analysis for the secondary endpoint of 
OS.  
The original protocol and SAP specified two analyses of OS. The first was to occur at the time of 
the final PFS analysis when 72% of the planned number of deaths was expected. The second OS 
analysis was to occur when all 330 deaths had occurred in the BM-ve population.  Instead, only a 
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Yes 
PFS in ITT 
2-sided alpha = 0.05 
OS (interim) in ITT 
2-sided Lan-DeMets alpha 
Wait t ill OS data fully mature 
OS (fina l) in ITT 
2-sided Lan-DeMets alpha 
ad·usted at fina l 
PFS in BM-ve 
2-sided alp ha= 0.05 
OS (interi m} in BM-ve 
2-sided Lan-DeMets alpha 
ad'usted at interi m 
Testing procedure 
completed 
No 
Wait till OS data fully mature 
OS (fi na l) in BM-ve 
2-sided Lan-DeMets alpha 
adjusted at fina l 
PFS in ITT 
2-sided alpha = 0.05 
OS (fi nal ) in ITT 
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single, and therefore final, analysis of the study will occm . This analysis will serve as the final 
analysis for PFS, as described above, as well as the final analysis for OS for both the BM-ve and 
ITT populations. The 2-sided significance level for OS will be 0.0443(as illustrated above), as 
well as for the subsequent testing steps, inherited from the primaiy PFS test. This strntegy 
preserves that hierarchical testing strategy described in the SAP previously. Below is the 
updated diagram with the adjusted alpha level. 
5.11.2. 
Primary Analysis for Progression-Free Survival (PFS, primary endpoint) 
The primai·y analysis of PFS in the BM-ve Population for compai·ison between sacituzumab 
govitecan and the control TPC aim will be perfonned using a stratified log-rank test stratified by 
randomization factors as employed in the randomization. Estimate of hazai·d ratio and its 95% 
confidence interval will be based on stratified Cox proportional-hazards model with treatment 
aim as the only covai·iate, stratified by the same stratification factors employed in the 
randomization. The test comparing the treatment groups will be perfonned using a 2-sided alpha-
level of 0.05. PFS will be plotted over time using Kaplan-Meier (K-M) curves, median PFS and 
its associated 95% Cls are dete1mined by the Brookmeyer and Crowley method with log-log 
transfonnation. Milestone PFS rates at time points including 6 months, 9 months, and 12 months 
will be derived from KM estimates. 
5.11.3. 
Sensitivity Analysis of PFS 
Sensitivity analyses of PFS in the BM-ve Population and ITT Population will be generated 
following the FDA Guidance of Clinical Trial Endpoints for the Approval of Cancer Drngs and 
Biologics(December 2018) and Clinical Trial Endpoints for the Approval of Non-Small Cell 
Lung Cancer Drngs and Biologics (April 2015). The differences between the primaiy analysis 
PFS definition and compai·isons of their censoring rnles ai·e illustrated in Table 5. 
Sensitivity Analysis 1 
In the first sensitivity analyses of PFS (based on the central review), objectively documented 
progression or death will not be censored, regardless of the timing of the events. 
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Sensitivity Analysis 2 
A second sensitivity analysis (Sensitivity Analysis 2, corresponding to Table D1 in Appendix D 
of Clinical Trial Endpoints for the Approval of Non-Small Cell Lung Cancer Drugs and 
Biologics, April 2015) of PFS will be performed by assigning the dates for censoring and events 
only at scheduled assessment dates.  
Per the FDA guidance, this second type of sensitivity analysis may be biased if the progression 
occurred closer to the last assessment. 
Sensitivity Analysis 3 
A third sensitivity analysis (Sensitivity Analysis 3, corresponding to Table D2 in Appendix D of 
Clinical Trial Endpoints for the Approval of Non-Small Cell Lung Cancer Drugs and Biologics, 
April 2015) of PFS will be performed using a conservative approach by assigning the dates of 
discontinuation, change of treatment, or the 2nd missed scheduled assessment as an event date. 
Sensitivity Analysis 4 
A  fourth  sensitivity  analysis (Sensitivity Analysis4, corresponding to Table D3 in Appendix 
D of Clinical Trial Endpoints for the Approval of Non Small Cell Lung Cancer Drugs and 
Biologics, April 2015)  of  PFS  based  on  the  investigator's assessment. Clinical 
progression without documented radiographical progression will be considered as an event.   
Sensitivity Analysis 5 
The fifth sensitivity analyses will be done using the same primary definition of PFS but will be 
conducted in the corresponding Safety Population subjects who received study therapies, instead 
of the ITT and BM-ve Population.  
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Table 5: 
Sensitivity Analyses of PFS and Corresponding Censoring Rules 
Case 
Primaiy 
Sensitivity 
Sensitivity 
Sensitivity 
Sensitivity 
Sensitivity 
Analysis PFS 
Analysis 1 
ki\nalysis 2 
ki\nal ysis 3 
ki\nalysis 4 
Analysis 5 
definition 
(Based on 
!investigator 
~ssessed PFS) 
No adequate response assessment after 
Use the 
randomization 
same 
Died prior to 
Date of Death 
Date of Death !Date of Death !Date of Death !Date of Death 
.... ensoring 
uleof 
second 
Primaiy 
scheduled 
Analysis 
assessment 
PFS 
Did not die or 
Censored at 
Progressed at Censored at 
Censored at 
K:ensored at 
definition 
died after 
Randomization 
date of Death 
!Randomization i·andomization IR.andomizatioll but in 
missing 2 or 
if died; or 
~f did not die, 
Safety 
more 
censored at 
progressed on 
Population. 
scheduled 
date of 
~he date of 2nd 
For 
assessments 
randomization 
1nissed 
sensitivity 
if did not die 
!scheduled 
analysis of 
assessment 
PFS 
Continued scheduled response assessments 
analysis in 
until objective PD or death 
the ITT 
opulation, 
PD at 
Date of PD 
Date of PD 
IDate of PD if at IDate of PD 
IDate of PD if use Safety 
scheduled 
$cheduled 
~t scheduled 
Population 
assessment, or 
~ssessment; 
~ssessment; 
instead; for 
prior to 
!Date of next 
!Date of next 
sensitivity 
inissing 2 
!scheduled 
scheduled 
analysis of 
scheduled 
assessment if 
~ssessment if PFS in the 
successive 
IPD between 
IPD betv.•een 
BM-ve 
assessments 
$cheduled 
scheduled 
Population, 
~ssessments or 
~ssessments or use Safety 
1>rior to inissing 
prior to 
Population 
scheduled 
!missing 2 
without 
$uccessive 
scheduled 
Baseline 
~ssessments. 
successive 
Brain 
including PD 
~ssessments. 
Metastasis 
•hat occwTed at 
instead. 
!End of 
tt'reatment/Eady 
KVithdrawal 
K,-isits) 
Clinical PD 
NIA 
NIA 
NIA 
NIA 
!Date of next 
indicated 
scheduled 
between 
~ssessment 
scheduled 
assessments or 
prior to 
inissing 2 
scheduled 
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successive 
assessments 
Death betv.•een 
Date of Death 
Date of death 
IDate of death 
IDate of Death IDate of death 
scheduled 
assessments, or 
prior to 
missing 2 
scheduled 
successive 
assessments 
PD or death 
Censored at 
Date of PD or Censored at 
!Progressed at t:ensored at 
after missing 2 
Date oflast 
Death 
IDate of last 
~ nd missed 
IDate of last 
or more 
adequate 
adequate 
ischeduled 
~dequate 
scheduled 
response 
·esponse 
~ssessment 
~-esponse 
assessments 
assessment 
assessment 
~ssessment 
before missed 
~efore missed 
~efore missed 
assessments 
assessments 
~ssessments 
Treatment 
Included in 
Included in 
i[ncluded in 
!Progressed at i[ncluded in 
discontinuation other scenario 
other scenario K>ther scenario llie time of 
K>ther scenario 
for 
kliscontinuatior 
undocumented 
progression, 
toxicity or 
other reason 
Continued scheduled response assessments 
without objective PD 01· death 
Initiated other 
Censored at 
Date of 
Censored at 
!Progressed on K:ensored at 
anti-cancer 
Date of last 
documented 
!Date of last 
llie date of 
!Date of last 
treatment 
adequate 
progression or ~dequate 
lstait of anti-
~dequate 
response 
death if 
esponse 
K;ancer 
1t·esponse 
assessment 
occun-ed 
~ssessment 
~eatment 
~ssessment 
with 
with 
~•ith 
documented 
klocumented 
klocumented 
non-
non-progression 
non-
progression 
prior to staiting 
tprogression 
prior to 
K>ther anti-
tprior to 
staiting other 
~ancer 
staiting other 
anti-cancer 
lreatment 
~nti-cancer 
treatment 
~reatment 
No objective 
Censored at 
Censored at 
Censored at 
K:ensored at 
K:ensored at 
PD or death 
Date of last 
Date oflast 
!Date of last 
!Date of last 
!Date of last 
adequate 
adequate 
~dequate 
~dequate 
~dequate 
response 
response 
esponse 
1t·esponse 
1t·esponse 
assessment 
assessment 
~ssessment 
~ssessment 
~ssessment 
1 
Adequate response assessment was defined as a response assessment other than 'not assessed' or 'not 
evaluable'. If progression was based on the sum of target lesion measurements at different time points, the last 
measurement date was to be used as the date of progression. For progression based on new or non-target 
lesions considered unequivocal progression, the earliest date when progression was detected was to be used as 
the date of progression. 
The endpoint of PFS will be indicated censored if explicitly stated as censored and calculated at the specified 
time description ; othenvise PFS will be indicated as an event at the specified time description. 
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5.11.4. 
Overall Survival 
OS will be analyzed by the same method as the primary PFS analysis.   
Milestone OS rates at time points including 12 months, 18 months and 24 months will be derived 
from the KM estimates.   
5.11.5. 
Time to Progression  
The Time to Progression will be analyzed by the same method as the primary PFS analysis.  
5.11.6. 
Objective Response Rate and Clinical Benefit Rate 
The objective response rate (ORR) and Clinical Benefit Rate (CBR) will be summarized based 
on both IRC assessment and investigator assessments, along with number and percentage of 
subjects with a best overall response of complete response (CR), Partial response (PR), Stable 
Disease (SD), SD with a duration of 6 months or longer, Progressive Disease (PD), and Not 
Evaluable (NE).  For subjects who were assessed as without measurable disease at baseline by 
IRC, the additional category of Non-CR/Non-PD will be added.  ORR and CBR will be analyzed 
and compared between the treatment arms using the Cochran-Mantel-Haenszel method stratified 
by the stratification factors used in the randomization. The 2-sided 95% CIs will be calculated by 
the Clopper-Pearson exact method.  
A sensitivity analysis of ORR and CBR will be conducted in an “Efficacy Analyzable 
Population”, defined as randomized and treated patients who received at least one cycle of 
IMMU-132 or TPC and at least two post-baseline radiological assessment data. 
5.11.7. 
Time to Response (TTR) and Duration of Response (DOR) 
Only patients achieving CR or PR will be included in the calculation for Time to Response and 
Duration of Response (DOR) analyses. TTR will be summarized by descriptive statistics, and by 
the number of percentage of responders whose TTR is within 3 months, 6 months and 12 
months.  DOR in each treatment arm will be estimated using the Kaplan-Meier method, and 
analyzed by the same method as the primary PFS analysis. The number and percentage of 
responders with a DOR greater than or equal to a timeline including 3 months, 6 months, 9 
months and 12 months will be estimated. 
5.11.8. 
Patient Reported Outcome 
Descriptive statistics and summaries of the EORTC-QLQC30 physical functioning subscale will 
be presented by treatment group. As EORTC QLQ C30 are completed by patients on Day 1 of 
each cycle, and at final study visit. If patients did not receive dosing, they will lack this 
measurement on Day 1 of each treatment cycle, therefore, this analysis will be conducted in the 
Safety Population only.  
5.11.9. 
Other Analyses and Listings 
For the primary endpoint of PFS in the ITT Population and BM-ve Population, a summary table 
will be provided for the number and frequency of events vs. subjects whose PFS is censored.  
For events, PFS will be further summarized by the type of events of whether it is Progression or 
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death, and for censored subjects, according to the reason of censoring according to the censoring 
rule Table 1. 
A summary of baseline tumor assessment will be provided for target lesions and non-target 
lesions and target lesion/non-target lesion combined according to anatomical location for the ITT 
population and BM-ve Population.   
For the ITT Population, the following listings will be provided for IRC assessed and investigator 
assessed tumor response, respectively: 1) a listing of all tumor assessments including tumor 
assessment results (target, non-target and new lesions) 2) a listing of tumor response at each 
assessment time point and best overall response for the subject, 3) a listing for all responders 
(CR and PR) with their best overall response, time to response and duration of response; 4) a 
listing of   the magnitude of tumor burden reduction in target lesions. 
A plot of target-lesion tumor burden (spider plot) will be provided and a plot of maximum tumor 
burden reduction (waterfall plot) will be provided for the ITT population and BM-ve Population, 
for IRC-assessed and investigator assessed results.  
Concordance between IRC assessed and investigator assessed tumor response will be 
summarized by a contingency table of responders (CR+PR), non-responders (SD + PD for 
investigator-assessed, SD + PD + non-CR/non-PD for IRC-assessed) and NE, for ITT Population 
and BM-ve Population.  
For the ITT Population, a listing will be provided for subsequent anti-cancer therapies including 
drug name, start and stop date (and study day relative to date of randomization), progression date 
if radiographically progressed, end-of-treatment date and reason (including clinical or 
radiographical progression if progressive disease is listed as reason), and death date if known.  
For the ITT Population, a listing of PFS and OS will be provided including PFS time and OS 
time, radiographical progression date if the subject had a radiographical progression, death date 
if known, censoring information for PFS and OS, and reasons for censoring of PFS and OS, 
respectively.   
The outbreak of the COVID-19 pandemic in early 2020 has affected the clinical operations of the 
trial and consequently the collection of clinical data.  Some protocol-specified data points may 
not be collected on schedule or even at all for subjects who still remain on treatment or for those 
who have stopped treatment but are still being followed.  Some sensitivity analyses will be 
performed excluding data collected that are impacted by COVID-19 to explore the extent to 
which COVID-19 may have affected inference from the study. 
 
5.11.10. 
Subgroup Analyses 
Subgroup analyses including but not limited to the following demographic, disease 
characteristics and prognostic factors will be applied to the ITT Population and BM-ve 
Population, for the primary endpoint of PFS, secondary endpoints of OS and ORR. A Forest plot 
of treatment effect on these endpoints in the subgroups will be generated.  
 Age group (<65 vs >=65) 
 Race (White, Black, Asian, Other);  
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 Prior therapies: (2, 3, 2-3, and >3);  
 Brain metastases (Yes, No; ITT only);  
 Region (North America, Rest of World);  
 Original diagnosis TNBC (Yes, No);  
 UGT1A1 status  
 BRCA 1 status (Positive, Negative)  
 BRCA 2 status (Positive, Negative) 
 Trop-2 Status 
 Presence of liver metastasis at baseline (Yes, No) 
 
 
 
 
 
  
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
5.12. 
Safety Analyses 
Safety analyses will be conducted in the Safety Population. 
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5.12.1. 
Adverse Events 
Treatment-emergent adverse events (TEAEs) are defined as any AEs that begin or worsen on or 
after the start of study drug through 30 days after the last dose of study drug. All AEs will be 
coded using Medical Dictionary for Regulatory Activities (MedDRA). The severity will be 
graded based on the National Cancer Institute’s (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE). Only TEAEs will be summarized and will be referred to as AEs 
hereafter. 
The frequency and severity of AEs, classified by MedDRA, will be summarized by treatment 
group and overall using MedDRA Preferred Term and System Organ Class (SOC).  An AE that 
occurs more than once within each patient will be counted only once in the summaries, i.e., 
where a subject has the same adverse event, based on preferred terminology, reported multiple 
times, the subject will only be counted once at the preferred terminology level in adverse event 
summary tables. Where a subject has multiple adverse events within the same system organ 
class, the subject will only be counted once at the system organ class level in adverse event 
summary tables. When reporting adverse events by CTC grade, summary tables will be provided 
using the worst NCI-CTCAE grade.  
The following AE summary tables and listings will be provided: 
 Overall Summary of Treatment-Emergent Adverse Events 
 Summary of Treatment-Emergent Adverse Events by SOC and PT 
 Summary of NCI-CTCAE Grade 3 or Higher Treatment-Emergent Adverse Events 
by SOC and PT 
 Summary of Treatment-related Treatment-Emergent Adverse Events by SOC and 
PT  
 Summary of NCI-CTCAE Grade 3 or Higher Treatment-related Treatment-
Emergent Adverse Events by SOC and PT 
 Summary of Treatment-Emergent Adverse Events by Worst CTCAE Grade, SOC 
and PT  
 Summary of Treatment-related Treatment-Emergent Adverse Events by Worst 
CTCAE Grade, SOC and PT 
 Summary of Treatment-Emergent Serious Adverse Events by SOC and PT  
 Summary of Treatment-related Treatment-Emergent Serious Adverse Events by 
SOC and PT  
 Summary of Treatment-Emergent Adverse Events by SOC and PT in Patients by 
UGT1A1 Result  
 
 
  
 Summary of Treatment-Emergent Serious Adverse Events by SOC and PT in 
Patients by UGT1A1 Results 
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 Summary of Treatment-Emergent Adverse Events Leading to Dose Reduction by 
SOC and PT  
 Summary of Treatment-Emergent Adverse Events Leading to Study Drug 
Interruption by SOC and PT  
 Summary of Treatment-Emergent Adverse Events Leading to Study Drug 
Discontinuation by SOC and PT 
 Summary of Treatment-Emergent Adverse Events Reported by >=10% Patients in 
Any Treatment Arm by Preferred Term  
 Summary of NCI-CTCAE Grade 3 or Higher Treatment-Emergent Adverse Events 
Reported by >=5% Patients in Any Treatment Arm by Preferred Term  
 Summary of Treatment-Emergent Serious Adverse Events Reported by >=2% 
Patients in Any Treatment Arm by Preferred Term  
 Summary of Treatment-Emergent Serious Adverse Events Leading to Death by 
SOC and PT  
The following AE listings will be provided: 
 Listing of All Adverse Events.  
 Listing of Serious Treatment-Emergent Adverse Events 
 Listing of Treatment-Emergent Adverse Events Leading to Death 
 Listing of Treatment-Emergent Adverse Events Leading to Dose Reduction 
 Listing of Treatment-Emergent Adverse Events Leading to Study Drug Interruption  
 Listing of Treatment-Emergent Adverse Events Leading to Study Drug 
Discontinuation 
All TEAEs by SOC/PT and the overall TEAE summary table for the following subgroups will be 
provided: 
 Age group (<65 vs >=65) 
 Race (White, Black, Asian, Other) 
 Ethnicity 
 Brain metastases (Yes, No) 
 
  
 Patients’ hepatic function by baseline serum bilirubin: (1) Normal (<= ULN) (2) >1-
1.5 ULN (>1 and <=1.5 x ULN) and (3) >1.5 ULN (> 1.5 x ULN). 
In addition, treatment-related TEAEs and Serious TEAEs will be provided by subgroups 
according to 
 and hepatic functioning. 
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5.12.2. 
Adverse Events of Special Interest (AEOSI) 
In addition to analyses of AEs, adverse events of special interest (AEOSI) will be assessed. 
Definitions of AEOSI, as currently defined, are provided in Table 6, including but not limited to 
listed. For AEOSI, frequency tables will be generated, showing overall summary of AEOSI, 
Summary of AEOSI by SOC and PT, Serious AEOSI by SOC and PT, AEOSI leading to 
discontinuation by SOC and PT, AEOSI leading to treatment interruption by SOC and PT, Grade 
3 or higher AEOSI by SOC and PT, treatment-related AEOSI (by a worst CTCAE grade of 3, 4, 
or 5, >=3 and any grade) by SOC and PT. Corresponding listings will also be produced. 
Table 6: 
Definitions of Adverse Events of Special Interest 
Adverse Event of Special 
Interest 
Definition 
Diarrhea 
Preferred term: diarrhea 
Nausea 
Preferred term: nausea 
Vomiting 
Preferred term: vomiting 
Neutropenia+ 
Preferred terms: neutropenia, neutrophil count decreased, febrile 
neutropenia 
Febrile neutropenia+ 
Preferred term: febrile neutropenia 
Infections 
SOC: infections and infestations 
Anemia+ 
Preferred terms: anemia; hemoglobin decreased  
Thrombocytopenia+ 
Preferred terms: thrombocytopenia; platelet count decreased 
Fatigue 
Preferred term: fatigue and asthenia 
Neuropathy+ 
Preferred term: gait disturbance, hypoesthesia, muscular weakness, 
neuropathy peripheral, paresthesia, and peripheral sensory neuropathy 
Abbreviation: SMQ=Standard MedDRA Query 
All definitions based on MedDRA vs 20.0 
+ Grouped AE terms 
 
5.12.3. 
Death 
All-cause deaths will be summarized (including presentation of causes of death), and deaths 
within 30 days of the last dose of study drug will be summarized.  A listing of all death 
information will be generated. 
5.12.4. 
Vital Sign 
Both actual and change-from-baseline data on vital signs (heart rate, systolic and diastolic blood 
pressure, respiratory rate, and body temperature) will be summarized using descriptive statistics 
by treatment group for each study time-point.  
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5.12.5. 
Electrocardiograms 
Descriptive statistics for the actual values and changes from baseline over time will be 
summarized for the ECG parameters including Ventricular Rate, QT, PR, QRS, QTcB and QTcF 
corrections. 
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The proportion of patients with maximum post-baseline absolute QTcF/QTcB intervals who fall 
into the following categories will be presented: 
 ≤ 450 msec 
 > 450 msec 
 > 450 to ≤ 480 msec 
 > 480 to ≤ 500 msec 
 > 480 msec 
 > 500 msec 
The proportion of patients who have a maximum post-baseline increase from baseline in 
QTcF/QTcB intervals of the following categories will be presented: 
 ≤30 msec 
 > 30 msec 
 >30 to ≤60 msec 
 >60 msec 
The shift table of overall interpretation (‘Normal,’ ‘Abnormal, not clinically significant,’ and 
‘Abnormal, clinically significant’) from baseline to post-baseline evaluation will also be 
provided by treatment and by overall. 
5.12.6. 
Clinical Laboratory Evaluations 
Routine safety laboratories, based on hematology and routine serum chemistry data (including 
but not limited to glucose, creatinine, BUN, total bilirubin, AST, ALT, LDH, alkaline 
phosphatase, serum albumin, total protein, Na, K, calcium, Cl, CO2, magnesium and phosphate), 
will be summarized using values at each visit and change from baseline using descriptive 
statistics for each treatment group and overall.  Laboratory test results for lab parameter 
including but not limited to platelets, neutrophils, white blood count, lymphocytes and 
hemoglobin will be graded according to NCI-CTCAE severity grade.  A shift table of the worst 
NCI-CTCAE grade observed on-treatment will be tabulated for each lab parameter and presented 
in a frequency table by baseline grade.  For parameters for which a CTCAE scale does not exist, 
the proportion of patients with abnormal values will be summarized by dose group. 
5.12.7. 
Physical Exam and Pregnancy Test 
Physical exam results are listed according to body system and presented for any abnormal 
findings from the physical examination. 
Pregnancy test results will be listed.  
 
  
 
 
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5.15. 
Data Handling Rules 
Data and programming specification and rules, including but not limited to the following, are 
described below. 
5.15.1. 
Conversions from Days to Years, Months or Weeks 
Years = # of days / 365.25 (use of SAS function) Months = # of days / 30.4375 (i.e. 365.25/12) 
Weeks = # of days / 7 
Values based on the above computations will be rounded to tenths. 
Age will be calculated using the following formula in SAS, where birthdate is the SAS date 
corresponding to birth date and icdate is the date of informed consent: 
Age=intck(‘YEAR’, birthdate, icdate (_),’C’); 
5.15.2. 
Computation of Duration 
Duration for time variables based on two dates, e.g., Start Date and End Date, will be calculated 
as (End Date – Start Date + 1) (in days) unless otherwise specified. 
5.15.3. 
Missing normal ranges for laboratory parameters 
When either the lower limit of normal, the upper limit of normal or both are missing or are not 
machine readable, a standardized reference range will be used. 
5.15.4. 
Non-Numeric Laboratory Results and Calculation of Normal Ranges 
Laboratory values including symbols (“<” or “>”, for example) will not be used in summary 
analyses.   These values will be reflected in listings of the data. When there are potential conflicts 
between local lab normal ranges and ranges used in CTC grading, CTC normal ranges will be 
used. 
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5.15.5. 
Imputation of Missing or Incomplete Dates 
Missing Data Imputation for Adverse Event/Concomitant Medication Start Dates  
1. Missing day only  
 If the month and year of the AE/the concomitant medication are the same as the 
month and year of the first IMMU-132 dose date, the first dose date day will be used.  
 If the month and year are before the month and year of the first dose date, the first 
day of the month will be assigned to the missing day.  
 If the month and year are after the month and year of the first dose date, the first day 
of the month will be assigned to the missing day.  
2. Missing day and month  
 If the year is the same as the year of the first dose date, the first dose date day and 
month will be used.  
 If the year is prior to the year of the first dose date, December 31 will be assigned to 
the missing fields.  
 If the year is after the year of the first dose date, January 1 will be assigned to the 
missing fields.  
3. Missing day, month, and year  
 The first dose date will be used.  
The imputed start date should be prior or equal to the end date of the AE or medication.  
Missing Data Imputation for Missing Adverse Event/Concomitant Medication Stop Date  
1. Missing day only  
 The month and year are the same as the month and year of the first dose date: use the 
last date of the month. 
 The month and year are before the month and year of the first dose date: use the last 
date of the month. 
 The month and year are after the month and year of the first dose date: use the last 
date of the month.  
2. Missing day and month  
 The year is the same as the year of the first dose date: use December 31.  
3. Missing year  
Uncertain: unable to impute.  
4. Missing month  
 • The year is the same as the year of the first dose date: use December.  
 • The year is before the year of the first dose date: use December. 
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 • The year is after the year of the first dose date: use December.  
5. Missing month and year  
Uncertain: unable to impute  
6. Missing day and year  
Uncertain: unable to impute  
7. Missing day, month, year  
This event is ongoing. 
If the death date is available and the imputed end date is after the death date, the death date will 
be used.  
If the imputed end date is after the start date of the AE or medication, then make end date equals 
to start date. 
5.16. 
Statistical Software used in data analysis 
All statistical analyses will be performed using SAS® (SAS Institute, 2010) Version 9.2 or later 
 
 
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6. 
REFERENCES 
Cox, D.R. (1972).  Regression models and life tables (with discussion).  Journal of the Royal 
Statistical Society, B34:187-220. 
E.A. Eisenhauer, et,al. New response evaluation criteria in solid tumours: Revised RECIST 
guideline (version 1.1). EJC 45(2009) 228 – 247. 
Hosmer, D.W., and Lemeshow, S. (2000).  Applied logistic regression, second edition.Hoboken: 
John Wiley & Sons, Inc. 
Kaplan, E.L., and Meier P. (1958). Nonparametric estimation from incomplete observations.  J 
Am Stat Assoc, 53:457-481. 
Klein JP, Logan B, Harhoff M, Andersen PK. (2007). Analyzing survival curves at a fixed point 
in time. Stat Med. 2007 Oct 30; 26(24):4505-19. 
Mantel, N. (1966).  Evaluation of survival data and two new rank order statistics arising in its 
consideration.  Cancer Chemotherapy Reports, 50:163-170. 
Mantel, N., and Haenszel, W. (1959).  Statistical aspects of the analysis of data from 
retrospective studies of disease. J National Cancer Inst., 22:719-748. 
Pocock, S., and Simon, R. (1975). Sequential treatment assignments with balancing for 
prognostic factors in the controlled clinical trial. Biometrics 31: 103-115. 
SAS Institute Inc. (2010).  SAS/STAT® 9.2 User’s guide.  Cary, NC: SAS Institute Inc. 
US Dept. Health and Human Services, FDA (Jan.2017)  Multiple Endpoints in Clinical Trials, 
Guidance for the Industry 
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Prot_000.pdf: 
Immunomedics, Inc. 
IMMU-132-05 
 
Sacituzumab Govitecan 
 
26 August 2019 
CONFIDENTIAL 
Page 1 
 
 
  IMMUNOMEDICS®, INC. 
 
 
PROTOCOL: IMMU132-05 
 
Phase III Study of Sacituzumab Govitecan 
(Immu-132) 
In Relapsed/Refractory 
Triple-Negative Breats Cancer 
 
 
Protocol Title: 
An International, Multi-Center, Open-Label, Randomized, Phase 
III Trial of Sacituzumab Govitecan versus Treatment of 
Physician Choice in Patients with Metastatic Triple-Negative 
Breast Cancer Who Received at Least Two Prior Treatments 
 
IND #: 
122694 
 
EudraCT Number:   2017-003019-21 
 
Sponsor: 
Immunomedics, Inc. 
300 The American Road 
Morris Plains, NJ  07950 
Telephone: 
 
Facsimile: 
 
  
Release Date: 
November 18, 2015 
 
Revision Date: 
August 26 2019 (Includes Amendments 1- 6) 
 
 
 
 
This protocol contains information that is confidential and proprietary to 
Immunomedics, Inc. 
All rights reserved. No part of this protocol may be copied, reproduced, referenced, 
stored in a retrieval system or transmitted, in any form or by any means, electronic, 
mechanical, photocopying, recording, or otherwise, without prior written permission 
of Immunomedics, Inc. 
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Protocol Sections 
Protocol 
IN THE EVENT 
OF EMERGENCY 
Synopsis 
Scope of Study 
26 August 2019 
SUMMARY OF CHANGES 
Change 
Minor typographical, grammatical and 
fo1matting co1Tections were made throughout 
the protocol. 
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fa.~r Ii-Bes will Go fi~e:i.z:iQeQ te sites 
Old Text: Four hundred and eighty-eight 
patients ( 488) are anticipated to be enrolled. 
Up to approximately 150 institutions will 
paii icipate in this study, including sites in 
North America, Europe aml 13ete~iaUy 
elsev/Bore. 
New Text: Approximately four hundred and 
eighty-eight patients ( 488) are anticipated to 
be enrolled. Up to approximately 150 
institutions will paiiicipate in this studYi 
including sites in North America, and Euro12e. 
CONFIDENTIAL 
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Rationale 
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consistency 
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Synopsis Study 
Design 
Synopsis 
Study Procedure 
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Sample Size 
Old Text: Four hundred and eighty-eight 
patients (488) patients are anticipated to be 
enrolled.  The population of patients with 
brain metastases will be capped at 15 % 
(N=74) of the trial population.  The primary 
PFS analysis will be performed when 425 
investigator defined PFS events have occurred 
in all patients randomized as long as 315 or 
more PFS events have also occurred, 
according to Independent Review Committee 
(IRC) review, in the primary analysis 
population of patients without brain 
metastases (BM-ve population). 
New Text Approximately four hundred and 
eighty-eight patients (488) patients are 
anticipated to be enrolled.  The population of 
Updated for clarification 
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patients with brain metastases will be capped 
at 15 % (N=74) of the trial population.  The 
primary PFS analysis will be performed when 
425 investigator defined PFS events have 
occurred in all patients randomized as long as 
315 or more PFS events have also occurred, 
according IRC review, as defined for the 
primary analysis in the primary analysis 
population of patients without brain 
metastases (BM-ve population).   
Centralized 
Procedures 
Deleted Text:  The DSMC reviews will 
include one planned interim futility analysis of 
data on progression-free survival (based on the 
central assessment) at 50% (approximately 
213events) of the required 425 progressions or 
deaths for final analysis. For this interim 
futility analysis, the DSMC will be guided by 
the pre-specified futility monitoring 
boundaries based on a fixed boundary of 
HR=0.999 applied to the brain metastasis 
negative population. The DSMC will consider 
all available safety and efficacy data prior to 
formulating its recommendations regarding 
continuation or termination of the trial. If 
futility is not demonstrated for the primary 
endpoint of PFS, the trial will continue. 
New Text: The DSMC will consider all 
available safety and efficacy data prior to 
formulating its recommendations regarding 
continuation or termination of the trial. 
Interim analysis for 
futility was not 
performed due to rapid 
enrollment 
Data Analysis  
Old Text: 
 
 
 
 
 
 
 
 
 
 
 
 
  
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New Text: 
 
 
 
 
 
 
 
 
 
 
 
 
 
LIST OF 
ABBREVIATIONS 
Added Text:  IMMU-132 Company Code for 
sacituzumab govitecan 
For consistency  
3.1 Study Overview 
 
Old Text: Four-hundred eighty-eight (488) 
patients from up to 150 centers, including sites 
in North America, Europe and potentially 
elsewhere will be randomized 1:1 to the 
following treatment arms: 
New Text: Approximately four hundred 
eighty-eight (488) patients from up to 
approximately 150 centers, including sites in 
North America, and Europe will be 
randomized 1:1 to the following treatment 
arms: 
For consistency with 
synopsis  
3.2 Data Safety 
Monitoring 
Committee 
(DSMC) 
Old Text: An independent DSMC will be 
convened at regular intervals to assess the 
progress of this study, and review safety and 
progression data, per an adopted DSMC 
charter.  In the absence of unexpected safety 
concerns, or futility at the time of interim 
analysis for meeting the primary PFS 
endpoint, the study will continue. 
New Text: An independent DSMC will be 
convened at regular intervals to assess the 
progress of this study, and review safety and 
progression data, per an adopted DSMC 
charter.  In the absence of unexpected safety 
concerns,  the study will continue. 
Interim analysis for 
futility was not 
performed due to rapid 
enrollment  
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5 
STUDY 
PROCEDURES 
 
 
 
   
 
 
 
 
   
 
  
5.3 
Pre-
Study/Baseline 
Evaluations 
 
 
 
 
 
 
 
 
 
 
 
   
  
5.4  
Procedures 
During Treatment 
Old Text: Anti-drug antibody sample 
(hRS7,SN38frozen immediately, to be shipped 
to Sponsor’s designee for analysis) [For 
IMMU-132, required Day 1 of even cycles. 
For TPC, not applicable] 
New Text: Anti-drug antibody sample (frozen 
immediately, to be shipped to Sponsor’s 
designee for analysis) [For IMMU-132, 
required Day 1 of even cycles. For TPC, not 
applicable] 
Clarification 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
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5.9 End of Study  
Deleted Text: As at the end of study, in the 
event the Investigator believes a patient is 
continuing to receive clinical benefit, the 
Sponsor will discuss options with the 
Investigator in order to ensure the potential for 
continuing supply of sacituzumab govitecan. 
 
Added Text: At the completion of the trial, 
subjects who are deriving benefit from 
sacituzumab govitecan may continue to 
receive treatment in a rollover study, if one is 
available. This rollover study may be designed 
to provide continued access to sacituzumab 
govitecan for eligible subjects who have 
previously participated in Immunomedics 
sponsored parent study, who are tolerating 
sacituzumab govitecan, have no evidence of 
progressive disease or are still deriving 
clinical benefit despite progression (as 
assessed by the investigator). Subjects will 
receive the dose ofsacituzumab govitecan 
currently receiving in the parent study at the 
time of consenting to participate in the 
rollover study, if applicable. 
 
6.3 Study Drug 
Preparation 
 
Added Text: Please use Pharmacy Binder 
as primary source for study drug 
preparation.  
Deleted Text: For patient dose preparation, 
IMMU 132 is to be reconstituted with normal 
saline for use within 8 hours after 
preparation.  Appropriate use of aseptic 
technique should be employed in preparing the 
dose.  Allow the IMMU 132 vials to warm to 
room temperature to allow faster dissolution.  
The 200 mg of lyophilized powder in each vial 
should be reconstituted using 20 mL of 0.9% 
sterile sodium chloride (normal saline). The 
reconstituted solution should be gently shaken 
and allowed to dissolve for up to 15 minutes. 
Calculate the prescribed dose in mg based on 
the patient’s body weight at the beginning of 
EACH cycle (or more frequently for > 10% 
Clarification and to be 
consistent with Pharmacy 
manual   
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change in body weight or if required by 
institutional policy).  The appropriate 
calculated amount should then be withdrawn 
from the supplied vials of study medication.  
Inject the solution into a glass or plastic 
infusion container slowly to minimize 
foaming and do not shake the contents. Adjust 
the volume in the infusion container as needed 
with normal saline to obtain a concentration of 
1.1 3.4 mg/mL (total volume should not 
exceed 500 mL).  Only normal sterile saline 
should be used since the stability of the 
reconstituted product has not been determined 
with other infusion  based solutions.  A 
sample drug preparation chart for a 70 kg 
patient is provided in Table 3 with 200 
mg/vials and 250 mL bags of normal saline as 
the infusion container. The prepared study 
drug is stable for up to 8 hours at room 
temperature 
Table 6 
Deleted Text : (refer to table 9 A)  and ( refer 
to table 9B) 
No table 9A or 9B  
7 STUDY 
EVALUATIONS  
 
 
 
   
 
 
   
 
 
 
   
 
 
 
   
 
  
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8.2 Reporting 
AE’s/SAE’s  
Old Text: Disease progression is a worsening 
of a patient’s condition attributable to the 
disease for which the study medication is 
being given. This may be an increase in 
severity of the disease or an increase in the 
symptoms of the disease. New or increasing 
symptoms related to disease progression 
should be reported as an AE; unless death 
occurs within  30 days of the patient’s last 
dose of study medication. 
Added Text:. In this protocol, disease 
progression is an efficacy endpoint and should 
not be reported as an AE. It is important to 
differentiate expected disease progression 
from an AE. Events that are clearly consistent 
with the expected pattern of disease 
progression should not be considered AEs. 
Expected disease progression refers to an 
event that is unequivocally related to disease 
progression, and that the clinical course is 
consistent with what would be expected for 
the patient’s disease. A clinical event in the 
setting of disease progression would be 
considered an AE if it could not be 
unequivocally attributed to or consistent with 
expected disease progression.  
Clarification of text 
8.2 Reporting 
AEs/SAEs 
Deleted Text: For SAEs, the Sponsor  
designated contact is to be notified by the 
Investigator, using the designated form, 
within 24 hours of the site becoming aware 
of the event.  The initial report is to be 
followed by submission of more detailed SAE 
information within 5 calendar days of the 
event. 
Added Text: All SAEs and pregnancies must 
be reported to the Sponsor or the Sponsor’s 
designee immediately, and no later than 24 
hours of becoming aware of the event. 
All SAEs and pregnancies should be reported 
to the Sponsor’s designee as per the reporting 
instructions provided on the SAE Form 
Completion Guidelines and as stated on the 
SAE Form.  
Update to safety 
language to be consistent 
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8.2 Reporting 
AEs/SAEs 
Deleted Text:  
Synteract 
 
 
 
Telephone*: 
 
Facsimile*: 
 
E mail: 
 
 
 
*additional toll free country 
specific phone or fax lines will be 
provided to sites 
 
 
Removal of Synteract 
information 
8.7 Expedited 
Reporting 
Old Text: In this trial, Synteract is responsible 
for expedited reporting of any SAE considered 
to be SUSAR (Suspected Unexpected Serious 
Adverse Reaction). 
A SUSAR is any adverse event which meets 
the following 3 criteria  
 
Serious Adverse Event.  An event 
meeting the SAE criteria in Section 
8.1. 
 
Suspected 
Adverse 
Reaction.  An 
event for which there is a reasonable 
possibility that there is a causal 
relationship 
between 
the 
study 
treatment and the event 
 
Unexpected 
Adverse 
Reaction.  An 
event for which the nature or severity 
is not consistent with the applicable 
product information (e.g. Investigator's 
Brochure 
for 
an 
unapproved 
investigational product or package 
insert/summary 
of 
product 
characteristics 
for 
an 
approved 
product). 
Expedited reporting of SUSARs is only 
required for events related to sacituzumab 
govitecan.  Events otherwise meeting the 
definition of SUSAR but related to TPC do 
not require expedited reporting but will be 
reported to the respective product 
manufacturers.   
 Synteract will report all relevant information 
about suspected serious unexpected adverse 
reactions (SUSARs) to all applicable 
Removal of Synteract 
information  
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regulatory authorities in all participating 
countries, and via the Eudravigilance database 
(EVCTM), as required.  SUSARs determined 
to be fatal or life-threatening must be 
submitted not later than 7 calendar days after 
initial report of the information to Synteract 
(follow-up within an additional 8 days); 
otherwise SUSARs must be submitted within 
15 calendar days.  
The Synteract will also report all SUSARs to 
the governing Ethics Committees and will 
inform all investigators, as required. 
New Text:  In this trial, the Sponsor’s 
designee is responsible for expedited 
reporting of any SAE considered to be 
SUSAR (Suspected Unexpected Serious 
Adverse Reaction). 
A SUSAR is any adverse event which meets 
the following 3 criteria  
 
Serious Adverse Event.  An event 
meeting the SAE criteria in Section 
8.1. 
 
Suspected Adverse Reaction.  An 
event for which there is a reasonable 
possibility that there is a causal 
relationship between the study 
treatment and the event 
 
Unexpected Adverse Reaction.  An 
event for which the nature or severity 
is not consistent with the applicable 
product information (e.g. Investigator's 
Brochure for an unapproved 
investigational product or package 
insert/summary of product 
characteristics for an approved 
product). 
The Sponsor’s designee will report all relevant 
information about suspected serious 
unexpected adverse reactions (SUSARs) to all 
applicable regulatory authorities in all 
participating countries, and via the 
Eudravigilance database (EVCTM), as 
required.  SUSARs determined to be fatal or 
life-threatening must be submitted not later 
than 7 calendar days after initial report of the 
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information to the Sponsor’s designee (follow-
up within an additional 8 days); otherwise 
SUSARs must be submitted within 15 
calendar days.  
The Sponsor’s designee will also report all 
SUSARs to the governing Ethics Committees 
and will inform all investigators, as required. 
9.1 Determination 
of Sample size  
Old Text: in the primary analysis population 
of patients without brain metastases (BM-ve 
population).  
New Text: as defined for the primary analysis 
in the primary analysis population of patients 
without brain metastases (BM-ve population). 
Updated for clarification 
9.2 Interim analysis Deleted Text: The DSMC reviews will 
include one planned interim analysis for 
futility of data on progression free survival 
(based on the central assessment) at 50% 
(approximately 213 events) of the required  
425 PFS events for the final analysis. For the 
interim analysis, the DSMC will be guided by 
the pre specified futility monitoring 
boundaries based on a fixed boundary of 
HR=0.999 applied to the brain metastasis 
negative population.  There is only a 0.6% 
probability that the study would falsely stop 
for futility if the true PFS HR is 0.667.  The 
DSMC will consider all available safety and 
efficacy data prior to formulating its 
recommendations regarding continuation or 
termination of the trial. If futility is not 
indicated for the primary endpoint of PFS 
brain metastasis negative population, the trial 
will continue. 
Old Text: where the 1-sided significance level 
applied is determined by 1(t) = 2-2(- z 
0.5*0.025/t). 
New Text: where the 2-sided significance 
level applied is determined by (t) = 2-2(-
z/2/t). 
 
 
 
Interim analysis for 
futility was not 
performed due to rapid 
enrollment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Typo correction: There 
was an apparent error 
with the citation of Lan-
DeMets spending 
function. The previous 
version cited the formula 
at 1-sided alpha at 0.025 
level but the formula was 
apparently mis-typed and 
corrected: the formula of 
Lan-DeMets alpha 
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Deleted Text: If OS in the ITT population is 
only tested at the final OS analysis, a 2 sided 
significance level of 0.05 will be applied to 
this endpoint.  
Added Text: The significance level for the 
final analysis of OS in the ITT population will 
be determined by the Lan-DeMets spending 
function to ensure alpha is controlled at a 2-
sided alpha of 0.05 at the final OS analysis, if 
OS analyses in the ITT population is also 
conducted at the time of PFS analysis.   
spending function at 2-
sided alpha level (0.05) is 
standard; this 
typographical error was 
corrected. 
 
 
Change to the analysis 
plan as required by the 
FDA  
9.3 Efficacy 
Analysis 
Old Text: The primary analysis population 
consists of all ITT patients without brain 
metastases labelled throughout as the BM-ve 
population, defined as all randomized patients 
who have been identified by the IRC as not 
having brain lesions at baseline.  
New Text: The primary analysis population 
consists of all ITT patients without brain 
metastases labeled throughout as the BM-ve 
population, defined as all randomized patients 
who were randomized to the strata of no 
baseline brain metastasis at the time of 
randomization.  
 
Old Text: where the 1-sided significance level 
applied is determined by 1(t) = 2-2(-
z0.5*0.025/t). 
New Text: where the 2-sided significance 
level applied is determined by (t) = 2-2(-
z/2/t). 
 
 
 
Primary analysis 
population of BM-ve 
population as defined by 
randomization strata: 
IRC does not identify 
subjects who have no 
brain lesions at baseline.  
 
 
 
 
 
 
Typo correction: There 
was an apparent error 
with the citation of Lan-
DeMets spending 
function. The previous 
version cited the formula 
at 1-sided alpha at 0.025 
level but the formula was 
apparently mis-typed and 
corrected: the formula of 
Lan-DeMets alpha 
spending function at 2-
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Old Text: If OS in the ITT population is only 
tested at the final OS analysis, a 2-sided 
significance level of 0.05 will be applied to 
this endpoint.  
New Text: The significance level for the final 
analysis of OS in the ITT population will be 
determined by the Lan-DeMets spending 
function to ensure alpha is controlled at a 2-
sided alpha of 0.05 at the final OS analysis, if 
OS analyses in the ITT population is also 
conducted at the time of PFS analysis. The 
testing procedures and corresponding alpha 
levels for type I error rate control are depicted 
in the following diagram. 
 
Old Text: FDA definitions and guidance as 
described in Guidance for Industry: Clinical 
Trials Endpoints for the Approval of Cancer 
Drugs and Biologics (May 2007) will be used.   
New Text: FDA definitions and guidance as 
described in Guidance for Industry: Clinical 
Trials Endpoints for the Approval of Cancer 
Drugs and Biologics (December 2018) and 
Clinical Trial Endpoints for the Approval of 
Non-Small Cell Lung Cancer Drugs and 
Biologics (April 2015) will be used.   
 
Old Text: or the appearance of new non-
target lesions. 
New Text: or the appearance of new lesions 
or unequivocal progression of non-target 
lesions. 
 
Old Text: Patients that progress following 
more than one missed scheduled visit will be 
censored at the last date of radiographic 
assessment without documented progressive 
sided alpha level (0.05) is 
standard; this 
typographical error was 
corrected. 
 
OS significance level: 
Change to the analysis 
plan as required by the 
FDA  
 
 
 
 
 
 
 
 
 
 
 
 
Reference to FDA 
guidelines  Clinical 
Trials Endpoints for the 
Approval of Cancer 
Drugs and Biologics are 
updated according to the 
latest version along with 
Clinical Trial Endpoints 
for the Approval of Non-
Small Cell Lung Cancer 
Drugs and Biologics 
(April 2015). 
 
Clarified reference of 
progression according to 
RECIST 1.1 
 
 
 
 
Modified censoring rule 
in the IR response per the 
FDA’s request. 
 
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disease 
New Text: Patients that progress or die 
following more than one missed scheduled 
visit will be censored at the last date of 
radiographic assessment without documented 
progressive disease 
 
Old Text: The primary analysis of PFS will 
be based on the assessment of the central 
reviewer; additional sensitivity analyses will 
be performed based the site assessment of 
PFS. 
New Text: The primary analysis of PFS will 
be based on the assessment of the central 
reviewer; additional sensitivity analyses will 
be performed based on definitions of PFS as 
defined in the Statistical Analysis Plan 
including the investigator's assessment. 
 
Old Text: Prognostic factors included in the 
analyses will be finalized prior to database 
lock and included in an addendum to the 
Statistical Analysis Plan.   
New Text: Prognostic factors included in the 
analyses will be finalized prior to database 
lock and included in the Statistical Analysis 
Plan.   
 
 
 
 
 
 
 
Multiple sensitivity 
analyses of PFS were 
defined in the SAP, 
which were clarified in 
the SAP and provided 
reference to it in the 
protocol.  
 
 
 
 
 
 
Clarification of SAP  
 
 
 
 
 
 
   
 
 
    
 
  
15 References  
New Text: Bardia A, Mayer IA, Diamond JR 
et al. Efficacy and Safety of Anti-Trop-2 
Antibody Drug Conjugate Sacituzumab 
Govitecan (IMMU-132) in Heavily Pretreated 
Patients With Metastatic Triple-Negative 
Breast Cancer. J Clin Oncol.  2017 35:2141-
2148. 
Updated missing 
references 
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15 References 
New Text: Lipscomb J et al. Patient-reported 
outcomes in cancer: a review of recent 
research and policy initiatives. CA Cancer J 
Clin. 2007; 57(5):278-300. 
Updated missing 
references 
15 References 
Deleted Text: Hammond MEH, Hayes DF, 
Dowsett M, et al. American Society of 
Clinical Oncology/College of American 
Pathologists guideline recommendations for 
immunohistochemical testing of estrogen and 
progesterone receptors in breast cancer.  J Clin 
Oncol. 2010;28:2784 95.   
Deleted unreferenced 
reference   
15 References 
Deleted Text: Mantel, N Evaluation of 
survival data and two new rank order statistics 
arising in its consideration.  Cancer 
Chemotherapy Reports. 1966;50:163 170. 
Deleted unreferenced 
reference   
Appendix 4 Study 
Calendar  
Old Text: For patients receiving TPC, 
required prior to, once during, and at the end 
of each infusion, or if administered orally, 
once at each study visit; otherwise as per local 
standard of care.  
New Text:   For patients receiving TPC, 
required prior to, once during, and at the end 
of each infusion, (Vinorelbine vital signs are 
required prior to and at the end of each 
infusion due to short infusion time) or if 
administered orally, once at each study visit; 
otherwise as per local standard of care. 
Old Text: 12Anti-drug antibodies required 
from all patients receiving IMMU-132 with 
serum samples obtained at baseline (may be 
taken at C1D1 provided it is before study drug 
administration), at Day 1 of even cycles, and 
at final study visit.  Two additional monthly 
samples for anti drug antibodies will be 
collected in the event of positive results at the 
final study visit. 
New Text: 12Anti-drug antibodies required 
from all patients receiving IMMU-132 with 
serum samples obtained at baseline (may be 
taken at C1D1 provided it is before study drug 
administration), at Day 1 of even cycles, and 
at final study visit.   
Clarification 
 
 
 
 
 
 
 
 
 
 
Clarification 
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9.3. 
Efficacy 
Analyses 
The wording of the bottom right box of the 
diagram was changed to "OS (final) in ITT, 2-
sided Lan-DeMets alpha adjusted at final" per 
FDA feedback 
Updated on August 26, 
2019 per FDA feedback 
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SYNOPSIS 
Protocol Title 
An International, Multi-Center, Open-Label, Randomized, Phase III 
Trial of Sacituzumab Govitecan (IMMU-132) versus Treatment of 
Physician Choice in Patients with Metastatic Triple-Negative Breast 
Cancer Who Received at Least Two Prior Treatments 
Sponsor 
Immunomedics, Inc., 300 The American Road, Morris Plains, NJ  07950 
Study Drug 
Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) 
composed of the humanized monoclonal antibody, hRS7 IgG1κ, which 
binds to Trop-2 (trophoblast cell-surface antigen-2); the camptothecin-
derived agent, SN-38, a topoisomerase I inhibitor; and CL2A, a linker, 
which couples SN-38 to hRS7 IgG1κ. 
Background 
Patients with triple-negative breast cancer (TNBC) who have failed 
approved or accepted treatments in the 1st and 2nd line setting remain in dire 
need of additional therapeutic approaches. The Trop-2 antigen is highly 
expressed on most solid epithelial cancers, including TNBC.  Sacituzumab 
govitecan was developed by Immunomedics to treat these cancers by 
binding to Trop-2 for targeted delivery of SN-38 directly to the tumor cell 
while minimizing systemic exposure of SN-38 to decrease host toxicity.  A 
phase I/II trial in heavily treated patients with a variety of solid cancers, 
including TNBC, demonstrated that sacituzumab govitecan was 
therapeutically active when given on days 1 and 8 of repeated 21-day 
cycles, with neutropenia being the main toxicity followed by a low 
incidence of severe diarrhea. Since 10 mg/kg was the maximum dose that 
allowed multiple cycles to be given repeatedly with acceptable toxicity, 
this dose of sacituzumab govitecan was selected for further clinical 
development with this treatment schedule, including this Phase III study. 
Objectives 
The primary objective of this study is to compare the efficacy of 
sacituzumab govitecan to the treatment of physician’s choice (TPC) as 
measured by independently reviewed progression-free survival (PFS) in 
patients with metastatic TNBC previously treated with at least two 
systemic chemotherapy regimens, and without brain metastasis at baseline. 
The secondary objectives of the study are to compare between the two 
treatment groups for: 
 Progression Free Survival (PFS) in the ITT population 
 Overall Survival (OS) in the ITT population and in the subpopulation 
of patients with brain metastasis 
 Independently-determined Objective Response Rate (ORR), duration of 
response (DoR) and time to onset of response per RECIST 1.1 criteria  
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 Quality of life 
 Safety (adverse events, safety laboratories, incidence of dose delays 
and dose reductions, treatment discontinuations due to adverse events) 
 
 
 
 
 
 
 
Treatment 
Sacituzumab govitecan (10 mg/kg intravenously on Days 1 and 8 of a 21-
day cycle) or (TPC) selected from one of the following 4 monotherapy 
treatment regimens, and administered for metastatic breast cancer, as per 
label or NCCN guidelines as per below and with dose modifications as 
provided in the protocol if too toxic   
 
Eribulin (1.4 mg/m2 intravenously on Days 1 and 8 of a 21-day cycle 
North America sites, 1.23 mg/m2 intravenously on Days 1 and 8 of a 
21-day cycle  for European sites) 
 
Capecitabine (1000-1250 mg/m2 orally twice daily on Days 1-14 of a 
21-day cycle)  
 
Gemcitabine (800-1200 mg/m2 intravenously on Days 1, 8 and 15 of a 
28-day cycle)  
 
Vinorelbine (25 mg/m2 intravenously on Day 1 weekly). (Note: 
eligible patients with Grade 2 peripheral neuropathy should not be 
prescribed vinorelbine as TPC) 
 
Scope of Study 
Approximately four hundred and eighty-eight patients (488) are anticipated 
to be enrolled. Up to approximately 150 institutions will participate in this 
study, including sites in North America, and Europe  
Study Duration 
Enrollment is expected to be completed in approximately 24 months. The 
screening period is up to 28 days (4 weeks). Patients will be treated until 
progression, death, study withdrawal, or unacceptable toxicity.  After 
discontinuation of treatment, all patients will be followed every 4 weeks 
for survival follow-up.  This may be by telephone, and will include 
documentation of any further active therapy administered for their breast 
cancer. 
Study Design 
This is an international, multi-center, open-label, randomized, Phase III 
study in patients with  either locally advanced or metastatic TNBC 
refractory or relapsing after at least 2 prior standard-of-care chemotherapy 
regimens for unresectable, locally advanced or metastatic breast cancer, 
and these regimens will qualify regardless of triple-negative status at the 
time they were given. There is no upper limit in the number of prior 
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therapies and earlier adjuvant or neoadjuvant treatment for more limited 
disease will qualify as one of the required prior regimens if the 
development of unresectable, locally advanced or metastatic disease 
occurred within 12-months of adjuvant therapy. Patients with brain 
metastasis that have been treated and are stable by MRI for at least 4 weeks 
are eligible provided they are off high-dose steroids (>20 mg prednisone or 
equivalent) for at least 2 weeks prior to randomization. (Low dose steroids 
of ≤ 20 mg daily are allowed provided dose has been stable for 4 weeks). 
All patients should have been previously treated with taxane regardless of 
disease stage (adjuvant, neoadjuvant or advanced) when it was given. 
Patients who have contra-indications or are intolerant to taxanes are 
eligible provided that they received at least one cycle of a taxane and 
showed contra-indications or  intolerance  during  or  at  the  end  of  that  
cycle. For  patients  with  a documented   germ-line   BRCA1/BRCA2   
mutation   who   received   an approved PARP inhibitor, the PARP 
inhibitor can be used to meet the criteria for one of two prior standard of 
care chemotherapies. 
Clinical sites will use standard ASCO/CAP criteria for the pathological 
diagnosis of TNBC, defined as negative for estrogen receptor (ER), 
progesterone receptor (PR) and human epidermal growth factor receptor 2 
(HER2).  Receptor results will be based on local assessment of the most 
recent biopsy findings (or other pathology reports). HER2 negative is 
defined as one of the following: 0 or 1+ by immunohistochemistry (IHC), 
or if IHC 2+, then fluorescence in situ hybridization (FISH) ratio of HER2 
gene: chromosome 17 being less than 2, as per standard guidelines. ER- 
and PR-negative is defined as < 1% of cells expressing hormonal receptors 
by IHC, as per standard guidelines. 
  A single whole-
blood sample will be also collected from all patients for determination of 
UGT1A1 genotype for retrospective assessment predicting of toxicity. 
 
 
 
 
. 
Patients meeting eligibility will be randomized 1:1 to receive either 
sacituzumab govitecan or treatment of physician choice (TPC), which 
needs to be selected prior to randomization from one of the 4 allowed 
regimens. Randomization will be stratified by number of prior 
chemotherapies for locally advanced or metastatic disease (2-3 vs >3), 
geographical location (North America vs rest of world) and known brain 
metastasis at baseline (yes or no). 
Patients will be treated until progression requiring discontinuation of 
further treatment, unacceptable toxicity, study withdrawal, or death, 
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whichever comes first.  Tumor progression leading to treatment withdrawal 
will be assessed by the investigator. Starting with the initial dose of 
sacituzumab govitecan or TPC, CT or MRI scans will be obtained every 6 
weeks for 36 weeks, then every 9 weeks thereafter, until the occurrence of 
progression of disease or unacceptable toxicity requiring discontinuation of 
further treatment.  For each patient, the same imaging technique should be 
used throughout the trial. All images will be evaluated locally at the study 
site for tumor status as per RECIST1.1. Additional CT or MRI scans may 
be performed at the discretion of the physician to assess disease status as 
medically indicated. In case of progression on clinical grounds, the 
investigator will make every effort to document progression 
objectively/radiographically, so that documentation can be reviewed by the 
IRC. Patients on either treatment arm who have progression of disease 
assessed for the first time during the study but, who, in the opinion of the 
treating physician are  deriving continued clinical benefit from IMMU-132 
or TPC treatment, relative to other available treatment options, may 
continue to be treated based on physician discretion as long as they 
continue to meet eligibility criteria. Other study procedures during 
treatment include quality of life questionnaires, physical examination and 
vital signs, CBC (with differential and platelet counts), routine serum 
chemistries, serum samples for levels of sacituzumab govitecan, 
, 
concomitant medications, and adverse events. (See Study Procedures) 
A final study visit will be conducted within 4 weeks after the last dose of 
sacituzumab govitecan or TPC for patients discontinuing study 
participation unless an earlier termination is required. Patients who 
discontinue for reasons other than progression should have a CT/MRI scan 
performed.  Patients who discontinue treatment due to toxicity will 
continue with radiologic response assessments at the protocol-required 
schedule, until progression of disease or initiation of new therapy.  The 
reason for study discontinuation will be documented and any adverse 
events or abnormal laboratories at that time will be followed until 
resolution or stabilization. 
No crossover to sacituzumab govitecan treatment will be allowed after 
discontinuing treatment in the TPC arm, but otherwise there is no 
restriction on subsequent therapies that a patient may receive after 
discontinuing the study. 
All patients, including those prematurely terminating study participation, 
will be followed every 4 weeks for survival follow-up. This may be by 
telephone and will include documentation of any further anti-cancer 
therapy they may receive. Survival status may be also documented from 
public databases (e.g., Social Security database), as allowed by local 
regulations. 
 
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Population 
Female or male patients, >18 years of age, must be able to give signed, 
written informed consent.  They must have histological or cytological 
confirmation of TNBC according to ASCO/CAP criteria as determined by 
local institution according to ASCO/CAP criteria, with locally advanced or 
metastatic disease documented by CT or MRI imaging, and currently have 
measurable disease by CT or MRI. Patients with brain metastases are 
eligible only if treated and stable by MRI for at least 4 weeks prior to 
randomization provided they are off high-dose steroids (>20 mg 
prednisone or equivalent) for at least 2 weeks. (Low dose steroids of ≤ 20 
mg daily are allowed provided the dose is stable for 4 weeks). They must 
be refractory to, or relapsed after, at least two prior standard-of-care 
chemotherapy regimens for unresectable, locally advanced or metastatic 
breast cancer and these regimens will qualify regardless of triple-negative 
status at the time they were given. There is no upper limit in the number of 
prior chemotherapies for locally advanced or metastatic disease. Adjuvant 
or neoadjuvant  therapy for early stage disease  will qualify as one of the 
required prior regimens if the development of unresectable, locally 
advanced or metastatic disease occurred within a 12-month period of time 
of adjuvant therapy.  All patients must have been previously treated with 
taxane regardless of disease stage (adjuvant, neoadjuvant or advanced) 
when it was given. Patients who have contra-indications or are intolerant to 
taxanes are eligible provided that they received at least one cycle of a 
taxane and showed contra-indications or intolerance during or at the end of 
that cycle. For patients with a documented germ-line BRCA1/BRCA2 
mutation who received an approved PARP inhibitor, the PARP inhibitor 
can be used to meet the criteria for one of two prior standard of care 
chemotherapies.  
Patients must have an ECOG performance score of 0 or 1, a 3-month life 
expectancy, adequate hematology without transfusion support (hemoglobin 
> 9 g/dL, ANC > 1,500 per mm3, platelets > 100,000 per mm3), adequate 
renal and hepatic function (creatinine clearance of > 60 ml/min, may be 
calculated using Cockcroft-Gault equation), bilirubin ≤ 1.5 IULN, AST and 
ALT ≤ 2.5 x IULN or ≤ 5 x IULN if known liver metastases), serum 
albumin ≥ 3.0 mg/dL and least 2 weeks beyond prior anti-cancer treatment 
(chemotherapy, radiotherapy and/or major surgery) or at least 3 weeks 
beyond prior antibody treatment for cancer and, with exception of alopecia 
and neuropathy (≤ Grade 2), recovered from all acute toxicities to Grade 1 
or less. 
See Protocol for additional entry requirements. 
Concomitant 
Medications and 
Procedures 
Premedication for prevention of infusion reaction with antipyretics, H1 and 
H2 blockers should be administered before sacituzumab govitecan 
infusions. Corticosteroids (50 mg hydrocortisone or equivalent P.O. or 
I.V.) may be added if necessary, and were used in approximately two-
thirds of the patients in the phase 2 trial. Premedication according to 
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established guidelines with a two or three drug combination regimen (e.g. 
dexamethasone with either a 5-HT3 receptor antagonist or a NK1 receptor 
antagonist, as well as other drugs as indicated) for prevention and treatment 
of chemotherapy-induced nausea and vomiting (CINV) is strongly 
recommended.  Additional antiemetics, sedatives, and other supportive 
measures may be employed as clinically indicated. All patients should be 
given medications for nausea and vomiting to take home after each 
infusion and instructed on use as needed.  At the onset of diarrhea, 
promptly initiate loperamide, 4 mg initially followed by 2 mg with every 
episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 
12 hours after diarrhea resolves. Additional supportive measures (e.g. fluid 
and electrolyte substitution) may also be employed as clinically indicated.  
All patients should be given take-home medications with clear instructions 
for treatment of diarrhea.  Patients who exhibit an excessive cholinergic 
response to treatment with sacituzumab govitecan (e.g., abdominal 
cramping, diarrhea, salivation, etc.) can receive appropriate premedication 
(e.g., atropine) for subsequent treatments. 
The use of such medications for patients receiving TPC is at the discretion 
of the treating physician, but must be recorded. 
All patients on study will receive aggressive medical management for 
toxicity and best supportive care, which includes the use of growth factors 
or blood transfusions, continuing or initiating the use of corticosteroids, 
other palliative medications for complications of disease (including 
medications for pain and dietary support), treatment of any active 
infections, and palliative external radiation therapy for bone metastases, or 
medications for other ongoing medical conditions. These must be recorded. 
The use of other anti-cancer treatment (besides IMMU-132 or TPC) is not 
permitted during this study.  However, palliative and/or supportive 
medications such as bone-modifying medications (bisphosphonates or 
denosumab), and/or procedures such as radiation and surgery will be 
allowed at the investigator’s discretion.  
After discontinuing the study, the patient may not receive any more 
sacituzumab govitecan; otherwise, there is no restriction on subsequent 
therapies or interventions that a patient may receive. Any further anti-
cancer therapy should be documented. 
Study Procedures 
Baseline evaluations that must be performed within 28 days of first study 
treatment include patient medical and surgical history, including all prior 
treatments for breast cancer (with best RECIST response, where available,  
and time to progression for last therapy), histology or cytology 
documentation confirming triple-negative breast cancer according to 
ASCO/CAP criteria, BRCA 1&2 mutational status, if known, CT or MRI 
imaging (chest, abdomen, pelvis, other areas of known/suspected 
involvement, with contrast as appropriate) confirming locally advanced or 
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metastatic disease, patients with brain metastasis must have a brain MRI, 
(target and non-target lesions must be determined by the clinical site at 
time of randomization),  physical examination with vital signs, concomitant 
medications, standard 12-lead ECG, CBC including platelet count (with 
WBC differential in absolute cell counts), routine serum chemistries, 
hepatitis B and C testing, serum sample for human anti-drug antibodies 
(hRS7 and SN-38) (to be frozen for shipment to Sponsor’s designee for 
analysis), whole blood sample for determination of UGT1A1 genotype, and 
quality of life assessments.  CBC including platelet count (with WBC 
differential in absolute cell counts) and serum chemistries must be repeated 
within 72 hours of cycle 1, day 1 to reconfirm eligibility.  A negative urine 
or serum pregnancy test in women of childbearing potential is required 
within 7 days prior to starting treatment.  
 
 
  
Before randomization, the managing physician must select a treatment 
choice (TPC) for each patient from one of the 4 drugs. No combination of 
the four choices is permitted. Patients then will be randomized 1:1 by 
IWRS (interactive web-based response system) to receive either 
sacituzumab govitecan (10 mg/kg on Days 1 and 8 of a 21-day cycle) or 
the preselected TPC, with stratification by number of prior treatments for 
metastatic or locally advanced disease (2-3 vs >3), geographical location 
(North America vs Rest of World), and known, baseline brain metastasis 
(yes or no). The population of patients with brain metastases will be capped 
at 15 % (N=74) of the trial patient’s population.   
Patients will be treated until progression requiring discontinuation of 
further treatment, unacceptable toxicity, study withdrawal, or death, 
whichever comes first.  All patients will receive best supportive care during 
the study, which includes continuing or initiating the use of corticosteroids, 
other palliative medications for complications of breast cancer (including 
medications for pain and dietary support), treatment of any active 
infections, and procedures such as stenting for obstructions, palliative 
external radiation therapy for bone metastases, or medications for other 
ongoing medical conditions.  Patients who discontinue treatment due to 
toxicity will continue with radiologic response assessments at the protocol-
required schedule, until progression of disease or initiation of new therapy. 
Prior to discontinuation of study treatment, patients may not receive other 
investigational antitumor agents or antineoplastic chemotherapy, or 
immunotherapy for their breast cancer. 
NCI-CTCAE v4.03 toxicity grades will be used to classify safety 
evaluations and adverse events, including serious adverse events (SAEs).  
Adverse event reporting will begin with patient number assignment at time 
of randomization and continue to 30 days after last administration of study 
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drug.  SAEs must be reported to the Sponsor’s designee within 24 hours of 
the event, and treatment-related AEs and SAEs will be followed until 
recovery or stabilization in the event of residual effects.  
In the event of an administration reaction to IMMU-132, the infusion is to 
be permanently discontinued if severe or life-threatening (Grade 3 or 4); 
otherwise, the infusion should be slowed for mild toxicity (Grade 1), and 
for moderate toxicity (Grade 2) temporarily stopped for at least 15 minutes 
or until symptoms resolve, and then resumed at the slowed rate, if the 
patient is stable. In the event of hematological or other toxicity to 
sacituzumab govitecan, patient doses may be reduced, held or permanently 
discontinued following guidelines provided in Section 6.4.4 of the 
protocol.  Use of growth factors for maintenance of dose intensity will be 
used for IMMU-132 following guidelines provided in Section 6.4.6 of the 
protocol. Use of prophylactic medications, transfusions, or other supportive 
medications are allowed as medically indicated, as best supportive care, at 
physician discretion.  Once dose-reduced for toxicity in spite of adequate 
use of supportive medications, dosing cannot be re-escalated after 
resolution of toxicity. 
In case of any administration reaction or other toxicity to TPC, patient 
doses may be reduced, held or permanently discontinued following 
guidelines provided in Section 6.4.4 of the protocol.  Use of prophylactic 
medications, including growth factors, transfusions, or other supportive 
medications are allowed as required, as best supportive care, at physician 
discretion.   
For routine safety analysis, all patients will have adverse events and 
concomitant medications (continued, changed) recorded each study visit.  
A physical examination will be obtained the first treatment day of each 
repeated treatment cycle (every 3 weeks for TPC if given weekly [e.g. 
vineorelbine]), and a pregnancy test, urinalysis and ECG will be obtained 
the first treatment day of  even cycles (every 6 weeks for TPC given 
weekly [e.g. vinorelbine]) except for Gemcitabine where pregnancy testing  
will be obtained the first treatment day of each cycle.  Vital signs will be 
obtained on each treatment day if administered intravenously or once at 
every study visit if administered orally. 
 
 
  
CBC and serum chemistries will be obtained each treatment day for 
patients receiving IMMU-132 or TPC given intravenously (eribulin, 
gemcitabine, vinorelbine). For patients receiving TPC given orally 
(capecitabine), CBC and serum chemistries will be obtained at least the 
first treatment day of each cycle and as per standard of care on other 
treatment days or study visits. In the event of ≥ Grade 3 hematological 
toxicity, CBC will subsequently be obtained more frequently at the 
discretion of the managing physician until toxicity recovers to baseline or 
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Grade 1 levels.  
Quality of life (EORTC QLQ-C30 questionnaires) will be evaluated in all 
patients at baseline, the beginning of every cycle, and the final study visit.  
 
 
 
.   
 
 
 
 
  
 
 
 
CT or MRI imaging of the chest, abdomen and pelvis (along with brain 
MRI in all patients with known baseline brain mets and other areas of 
disease previously imaged) with contrast as appropriate will be obtained in 
all patients every 6 weeks for 36 weeks, then every 9 weeks thereafter, and 
for each patient, the same imaging technique should be used throughout the 
trial. Responses identified prior to 36 weeks on study require confirmatory 
scans, which will be performed at the next scheduled scanning time-point 
(6 weeks later). For responses after 36 weeks, confirmatory scans will be 
done within 4-6 weeks of scan showing the onset of response.  Imaging 
results will be evaluated locally at each study site for tumor status as per 
RECIST1.1. Disease progression per RECIST1.1 leading to treatment 
withdrawal will be assessed by the investigator. Clinical progression 
leading to patient discontinuation should be documented also by CT/MRI 
scan of target lesions, if possible. Patients who discontinue for other 
reasons other than  progression should have a CT/MRI scan performed 
within 4 weeks from treatment discontinuation so that documentation can 
be reviewed by the IRC. Patients on either treatment arm who have 
progression of disease assessed for the first time during the study but who, 
in the opinion of the treating physician are deriving clinical benefit from 
IMMU-132 or TPC treatment relative to other available treatment options, 
may continue to be treated. 
Final study visit will be conducted 4 weeks after the last treatment dose for 
all patients discontinuing study participation, unless an early termination 
visit is required.  Patients who discontinue treatment due to toxicity will 
continue with radiologic response assessments at the protocol-required 
schedule, until progression of disease or initiation of new therapy.  The 
reason for study discontinuation will be documented and any adverse 
events or abnormal laboratories at that time will be followed until 
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resolution or stabilization. 
Note: Serum samples collected for IMMU-132 levels or anti-drug 
antibodies must be immediately frozen for storage until shipment to the 
Sponsor’s designee for analysis. 
Follow-Up 
After discontinuation of study treatment, all patients, including those 
patients prematurely terminating study treatment, will be followed every 4 
weeks for survival follow-up.  This may be by telephone, and will include 
documentation of any further active therapy administrated for their breast 
cancer.  Adverse event reporting will continue for 30 days after the last 
dose of study treatment. 
Sample Size 
A hazard ratio (HR) of 0.667, likely corresponding to a 50% improvement 
in PFS, would be considered to be clinically meaningful in this 
relapsed/refractory locally advanced or metastatic TNBC patient 
population.  Approximately four hundred and eighty-eight patients (488) 
patients are anticipated to be enrolled.  The population of patients with 
brain metastases will be capped at 15 % (N=74) of the trial population.  
The primary PFS analysis will be performed when 425 investigator defined 
PFS events have occurred in all patients randomized as long as 315 or more 
PFS events have also occurred, according IRC review, as defined for the 
primary analysis in the primary analysis population of patients without 
brain metastases (BM-ve population).  Assuming at most 15% of patients 
have brain metastases and there are 13% or fewer IRC events compared to 
investigator review, it would be expected that there would be at least 315 
IRC events in the BM-ve population at the time 425 investigator PFS 
events have been observed amongst all patients randomized.  If the true HR 
is 0.667 in the IRC review of the BM-ve population, the study will have at 
least 95% power to detect a statistically significant improvement in PFS, 
with a two-sided type 1 error rate of 5%, if data are analysed after 315 IRC 
PFS.  PFS estimates in this patient population vary from 1.7 to 4.2 months 
(3 months average).  For an estimate of median PFS of 3 months in the 
control TPC group, and assuming a 24-month enrollment period,  it is 
expected the primary PFS analysis will be performed after a minimum 
follow-up of approximately 4 months.  OS will be analysed at the time of 
the PFS analysis and also after 330 deaths have occurred in the primary 
analysis population of randomized patients without brain metastases.   The 
study will have approximately 89.5% power to detect an improvement in 
overall survival in the BM-ve population, with a two-sided 5% type 1 error 
rate, assuming that 72% of the planned number of deaths in BM-ve 
population have occurred at the time of the interim analysis (i.e., 238 
deaths), and the true HR for OS is 0.7.  Assuming a 10-month median in 
the control arm, a HR of 0.7 would likely correspond to a 4.3 month 
improvement.   The final analysis of OS is predicted to occur after a 
minimum follow-up of 17 months, 13 months after the primary analysis of 
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PFS. 
Centralized 
Procedures 
Stratified randomization will be by means of an interactive web-based 
response system (IWRS). An independent centralized blinded assessment 
of progression-free survival will be conducted for determination of the 
study primary endpoint. An independent Drug Safety and Monitoring 
Committee (DSMC) will be convened at regular intervals to assess the 
progress of this study, and review safety and progression data, per an 
approved DSMC charter.    The DSMC will consider all available safety 
and efficacy data prior to formulating its recommendations regarding 
continuation or termination of the trial. 
Data Analysis 
The primary analysis population consists of all patients without brain 
metastases, labelled throughout as the BM-ve population.  Analyses will 
also be performed amongst all randomized patients, regardless of whether 
they have brain metastases, labelled throughout as the ITT population. 
To strongly control Type I Error across populations and the two key 
endpoints of IRC PFS and overall survival (OS), a hierarchical testing 
strategy will be performed as displayed below, where a given hypothesis 
can only be declared statistically significant if all previous hypotheses in 
the hierarchy are also statistically significant.   If fewer than 30 patients 
with brain metastases are recruited, analyses in the ITT population will not 
be performed. 
 
 
Imaging evidence of efficacy will be obtained from CT or MRI scans using 
RECIST 1.1 criteria to classify tumor response, time to onset of objective 
response, duration of objective response, and time to progression. Using 
descriptive statistics, these metrics will be tabulated and compared between 
the two treatment arms.  A stratified log-rank test stratified by 
randomization strata will be used to compare the treatment groups for the 
time-to-event endpoints of Progression-Free Survival (PFS) and Overall 
Survival (OS). Estimates of hazard ratios and 95% confidence intervals of 
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PFS and OS will be based on stratified Cox proportional hazard regression 
model with treatment arm as the only covariate.  
Descriptive statistics will be used to characterize quality of life (QOL) 
questionnaire responses [EORTC QLQ C-30].  
All patients administered at least one dose of IMMU-132 or TPC will be 
included in the evaluation of safety. Safety and tolerability will be 
evaluated from adverse events, standard safety laboratories (CBC with 
differential and platelet count, serum chemistries, and urinalysis), physical 
examination, ECG and vital signs.  Adverse events will be classified 
according to the MedDRA systems of preferred terms and system organ 
class, and all adverse events and abnormal laboratories will be classified 
for severity using NCI CTCAE v4.03 toxicity grades. Descriptive statistics 
will be used to characterize adverse events, and abnormal laboratories.  
The frequency of AEs will be tabulated by MedDRA System Organ Class 
(SOC) and Preferred Term for each treatment group.  AEs leading to death 
or to discontinuation from treatment, as well as all SAEs will be 
summarized separately.  The reasons for discontinuation will also be 
summarized for each treatment group using frequency distributions. Both 
actual and change-from-baseline data on vital signs will be summarized 
using descriptive statistics by treatment group for each study time-point. 
Routine safety laboratories, based on hematology and serum chemistry 
data, will be listed by patient and summarized by descriptive statistics for 
each treatment group, if appropriate.  Laboratory test results will be graded 
according to CTCAE severity grade when applicable.  The frequency 
distribution of the worst CTCAE grade observed will be tabulated for each 
parameter by treatment group.  For parameters for which a CTCAE scale 
does not exist, the proportion of patients with abnormal values will be 
summarized by treatment group. Similarly, data on anti-drug antibody 
responses will be listed and summarized by descriptive statistics. 
Furthermore, the UGT1A1 genotype will be determined for patients 
receiving sacituzumab govitecan at baseline and compared to 
hematological toxicity and incidence of diarrhea. 
 
 
 
 
 
 
 
 
 
 
 
 
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serum concentration data.   
 
 
 
 
 
 
 
 
 
 
 
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TABLE OF CONTENTS 
PROTOCOL: IMMU132-05 ............................................................................................................1 
SUMMARY OF CHANGES ...........................................................................................................2 
SYNOPSIS  ...................................................................................................................................20 
LIST OF ABBREVIATIONS ........................................................................................................37 
1. 
INTRODUCTION ......................................................................................................39 
1.1. 
Description of the Investigational Product .................................................................39 
1.2. 
Summary of Non-Clinical and Clinical Findings .......................................................40 
1.2.1. 
Non-Clinical Studies ...................................................................................................40 
1.2.2. 
Clinical Study .............................................................................................................41 
1.2.2.1. 
Phase I .........................................................................................................................41 
1.2.2.2. 
Phase 2 ........................................................................................................................42 
1.3. 
Summary of Potential Risks .......................................................................................43 
1.4. 
Description of Study Population .................................................................................43 
1.5. 
Rationale for Dose Regimen .......................................................................................44 
2. 
STUDY OBJECTIVES ..............................................................................................44 
2.1. 
Primary Objective .......................................................................................................44 
2.2. 
Secondary Objectives .................................................................................................44 
3. 
STUDY DESIGN .......................................................................................................45 
3.1. 
Study Overview ..........................................................................................................45 
3.2. 
Data Safety Monitoring Committee (DSMC) .............................................................48 
4. 
PATIENT POPULATION ..........................................................................................48 
4.1. 
Inclusion Criteria ........................................................................................................48 
4.2. 
Exclusion Criteria .......................................................................................................50 
4.3. 
Concomitant Medications and Procedures .................................................................51 
4.4. 
Patients receiving anticoagulants ................................................................................52 
4.5. 
Patients receiving QT prolonging drugs .....................................................................53 
5. 
STUDY PROCEDURES ............................................................................................54 
5.1. 
Informed Consent .......................................................................................................54 
5.2. 
Patient Registration .....................................................................................................54 
5.3. 
Pre-Study/Baseline Evaluations (see Study Calendar, Appendix 4) ..........................54 
5.4. 
Procedures During Treatment (see Study Calendar, Appendix 4) .............................55 
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5.6. 
Final Study Evaluation or Unscheduled/Early Termination Visit ..............................58 
5.7. 
Long-Term Follow-Up ...............................................................................................58 
5.8. 
Criteria for Removal from Protocol Treatment ..........................................................58 
5.9. 
End of Study ...............................................................................................................59 
6. 
STUDY DRUG INFORMATION ..............................................................................59 
6.1. 
Description of Study Drug ..........................................................................................59 
6.2. 
Drug Accountability ...................................................................................................60 
6.3. 
Study Drug Preparation ..............................................................................................60 
6.4. 
IMMU-132 Treatment ................................................................................................60 
6.4.1. 
Preventative Medications ............................................................................................61 
6.4.2. 
Vital Signs ..................................................................................................................61 
6.4.3. 
Intravenous Administration of IMMU-132 ................................................................61 
6.4.4. 
Managing IMMU-132 Infusion Toxicity ....................................................................62 
6.4.5. 
IMMU-132 Dosing Schedule .....................................................................................64 
6.4.6. 
IMMU-132 Dose Reduction and Termination Guidelines .........................................64 
6.5. 
Treatment of Physician Choice (TPC) ........................................................................67 
6.5.1. 
Eribulin (Halaven) ......................................................................................................70 
6.5.2. 
Capecitabine (Xeloda) ................................................................................................71 
6.5.3. 
Gemcitabine (Gemzar) ................................................................................................71 
6.5.4. 
Vinorelbine (Navelbine) .............................................................................................72 
6.6. 
Management of Nausea and Vomiting for the TPC arm ............................................74 
7. 
STUDY EVALUATIONS ..........................................................................................74 
8. 
ADVERSE EVENTS..................................................................................................75 
8.1. 
Serious Adverse Events (SAEs) .................................................................................75 
8.2. 
Reporting AEs/SAEs ..................................................................................................76 
8.3. 
Recording Information on AEs ...................................................................................77 
8.4. 
Grading of AE Severity ..............................................................................................77 
8.5. 
Pregnancy ...................................................................................................................78 
8.6. 
Follow-up of Unresolved AEs ....................................................................................78 
8.7. 
Expedited Reporting ...................................................................................................78 
8.8. 
Reporting death ...........................................................................................................78 
8.9. 
Reporting to IRB/Ethics Committee (EC) ..................................................................79 
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8.10. 
Reporting to Health Authorities ..................................................................................79 
9. 
STATISTICAL CONSIDERATIONS .......................................................................79 
9.1. 
Determination of Sample Size ....................................................................................79 
9.2. 
Interim analysis ...........................................................................................................80 
9.3. 
Efficacy Analyses .......................................................................................................80 
9.4. 
Safety Analyses ..........................................................................................................86 
 
 
 
 
10. 
TREATMENT COMPLIANCE .................................................................................87 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................87 
12. 
DATA HANDLING AND RECORD KEEPING ......................................................88 
12.1. 
Electronic Case Report Forms (eCRFs) .....................................................................88 
12.2. 
Record Retention ........................................................................................................88 
13. 
ADMINISTRATIVE REQUIREMENTS ..................................................................88 
13.1. 
Good Clinical Practice ................................................................................................88 
13.2. 
Ethical Considerations ................................................................................................89 
13.3. 
Patient Information and Consent ................................................................................89 
13.4. 
Protocol Compliance ..................................................................................................90 
13.5. 
Site Monitoring and On-Site Audits ...........................................................................90 
13.6. 
Patient Data Protection ...............................................................................................90 
13.7. 
Financial Disclosure ...................................................................................................91 
13.8. 
Sponsor Discontinuation Criteria ...............................................................................91 
14. 
DISSEMINATION AND PUBLICATION OF RESULTS .......................................92 
15. 
REFERENCES ...........................................................................................................93 
 
LIST OF TABLES 
Table 1: 
Incidence of Drug-Related Grade 3+ Adverse Events at 10 mg/kg IMMU-
132 ..............................................................................................................................42 
Table 2: 
Drug-related adverse events in TNBC patients. .........................................................42 
Table 3: 
IMMU-132 Preparation for 10 mg/kg Dosing (Assumes 70-kg Patient) ...................60 
Table 4: 
Infusion Rate Guidelines For Patients Remaining Stable in Absence of 
Hypersensitivity or Infusion-Related Events ..............................................................62 
Table 5: 
Recommended Medications for Nausea, Vomiting and Diarrhea* ............................63 
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Table 6: 
IMMU-132 ..................................................................................................................65 
Table 7: 
Reporting Requirements For Adverse Events ............................................................77 
Table 8: 
Grading Of Adverse Event Severity ...........................................................................77 
Table 9: 
Anticipated toxicities of IMMU-132 and control drugs .............................................85 
 
LIST OF FIGURES 
Figure 1: 
Progression-free survival and overall survival ...........................................................43 
 
LIST OF APPENDICES 
APPENDIX 1. LIST OF STANDARD TREATMENTS FOR TNBC .......................................96 
APPENDIX 2. PERFORMANCE STATUS EVALUATION ...................................................97 
APPENDIX 3. PROCEDURE FOR COLLECTION, STORAGE, AND SHIPMENT 
OF SAMPLES ............................................................................................................99 
APPENDIX 4. STUDY CALENDAR ......................................................................................100 
APPENDIX 5. EORTC QLQ-C30 (VERSION 3) ....................................................................103 
APPENDIX 6. RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
(RECIST) 1.1 ............................................................................................................105 
APPENDIX 7. CHILD-PUGH SCORE IN PATIENTS WITH HEPATIC 
IMPAIRMENT .........................................................................................................108 
 
 
 
 
 
 
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LIST OF ABBREVIATIONS 
AE 
 
adverse event 
ADC 
 
antibody-drug conjugate 
ADCC 
 
antibody-dependent cell-mediated cytotoxicity 
ALT 
 
 
alanine aminotransferase 
ANC  
 
absolute neutrophil count 
AST 
 
aspartate aminotransferase 
AUC 
 
area under the curve 
HCG 
 
beta human chorionic gonadotropin 
BM -ve 
 
Brain metastases negative (no brain metastases at baseline/randomization) 
BUN 
 
blood urea nitrogen 
CBC  
 
complete blood count 
CDC  
 
complementary-dependent cytotoxicity 
CDR  
 
complementarity-determining region 
CFR 
 
 
Code of Federal Regulation 
CNS  
 
central nervous system 
CR 
 
 
complete response 
CRF 
 
 
case report form 
CT 
 
 
computed tomography imaging 
CTCAE 
 
common terminology criteria for adverse events 
DNA  
 
deoxyribonucleic acid 
DLT 
 
 
dose-limiting toxicity 
DSMC  
 
Drug Safety and Monitoring Committee 
ECG  
 
electrocardiogram 
EORTC 
 
European Organization for Research and Treatment of Cancer 
FDA  
 
Food and Drug Administration 
GCP  
 
good clinical practice 
GI 
 
gastrointestinal 
HAHA 
 
human anti-human antibody 
HIPAA 
 
Health Insurance Portability and Accountability Act of 1996 
HIV   
 
human immunodeficiency virus 
IATA  
 
International Air Transport Association 
ICH 
 
 
International Committee on Harmonization 
IEC  
 
 
independent ethics committee  
IgG 
 
immunoglobulin G 
IND 
 
 
Investigational New Drug 
IRB 
 
Institutional Review Board 
IRC 
 
Independent Review Committee 
IULN 
 
institutional upper limit of normal  
IMMU-132 
 
Company Code for  sacituzumab govitecan 
LA  
 
Locally advanced 
LDH  
 
lactate dehydrogenase 
mAb  
 
monoclonal antibody 
MRI 
 
 
magnetic resonance imaging 
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MTD  
 
maximum tolerated dose 
NSAE  
 
non-serious adverse event 
NCI 
 
 
National Cancer Institute 
NSCLC 
 
non-small cell lung cancer  
NSAID 
 
non-steroidal anti-inflammatory drug  
OR 
 
 
Objective Response, OR = CR + PR 
ORR  
 
Objective (overall) response rate 
OS 
 
 
overall survival 
PBS 
 
 
phosphate-buffered saline 
PD 
 
 
progressive disease 
PFS 
 
 
progression-free survival 
PK 
 
 
pharmacokinetics 
PR 
 
 
partial response 
QLQ-30 
 
quality of life questionnaire version 30 
RECIST 1.1 
 
Response Evaluation Criteria in Solid Tumors version 1.1 
RBC  
 
red blood cell 
SAE 
 
serious adverse event 
SCLC  
 
small cell lung cancer 
SD  
 
 
stable disease 
TNBC  
 
Triple-Negative Breast Cancer 
TPC 
 
 
treatment of physician’s choice 
Trop-2  
 
Trophoblastic cell-surface antigen  
TTP 
 
 
time to progression 
WBC 
 
white blood cells 
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1. 
INTRODUCTION 
1.1. 
Description of the Investigational Product 
SN-38, a topoisomerase I inhibitor, is the active metabolite of irinotecan, which is approved as a 
single agent for colorectal cancer and included in treatment regimens such as FOLFIRI 
(Zaanan 2011).  Only 5% of irinotecan is converted to the active SN-38 form by esterase activity 
residing primarily in the liver, albeit there are esterases in the tumor that can cleave irinotecan to 
SN-38 (Mathijsen 2001). Its catabolism in the liver results in its transport through the bile duct 
into the intestines, resulting in GI toxicity. 
In an attempt to improve the bioavailability of SN-38, Immunomedics, Inc. developed a 
procedure for coupling SN-38 to an antibody that retains the antibody molecular integrity and 
specific binding (Govindan 2009; Moon 2010).  In murine models bearing human tumor 
xenografts, one particular linker with an SN-38 release half-life of 1.0 to 1.5 days was found to 
have the best therapeutic response.   Importantly, significant anti-tumor effects were possible at 
doses that were completely non-toxic to the mice.   
Sacituzumab govitecan (Company Code: IMMU-132) is an antibody-drug conjugate (ADC) 
composed of the following three compounds: 
1. The humanized monoclonal antibody, hRS7 IgG1, binds to Trop-2 (trophoblastic cell-
surface antigen, also known as EGP-1, epithelial glycoprotein-1).  It is a cell surface, 
transmembrane calcium signal transducer glycoprotein belonging to the TACSTD gene 
family that is highly expressed in many epithelial cancers, particularly metastatic sites 
(Alberti 2007), with much lower expression in normal tissues (Trerotola 2010).  Trop-2 
has been implicated in oncogenesis, often being found in more aggressive tumors 
(Fang 2009).  The antibody was initially developed as a murine monoclonal antibody by 
the immunization of mice with a fresh specimen of a human lung cancer.  The properties 
of the parent murine antibody have been extensively described (Basu 1995; Stein 1994; 
Shih 1995; Stein 1993; Stein 1995; Stein 1997). 
2. The camptothecin-derived agent, SN-38, a topoisomerase 1 inhibitor.  
3. A linker, with the company designation, CL2A, which binds SN-38 to the antibody. 
IMMU-132 is prepared at a ratio of 7 to 8 molecules of SN-38 per molecule of the anti-Trop-2 
antibody, hRS7 (Goldenberg 2015).  For clinical use, 10 mg/mL are formulated in 25 mM MES 
buffer, pH 6.5, together with the other excipients (25 mM trehalose, 0.01% Polysorbate 80).  It is 
then lyophilized at 200 mg/vial.  IMMU-132 is supplied in 50-mL clear glass vials to be stored 
under refrigerated conditions (2-8oC) until used.  Since the formulated drug product contains no 
preservative, vials should be used only once and within eight hours of reconstitution.   
Each 200 mg vial of IMMU-132 is reconstituted with 20 ml of saline and then further diluted 
with saline for intravenous administration so that the final concentration of IMMU-132 is in the 
1.1-3.4 mg/ml range.  
IMMU-132 should be administered at a starting dose of 10 mg/kg on days 1 and 8 of a 21-day 
cycle.  Dose reductions and dose delays are linked to certain toxicity. 
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1.2. 
Summary of Non-Clinical and Clinical Findings 
1.2.1. 
Non-Clinical Studies 
The anti-tumor activity of the hRS7-SN-38 conjugate was examined in mice bearing 
a variety of human epithelial cancer xenografts, where it was shown to have significant 
anti-tumor effects compared to free SN-38, irinotecan, or an irrelevant IgG-SN-38 conjugate 
(Cardillo 2011; Goldenberg 2015; Cardillo 2015). There were significant changes in liver 
transaminases that were returning to normal levels 2 weeks after treatment in mice 
(Cardillo 2011). 
While Trop-2 is highly conserved among various species, the hRS7 antibody does not bind to 
murine Trop-2, but an immunohistology study of cynomolgus monkey tissues showed hRS7 
bound to Trop-2 and had a similar distribution as found in humans (Cardillo 2011).  Thus, a 
toxicology study was performed with IMMU-132 in monkeys with the purpose to assess the 
dose-limiting toxicity and to determine if Trop-2 expressing normal tissues would limit the use 
of this conjugate.  Two doses were administered within one week (3 days apart) at a cumulative 
amount of 120 and 240 mg/kg (1.92 and 3.84 mg/kg of SN-38; human equivalent dose of the 
conjugate was 38.7 and 77.4 mg/kg).  Pharmacokinetic analysis of the clearance of the hRS7 IgG 
and SN-38 (as free SN-38, total SN-38, and a derived IgG-bound SN-38) showed the IgG cleared 
at what appeared to be an expected rate (e.g., 30% cleared over 1 day, terminal half-life ~5 days).  
The clearance parameters for the total and IgG-bound SN-38 were very similar, with a half-life 
of ~13 h, which reflects the clearance of the IgG and the fact that the SN-38 is released from the 
conjugate at a rate of ~50% every 20 h.  As expected, the AUC for the total and IgG-bound SN-
38 was nearly 15-times higher than the free SN-38, which had a half-life of ~25 h, similar to the 
rate reported for SN-38 released from irinotecan.  Thus, the conjugate is capable of liberating 
low concentrations of SN-38 in the serum at a slow and sustained rate.   
In cynomolgus monkeys administered the cumulative dose of 120 mg/kg, there was evidence of 
myelosuppression within 3 days, but the decrease in counts did not achieve gradable levels and 
were completely restored within 10-14 days.  No significant change in serum chemistries or 
tissue pathology was noted.  At the 240 mg/kg, severe gastrointestinal (GI) and hematological 
toxicities occurred; therefore, the maximum tolerated dose had been exceeded.  The conjugate 
displayed a similar toxicity profile as irinotecan, with major GI and hematological toxicity.  
Importantly, there were no serious histopathological changes to tissues with known hRS7 
binding in the monkey, with the exception of mild to moderate hemorrhage of the endometrium 
and atrophy of the endometrial glands that were showing recovery at the time the study was 
terminated.  (See Investigator Brochure for additional information on IMMU-132) 
In vitro studies in 2 triple-negative breast cancer cell lines, one expressing Trop-2 and another 
being Trop-2-negative, showed that double-stranded DNA breaks only occurred in the Trop-2- 
expressing cell line after a brief exposure (1 h) with IMMU-132 (Goldenberg 2015).  This study 
confirmed that SN-38 delivery by the specific IMMU-132 conjugate was necessary for the 
therapeutic effect, with a non-targeting conjugate having nearly 3-fold less double-stranded DNA 
breaks than IMMU-132-treated Trop-2-expressing cells.  In mice bearing Trop-2-expressing 
human tumor xenografts that were given irinotecan or IMMU-132, SN-38 levels in the tumors 
exposed to IMMU-132 were as much as 130-fold more than in the irinotecan-treated animals, 
illustrating the superior targeting of the conjugate to deliver SN-38 to tumors (Sharkey 2015).  In 
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addition, these studies showed that the SN-38 was protected from glucuronidation while coupled 
to the IgG, and since the linker was coupled to SN-38’s lactone ring, this also preserves SN-38 in 
its most active form until it is released from the conjugate. This reduced glucuronidation is 
believed to explain the low incidence of severe diarrhea found in the clinical trials. Thus, 
IMMU-132 appears to be a more effective vehicle for delivering SN-38 than irinotecan, and 
potentially less toxic in terms of severe diarrhea.  
1.2.2. 
Clinical Study 
Study IMMU-132-01 entitled “A Phase I/II Study of IMMU-132 (hRS7-SN38 Antibody-Drug 
Conjugate) in Patients with Epithelial Cancer,” conducted under IND 115621 (ClinicalTrials.gov 
identifier, NCT01631552), is the only ongoing clinical investigation of the safety and efficacy of 
IMMU-132 in patients with cancer. This is a Phase I/II, open-label multi-center, US-only, study 
of IMMU-132 in previously-treated patients with advanced, metastatic, epithelial tumors. The 
primary objective of this study is to evaluate the safety and tolerability of IMMU-132 as a single 
agent administered in 3-week treatment cycles, in previously-treated patients with advanced 
epithelial cancer.  The secondary objectives are to obtain initial data concerning 
pharmacokinetics, immunogenicity, and efficacy with this dosing regimen.   
Briefly, the study population is constituted of males or non-pregnant, non-lactating, females ≥ 18 
years of age, able to give written informed consent, if they have documented epithelial cancer 
that involves any of the following tumor types: ovarian, cervical, endometrial, breast (triple-
negative and non-triple-negative), prostate (hormone refractory), lung [non-small cell (NSCLC) 
and small cell (SCLC)], head and neck (squamous cell), esophageal, colorectal, gastric, pancreas, 
renal (clear cell), urothelial, hepatocellular, glioblastoma multiforme and thyroid (follicular) 
cancers.  There is no Trop-2 selection for enrollment.  Patients must have metastatic disease and 
have either relapsed after receiving or were refractory to at least one standard chemotherapy 
regimen for their disease, with measurable disease by CT or MRI at the time of treatment, but no 
single lesion ≥ 7 cm in diameter.  
1.2.2.1. 
Phase I  
In the completed Phase I portion of Study IMMU-132-01, doses as high as 18 mg/kg were given 
on day 1 and 8 of a 21-day treatment cycle (Starodub 2015).  Neutropenia was the dose-limiting 
toxicity at this level, with the MTD declared to be 12 mg/kg. Most of the other adverse events at 
all dose levels were Grade 2 or lower.  Fatigue, alopecia and occasional mild to moderate 
diarrhea were some of the more common non-hematological toxicities, with two patients 
reporting a rash.  While 12 mg/kg was considered the MTD, there was tendency for patients 
treated at this level to have delays in their dose schedule, as well as dose reductions.  Therefore, 
in order to continue treatment with minimal delays or reductions, IMMU-132 treatment starting 
at either 8 or 10 mg/kg (days 1 and 8 of a 21-day cycle) was selected for evaluation in the Phase 
II portion of this study,  with particular emphasis to enroll patients with triple-negative breast, 
small and non-small cell lung cancers, and secondarily patients with esophageal and urothelial 
cancers.  
Table 1 below indicates the incidence of drug-related grade 3+ adverse events observed at 10 
mg/kg in all patients/all tumors enrolled at the 10 mg/kg dose level.  Most frequent drug-related 
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grade 3+ adverse events were neutrnpenia (18%), diaIThea (6%), febrile neutropenia (5%), 
fatigue (5%), leukopenia (5%) and anemia (4%). 
Table 1: 
Incidence of Drug-Related Grade 3+ Adverse Events at 10 mg/kg IMMU-132 
10 mg/kg (N = 109) 
Neutropenia 
18% 
Dianhea 
6% 
Feb1ile neutropenia 
5% 
Fatigue 
5% 
Leukopenia 
5% 
Anemia 
4% 
1.2.2.2. 
Phase 2 
As of June 30, 2017, 110 patients with relapsed/refracto1y TNBC were treated with sacituzumab 
govitecan 10 mg/kg on days 1 and 8 every 21 days until progression or unacceptable toxicity. 
The age range of all patients was from 31 to 81 years old with a median age of 5 5 years old. The 
patient population were heavily pre-treated; 59% of patients were treated in the 4th line setting 
and beyond. Some patients received up to 10 prior therapies and 75% of patients had received 
prior platinum agents. 
The most common adverse events were neutropenia, nausea, and dianhea (see Table 2). Most 
adverse events were managed with suppo1iive medication or dose modifications. Majority of 
patients were able to continue at the 10 mg/kg dose, 25% of patients had dose modifications, 
predominantly to 7.5 mg/kg. Only two patients discontinued treatment due to adverse events 
(grade 3 transient infusion reaction and grade 2 fatigue). There were no treatment-related deaths. 
Table 2: 
Drug-related adverse events in TNBC patients. 
Body system 
Adverse event (AE) 
All grades 
Grade 3 or 4 
Hematologic 
Gastrointestinal 
Other 
Neutropenia 
Febrile neutropenia 
Anemia 
Leukopenia 
Nausea 
Dian-hea 
Vomiting 
Constipation 
Fatigue 
Alopecia 
Decreased appetite 
Hyperglycemia 
Hypomagnesemia 
Hypophosphatemia 
Interim Summary of Efficacy (Bardia 2015, Bardia 2017) 
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63% 
8% 
52% 
24% 
63% 
56% 
46% 
32% 
50% 
36% 
30% 
23% 
21% 
15% 
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7% 
10% 
14% 
5% 
8% 
5% 
1% 
7% 
NA 
0% 
4% 
1% 
8% 
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Out of 110, 102 patients were assessable. Three patients achieved complete responses and 34 
partial responses, for an objective response rate of 34% by the investigator (RECIST 1.1). Six 
patients achieved CR  and 28 patients achieved PR by the blinded independent central review, for 
an objective response rate of 31%.  Clinical benefit rate (CR+PR+SD ≥6 months)  was 45% 
(50/110). 74% (75/102) of patients experienced a reduction of target lesions (sum of diameters). 
8 patients withdrew prior to assessment (4 PD, 4 MRI brain metastases). The median time to 
onset of response was 2 months with a median duration of response of 7.6 months. Importantly, 
9 patients were progression free for more than 1 year from start of treatment  including 4 patient 
for 2 to 3 years and 12 patients were continuing treatment as of June 30, 2017 data cut-off. The 
median PFS was 5.5 months and the median OS was 12.7 months at the data cutoff date of June 
30, 2017. Patients benefit from sacituzumab govitecan treatment irrespective of age, onset of 
metastatic disease, or number of prior regimens. 
Figure 1: 
Progression-free survival and overall survival 
 
 
1.3. 
Summary of Potential Risks 
In patients with TNBC, the following adverse events (AEs), all grades and regardless of 
relationship to IMMU-132, have been observed at the following rates (by order of frequency in 
each category): 
 Very likely: (> 40%): nausea, vomiting, diarrhea, neutropenia, anemia, fatigue 
 Likely (20%-39%): alopecia, constipation, decreased appetite, leukopenia  
 
hyperglycemia, hypomagnesemia  
 Less Likely (10%-<20%): hypophosphatemia, febrile neutropenia 
1.4. 
Description of Study Population 
TNBC is a serious disease, with an annual incidence estimated to be about 40,000 people (20,000 
for metastatic TNBC) in the United States, and with a median survival of 10-13 months for 
metastatic TNBC (Andre 2012).  This incidence is based upon the estimate that between 10% 
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100 
80 
en 
40 
,o 
0 
Number at risk 
11ln 
Progression-free survival 
Median (95% Cl): 5.5 months (4.8, 6.6) 
85/ LJO (nrt,J number of events 
en 
8 
Months 
1R 
12 
,n 
16 
80 
en 
40 
,o 
Nt.mber at risk 
110 
Overall survival 
Median (95% a): 12.7 months (10.8, 13.6) 
71/ 110 (64Yo) deaths reported 
en 
12 
Months 
'7 
l S 
18 
21 
1S 
" 
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and 20% of women with breast cancer have TNBC, since their tumors do not express estrogen 
receptor, progesterone receptor, or HER2/neu (Mancini 2014). Therefore, metastatic TNBC is 
insensitive to most of the available targeted therapies for breast cancer treatment, including 
HER2-directed therapy (such as trastuzumab), and endocrine therapies (such as tamoxifen or the 
aromatase inhibitors).  
There is currently no single standard chemotherapy to treat patients with relapsed/refractory 
metastatic TNBC. Duration of response is usually short, with rapid relapse, and visceral and 
brain metastases being very common. 
In TNBC patients treated with capecitabine, median PFS was 1.7 months (Perez 2010), and it 
was 2.9 months for gemcitabine combined with carboplatin in patients treated with up to 2 prior 
chemotherapies (O’Shaughnessy 2014).  
In a small cohort of 22 second-line TNBC patients (33% chemotherapy-naïve and one median 
prior chemotherapy regimen) treated with nab-paclitaxel, median PFS was 3.7 months (Forero-
Torres 2015).  
Median PFS was 2.9 months in 86 metastatic TNBC patients treated with cisplatin or 
carboplatin, and who received no more than one prior chemotherapy (Isakoff 2015). 
1.5. 
Rationale for Dose Regimen  
Most patients in IMMU-132-01 study have been treated with 8 or 10 mg/kg doses. There was no 
major difference in safety between these two doses, but there was a trend for better efficacy with 
10 mg/kg dosing, which was therefore selected for this study. 
2. 
STUDY OBJECTIVES 
2.1. 
Primary Objective 
The primary objective of this study is to compare the efficacy of sacituzumab govitecan to the 
TPC as measured by independently-reviewed IRC PFS in patients with locally advanced or 
metastatic TNBC previously treated with at least two systemic chemotherapy regimens for 
unresectable, locally advanced or metastatic disease, and without brain metastasis at baseline.   
2.2. 
Secondary Objectives 
The secondary objectives of the study are to compare between the two treatment groups for: 
 PFS for the ITT population 
 OS in both the ITT population and in the subgroup with brain metastasis. 
 Independently-determined Objective Response Rate (ORR), duration of response and 
time to onset of response according to RECIST 1.1 criteria 
 Quality of life 
 Safety, including adverse events, safety laboratories and evaluations, incidence of 
dose delays and dose reductions, and treatment discontinuations due to adverse events 
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3. 
STUDY DESIGN 
3.1. 
Study Overview 
This is a Phase III, randomized, open-label, multicenter (up to 100 centers) study of IMMU-132 
in locally-advanced or metastatic TNBC patients who are refractory or relapsing after at least 2 
prior standard chemotherapy regimens  for unresectable, locally advanced or metastatic breast 
cancer, and these regimens will qualify regardless of triple-negative status at the time they were 
given. A table of approved or standard therapeutic regimens for TNBC is included in 
Appendix 1.  There is no upper limit in the number of prior therapies. Earlier adjuvant or 
neoadjuvant treatment for more limited disease will qualify as one of the required prior regimens 
if the development of unresectable, locally advanced or metastatic disease occurred within a 12-
month period of time after completion of chemotherapy. All patients must have been previously 
treated with taxane regardless of disease stage (adjuvant, neoadjuvant or advanced) when it was 
given. Patients who have contra-indications or are intolerant to taxanes are eligible provided that 
they received at least one cycle of a taxane and showed contra-indications or intolerance during 
or at the end of that cycle. For patients with a documented germ-line BRCA1/BRCA2 mutation 
who received an approved PARP inhibitor,  the PARP inhibitor can be used to meet the criteria 
for one of two prior standard of care chemotherapies. 
Approximately four-hundred eighty-eight (488)patients from up to approximately 150 centers, 
including sites in North America, and Europe will be randomized 1:1 to the following treatment 
arms: 
 Sacituzumab govitecan (10 mg/kg on Days 1 and 8 of 21-day cycles) 
 TPCdetermined before randomization from only one of the following 4 treatment 
regimens, and administered for metastatic breast cancer as per label or NCCN 
guidelines below or with dose modifications if too toxic (see Section 6.5). No 
combination of the four choices is permitted. 
 Eribulin (1.4 mg/m2 intravenously on Days 1 and 8 of a 21-day cycle for North 
America sites, 1.23mg/m2 intravenously on Days 1 and 8 of a 21-day cycle  for 
European sites) 
 Capecitabine (1000-1250 mg/m2 orally twice daily on Days 1-14 of a 21-day 
cycle) 
 Gemcitabine (800-1200 mg/m2 intravenously on Days 1, 8 and 15 of a 28-day 
cycle) 
 Vinorelbine (25 mg/m2 intravenously on Day 1 weekly (Note: eligible patients 
with Grade 2 peripheral neuropathy should not be prescribed vinorelbine as TPC) 
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Patients will be stratified at randomization by: 
 Number of prior treatments for advanced disease (2-3 vs >3) 
 North America vs Rest of World 
 Known, baseline brain metastasis (yes or no)  
Patients will be treated until progression requiring discontinuation of further treatment, 
unacceptable toxicity, study withdrawal, or death, whichever comes first.  Tumor progression 
leading to treatment withdrawal will be assessed by the investigator. Patient who discontinue 
treatment for other reasons than PD should a MRI/CT scan performed within 4 weeks of study 
treatment discontinuation.  No crossover to IMMU-132 treatment will be allowed at time of 
progression in the TPC arm. 
Clinical sites will use standard ASCO/CAP criteria for the pathological diagnosis of TNBC, 
defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal 
growth factor receptor 2 (HER2).  Receptor results will be based on local assessment of the most 
recent analyzed biopsy (or other pathology specimen). HER2 negative is defined as one of the 
following: 0 or 1+ by immunohistochemistry (IHC), or if IHC 2+, then fluorescence in situ 
hybridization (FISH) ratio of HER2 gene: chromosome 17 being less than 2, as per standard 
guidelines (Wolff 2013). ER- and PR-negative is defined as < 1% of cells expressing hormonal 
receptors by IHC, as per standard guidelines (Hammond 2010).  
 
 
 
 
 
 
 
This study will utilize an intent-to-treat analysis.  
Screening evaluations within 28 days of the scheduled start of treatment include signature of 
informed consent, patient eligibility determination, BRCA 1&2 mutational status, if known, 
medical/surgical history, physical examination with vital signs and performance evaluation, prior 
and concomitant medications, local histology review to confirm TNBC diagnosis, CT or MRI 
scans (chest, abdomen, pelvis, with contrast as appropriate) with additional imaging of other 
involved/suspected areas. Patients with known or suspected brain metastasis must have a brain 
MRI and must be documented to have had stable CNS disease for at least 4 weeks  Target and 
non-target lesions must be determined by the clinical site at time of randomization. CBC 
(including platelet count, with WBC differential in absolute cell counts), routine serum 
chemistries, urinalysis, ECG and serum samples for anti-drug antibodies will be also performed.  
In women of childbearing potential, a urine or serum HCG is also required within one week of 
treatment.  CBC (including platelet count, with WBC differential in absolute cell counts), routine 
serum chemistries will be repeated within 72 hours of cycle 1, day 1 to ensure eligibility. 
IMMU-132 (10 mg/kg) is administered in 21-day treatment cycles with once-weekly dosing the 
first two weeks (days 1 and 8) and no dosing the third week.  Dosing is based on patient’s body 
weight on Day1 of each cycle (or at each dosing day if change in body weight is > 10% or if 
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required by institutional policy). TPC dosing is based upon body surface area as per local 
standard of care. Treatment of all patients may continue until subsequent imaging  documents 
disease progression from the pre-study assessment requiring discontinuation.  NCI CTCAE 
v4.03 is used to grade all adverse events and to provide dose reduction, delay or cessation 
guidelines in the event of treatment-related toxicity.  Growth factors and other supportive care 
are allowed and are strongly encouraged to be used aggressively including for prophylaxis when 
medically necessary any time during treatment with IMMU-132 or the TPC.  Refer to guidelines 
in Section 6.4.6 and Table 6. 
Toxicity guidelines for patients receiving TPC should follow local standard of care. If a patient 
randomized to receive IMMU-132 experiences ≥ Grade 2 neutropenia or ≥ Grade 2 GI toxicity 
prior to starting on the first treatment day (Cycle 1 Day 1), the treatment initiation should be 
withheld until resolved to ≤ Grade 1.  If recovery to ≤ Grade 1 requires more than a 3-week 
delay, the patient should come off the study. In subsequent treatment cycles, if a patient  
experiences ≥ Grade 3 neutropenia or ≥ Grade 3 GI toxicity, IMMU-132  should be withheld 
until resolved to ≤ Grade 1 and patients will be assessed at least weekly (biweekly for Grade 4 
toxicities).  If recovery to ≤ Grade 1 requires more than a three-week delay, the patient should 
come off the study. IMMU-132 will be permanently discontinued for a patient in the event of 
any ≥ Grade 3 infusion reactions which occurs after pre-medication with antihistamines, H2 
blockers and steroids. In the event of other ≥ Grade 3 treatment-related toxicity at the time of a 
scheduled treatment day, IMMU-132 will be held and patients will be assessed at least weekly 
(biweekly for Grade 4 toxicities).  If recovery to ≤ Grade 1 delays the next dose by only one 
week, treatment may resume without dose reduction; however, patients should be administered 
growth factor support such as gCSF.  If recovery of non-hematologic toxicity to ≤ Grade 1 
delays the next dose by 2 or 3 weeks, treatment must be resumed at a reduced dose (see Table 6).  
If recovery to ≤ Grade 1 requires more than three weeks delay, treatment must be permanently 
discontinued.  If recovery of hematologic toxicity (neutropenia) to ≤ Grade 1 delays the next 
dose by 1 week, growth factors should be added as per Section 6.4.6, or as medically necessary 
to prevent dose delays and dose reduction.  
Patients who exhibit an excessive cholinergic response to IMMU-132 or TPC treatment (e.g., 
abdominal cramping, diarrhea, salivation, etc.) can receive appropriate premedication (e.g., 
atropine) for subsequent treatments.  
Study procedures during treatment include physical examination and vital signs, CBC (with 
differential and platelet count), routine serum chemistries, urinalysis, serum samples for 
 
ECG, anti-drug antibody response, concomitant medications, and adverse events. Starting with 
the initial dose of IMMU-132 or TPC, CT or MRI examinations are to be obtained every 6 weeks 
for 36 weeks, then every 9 weeks thereafter, until the occurrence of progression of disease 
requiring discontinuation of further treatment. Responses identified prior to 36 weeks on study 
require confirmatory scans, which will be performed at the next scheduled scanning time-point 
(6 weeks later). For responses after 36 weeks, confirmatory scans will be done within 6 weeks of 
the scan showing the onset of response.  For each patient, the same imaging technique should be 
used throughout for tumor assessment.  The decision to discontinue the patient for tumor 
progression will be made by the investigator based on local imaging scan results.  Patients on 
either treatment arm who have progression of disease assessed for the first time during the study 
but who, in the opinion of the treating physician are deriving continued clinical benefit from 
IMMU-132 or TPC treatment, relative to other available treatment options, may continue to 
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be treated based on physician discretion as long as they continue to meet eligibility criteria. 
Clinical progression leading to patient discontinuation should be documented also by imaging 
scan of target lesions if possible. Patients who discontinue for other reasons than PD should a 
MRI/CT scan performed within 4 weeks from study treatment discontinuation so that 
documentation can be reviewed by the IRC. Patients who discontinue treatment due to toxicity 
will continue with radiologic response assessments according to the protocol-required schedule, 
until progression of disease or initiation of new therapy.  Additional CT or MRI may be 
performed at the discretion of the physician to assess disease status as medically indicated.  
Quality of life questionnaires will need to be completed at baseline, the beginning of every cycle, 
and at the final study visit. 
Within four weeks after discontinuing treatment, the patient will undergo an end-of-study 
evaluation.  All patients, including those prematurely terminating study participation, will be 
followed every 4 weeks for survival follow-up. This may be by telephone and will include 
documentation of any further anti-cancer therapy they may receive. Survival status may be also 
documented from public databases (e.g., Social Security database), as allowed by local 
regulations.  
3.2. 
Data Safety Monitoring Committee (DSMC) 
An independent DSMC will be convened at regular intervals to assess the progress of this study, 
and review safety and progression data, per an adopted DSMC charter.  In the absence of 
unexpected safety concerns, , the study will continue. 
4. 
PATIENT POPULATION 
The study population comprises previously-treated patients with relapsed/refractory metastatic 
TNBC.  Eligible patients must satisfy the following entry criteria at time of randomization: 
4.1. 
Inclusion Criteria 
1. Female or male patients, >18 years of age, able to understand and give written informed 
consent.   
2. Histologically or cytologically confirmed TNBC per ASCO/CAP criteria, based on the 
most recent analyzed biopsy or other pathology specimen. Triple negative is defined as  
<1% expression for estrogen receptor (ER) and progesterone receptor (PR) and negative 
for human epidermal growth factor receptor 2 (HER2) by in-situ hybridization.   
3. Metastatic disease documented by CT or MRI imaging.  
4. Measurable disease by CT or MRI as per RECIST 1.1. Bone-only disease is not 
permitted.  
5. Brain MRI must be done for patients with brain metastasis and patient must have 
had stable* CNS disease for at least 4 weeks.*  A maximum of 15% (N=74) of patients 
with brain metastases will be included in this trial. 
*“Stable” brain mets may be defined as:  
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 Prior local treatment by radiation, surgery, or stereotactic surgery 
 Imaging – stable or decreasing size after such local treatment   
 Clinically stable signs and symptoms 
 ≥2 weeks from discontinuation of anti-seizure medication. 
Corticosteroid (if needed) - dose should be stable, or decreasing for at least 2 weeks before 
randomization.   Steroid dose should be 20 mg or less of prednisone/prednisolone daily, or 
equivalent of a different steroid. 
6. At least 2 weeks beyond high dose systemic corticosteroids (however, low dose 
corticosteroids ≤ 20 mg prednisone or equivalent daily are permitted provided the dose is 
stable for 4 weeks).  
7. Refractory to or relapsed after at least two prior standard of care chemotherapy  regimens 
for unresectable, locally advanced or metastatic breast cancer (Appendix 1).  (These 
regimens will qualify regardless of triple-negative status at the time they were given. 
There is no cap on the number of prior chemotherapies for locally advanced or metastatic 
disease and earlier adjuvant or neoadjuvant therapy for more limited disease will qualify 
as one of the required prior regimens if the development of unresectable, locally 
advanced or metastatic disease occurred within a 12-month period of time after 
completion of chemotherapy).  
a.  For patients with a documented  germ-line BRCA1/BRCA2 mutation who received 
an approved PARP inhibitor,  the PARP inhibitor can be used to meet the criteria for 
one of two prior standard of care chemotherapies.  
b. All patients must have been previously treated with a taxane regardless of disease 
stage (adjuvant, neoadjuvant or advanced) when it was given. Patients who have 
contra-indications or are intolerant to taxanes are eligible provided that they received 
at least one cycle of a taxane and showed contra-indications or intolerance  during or 
at the end of that cycle. 
8. Eligible for one of the chemotherapy options listed as TPC (Eribulin, capecitabine, 
gemcitabine, or vinorelbine) as per investigator assessment.   
9. ECOG performance score of 0 or 1 (Appendix 2). 
10. Adequate hematology without transfusional support (hemoglobin > 9 g/dL, ANC > 1,500 
per mm3, platelets > 100,000 per mm3).  Blood transfusion or growth factor support is not 
allowed within 14 days prior to screening labs. 
11. Adequate renal and hepatic function (creatinine clearance of > 60 ml/min, may be 
calculated using Cockcroft-Gault equation; bilirubin ≤ 1.5 IULN, AST and ALT ≤ 2.5 x 
IULN or ≤ 5 x IULN if known liver metastases and serum albumin ≥3 g/dL).   
12. Recovered from all toxicities to Grade 1 or less by NCI CTCAE v4.03 (except alopecia 
or peripheral neuropathy that may be Grade 2 or less) at the time of randomization. 
Patients with Grade 2 neuropathy are eligible but may not receive vinorelbine as TPC. 
13. Patients must have completed all prior cancer treatments at least 2 weeks* prior to 
randomization including chemotherapy (includes also endrocrine treatment), radiotherapy 
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and major surgery.  *Prior antibody treatment for cancer must have been completed at 
least 3 weeks prior to randomization. 
14. Prior investigational agents are permitted, provided completion according to the 
timeframes above.   
15. Patients must have a life expectancy of 3-months or  greater,  in  the  opinion  of  the 
investigator. 
4.2. 
Exclusion Criteria 
1. Women who are pregnant or lactating.   
2. Women of childbearing potential or fertile men unwilling to use highly effective* 
contraception during study and up to three months  after treatment discontinuation in 
women of child-bearing potential and six months in males post last study drug.    
3. Patients with Gilbert’s disease. 
4. Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, 
while patients with other prior malignancies must have had at least a  
3-year disease-free interval.  
5. Patients known to be HIV positive,  
6. Patients with hepatitis B positive, or hepatitis C positive infection**.  
7. Known history of unstable angina, MI, or CHF present within 6 months of randomization 
or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring 
anti-arrhythmia therapy. 
8. Known history of clinically significant active COPD, or other moderate-to-severe chronic 
respiratory illness present within 6 months of randomization. 
9. Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation 
within 6 months of randomization. 
10. Infection requiring antibiotic use within one week of randomization. 
11. Patients with active chronic inflammatory bowel disease (ulcerative colitis, Crohn 
disease) and patients with a history of bowel obstruction 
12. Patients who have received a live vaccine within 30 days of randomization 
13. Patients who previously received irinotecan. 
14. Rapid deterioration during screening prior to randomization, e.g. significant change in 
performance status,  20% decrease in serum albumin levels, unstable pain symptoms 
requiring modifications in analgesic management. 
15. Other concurrent medical or psychiatric conditions that, in the Investigator’s opinion, 
may be likely to confound study interpretation or prevent completion of study procedures 
and follow-up examinations. 
*Highly effective is defined as i.e. Combined (estrogen and progestogen containing) 
hormonal contraception: oral, intravaginal, transdermal, progestin -only hormonal 
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contraception associated with inhibition of ovulation: oral, injectable, implantable, 
intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal 
occlusion, vasectomized partner, sexual abstinence). Abstinence refers to 
‘True abstinence’ which means it is in line with the preferred and 
usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptotherma, 
post-ovulation methods), declaration of abstinence for the duration of exposure to study 
treatment, and withdrawal are not acceptable methods of contraception. 
** In patients with a history of HBV, hepatitis B core antibody (HBcAb) testing is required and 
if positive, then HB DNA testing will be performed and if positive the patient will be excluded. 
4.3. 
Concomitant Medications and Procedures 
 No anti-cancer therapies, aside the study drug (IMMU-132)/TPC are permitted during 
this study.  However, palliative and/or supportive medications, such as bone-
modifying medications (bisphosphonates or denosumab), and/or procedures such as 
radiation and surgery will be allowed at the investigator’s discretion. If a patient 
requires palliative radiotherapy for brain metastases, IMMU-132 or TPC should be 
interrupted one week before the procedure and reinstated two weeks after the 
procedure, provided that palliative radiotherapy is not indicated for tumor 
progression, in which case the patient will have to be discontinued for the trial. 
 Premedication for prevention of infusion reaction with antipyretics, H1 and H2 
blockers are strongly recommended before sacituzumab govitecan infusions. 
Corticosteroids (50 mg hydrocortisone or equivalent P.O. or I.V.) may be added if 
necessary and were used in approximately two-thirds of patients from the phase 2 
trial. Premedication according to established guidelines with a two or three drug 
combination regimen (e.g. dexamethasone with either a 5-HT3 receptor antagonist or 
a NK1 receptor antagonist, as well as other drugs as indicated) for prevention and 
treatment of chemotherapy-induced nausea and vomiting (CINV) is strongly 
recommended (see below for information on medication affecting QT interval).   
 Additional antiemetics, sedatives, and other supportive measures may also be 
employed as clinically indicated.  In addition, all patients should be given 
medications for use at home for prevention and treatment of nausea, vomiting and 
diarrhea.   Patients should be instructed as to how to aggressively treat nausea and 
vomiting with these out-patient medications.  
 At the onset of diarrhea, promptly initiate loperamide, 4 mg initially followed by 2 
mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue 
loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g. 
fluid and electrolyte substitution) may also be employed as clinically indicated.  All 
patients should be given take-home medications with clear instructions for treatment 
of diarrhea.  
 Patients who exhibit an excessive cholinergic response to sacituzumab govitecan 
treatment (e.g., abdominal cramping, diarrhea, salivation, etc.) can receive 
appropriate premedication (e.g., atropine) for subsequent treatments. 
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 Patients receiving IMMU-132 who experience neutropenia will be prescribed growth 
factors as per Section 6.4.6 as clinically indicated, including prophylactically. Other 
hematopoietic growth factors or blood transfusions are allowed at physician’s 
discretion. Patients on TPC may receive G-CSF, other hematopoietic growth factors 
or blood transfusions per physician discretion. 
 High dose systemic corticosteroids are not allowed within 2 weeks of randomization.  
Low dose, stable doses of corticosteroids ≤ 20 mg prednisone or equivalent daily are 
permitted if patient entered the study on low dose steroids for their treated brain 
metastasis, or if medically indicated as part of their premedications for infusions.   
(topical steroids and corticosteroid inhalers are allowed). 
 Antiemetics, anti-diarrheal medications, cytokines or blood transfusions should be 
administered as clinically necessary. 
 Other supportive and palliative care is allowed as medically warranted. 
CYP3A4 inducers and inhibitors 
There is a potential for altered toxicity profile from common medications and foods with 
possible potent effects on liver metabolism of drugs, such as irinotecan and SN-38.  As such, all 
patients should be advised to avoid the following medications while on study:  
CYP 3A4 Inhibitors 
CYP 3A4 Inducers 
 
Amiodarone 
Amprenavir 
Aprepitant 
Atazanavir 
Chloramphenicol 
Clarithromycin 
Conivaptan 
Cyclosporine 
Darunavir 
Dasatinib 
Delavirdine 
Diltiazem 
Erythromycin 
Fluconazole 
Fluoxetine 
Fluvoxamine 
Fosamprenavir 
Grapefruit juice 
Imatinib 
Indinavir 
Isoniazid 
Itraconazole 
Ketoconazole 
Lapatinib 
Miconazole 
Nefazodone 
Nelfinavir 
Posaconazole 
Ritonavir 
Quinupristin 
Saquinavir 
Tamoxifen 
Telithromycin 
Troleandomycin 
Verapamil 
Voriconazole 
Aminoglutethimide 
Bexarotene 
Bosentan 
Carbamazepine 
EfavirenzFosphenytoin 
Griseofulvin 
Modafinil 
Nafcillin 
Nevirapine 
Oxcarbazepine 
Phenobarbital 
Phenytoin 
Primidone 
Rifabutin 
Rifampin 
Rifapentine 
St. John's wort 
4.4. 
Patients receiving anticoagulants 
As irinotecan and SN-38 may affect CYP2C9, patients receiving Coumadin or warfarin may be 
at risk and those patients should be more intensively monitored for their Coumadin/warfarin 
during study treatment.  
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4.5. 
Patients receiving QT prolonging drugs  
Patients receiving QT prolonging drugs should be carefully monitored as some of the study 
medications may further increase the QT interval. When possible, the investigator should 
consider avoiding the following medications and using alternative medications that do not affect 
the QT interval.    While  5-HT3  receptor antagonist compounds can prolong the QT interval, 
they have been found to be effective in treatment/prophylaxis of nausea associated with 
sacituzumab govitecan and investigators are advised to monitor patients closely when used.   
Medications affecting QT interval 
Amantadine 
Amiodarone 
Azithromycon 
Chloroquine 
Chlorpromazine 
Cisapride 
Clarithromycin 
Clozapine 
Disopyramide 
Dofetilide 
Dolasteron 
Domperidone 
Erythromycin 
Escitalopram 
Granisetron 
Haloperidol 
Lapatinib 
Lithium 
Methadone 
Moxifloxacin 
Nilotinib 
Ondansetron 
Pentamidine 
Procainamide 
Quetiapine 
Quinidine 
Resperidone 
Roxithromycin 
Sertinodole 
Sotalol 
Tamoxifen 
Telithromycin 
Terfaenadine 
Venlaxafine 
Zisprasidone 
Guidance for Industry, E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for 
Non-Antiarrhythmic Drugs. U.S. Department of Health and Human Services, Food and Drug Administration, Center 
for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER) October 2005, 
ICH.  
Geoffrey K Isbister and Colin B Page. Drug induced QT prolongation: the measurement and assessment of the QT 
interval in clinical practice. Br J Clin Pharmacol. 2013 Jul; 76(1): 48–57.  
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5. 
STUDY PROCEDURES 
Unless otherwise specified, collection windows for study time points are within ± 2 days for the 
treatment schedule and ± 5 business days for response assessments. Planned deviations in 
treatment schedule are allowable up to 7 days due to holidays, vacation or personal reasons. 
 
 
Serum and whole blood samples obtained for anti-drug antibodies, 
 and 
UGT1A1 levels are to be shipped to the Sponsor’s designee who will perform these assays.  
Instructions for shipping these blood samples are given in Appendix 3.  Otherwise, all 
procedures are to be performed locally at each study site.  
5.1. 
Informed Consent 
No study-specific procedure or alteration of patient care will be undertaken until informed 
consent has been obtained from the patient or legal representative.  The Investigator will explain 
the nature and scope of the study, potential risks and benefits of participation, and answer 
questions for the patient and/or legally authorized representative.   
A table of approved or standard therapeutic regimens is included in Appendix 1.  Patients must 
be informed that alternatives to receiving IMMU-132 are available prior to consenting to 
participate in this trial. 
If the patient agrees to participate, the informed consent form must be signed, dated, and 
witnessed, with a copy given to the subject. 
5.2. 
Patient Registration 
At such time as a patient has been deemed eligible for the study and all required screening 
evaluations have been completed the patient can be randomized.  This will be done via an 
interactive web-based response system.  
Randomization must occur on or before Cycle 1 Day 1, such that dosing commences within 5 
days after randomization.  
5.3. 
Pre-Study/Baseline Evaluations (see Study Calendar, Appendix 4) 
Baseline and screening evaluations conducted to establish eligibility will be performed within 28 
days prior to first study treatment: 
 Signed informed consent 
 Urine or serum HCG, in women of childbearing potential (required within 7 days 
prior to treatment) 
 Histology review to confirm TNBC diagnosis 
 BRCA 1&2 mutational status, if known 
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 Medical/surgical history review with treatment history to include treatment response 
and also time to progression for last therapy regimen 
 ECOG Performance evaluation 
 Prior/Concomitant medications review 
 Physical examination with vital signs, defined as heart rate, blood pressure, 
respiratory rate, body weight and body temperature 
 Standard 12-lead electrocardiogram (ECG) 
 CBC including platelet count, with WBC differential in absolute cell counts, to be 
repeated within 72 hours of cycle 1, day 1 to confirm eligibility 
 Routine serum chemistries (glucose, creatinine, BUN, total bilirubin, AST, ALT, 
LDH, alkaline phosphatase, serum albumin, total protein, Na, K, calcium, Cl, CO2, 
magnesium and phosphorus) 
 Hepatitis B surface antigen test, hepatitis C antibody test. 
 Creatinine clearance (may be calculated using Cockcroft-Gault equation) 
 Baseline serum sample prior to receiving sacituzumab govitecan for anti-drug 
antibody (hRS7 and SN-38) response (frozen, to be shipped to Sponsor’s designee for 
analysis) 
 Urinalysis 
 CT or MRI with contrast as appropriate (chest, abdomen, pelvis, other regions of 
known/suspected involvement)*  
 Brain MRI in patients with known brain metastases 
 Quality of life patient questionnaire (EORTC QLQ C30) 
 
 
 
  
 A single whole-blood sample to be collected from each patient prior to receiving 
IMMU-132, for determination of UGT1A1 genotype 
 
*CT and MRI of the chest, abdomen and pelvis (CAP) must be of diagnostic quality and include 
appropriate use of contrast for the region being imaged.  
5.4. 
Procedures During Treatment (see Study Calendar, Appendix 4) 
 Dosing (IMMU-132 dosing is based on patient’s body weight on Day 1 of each cycle 
(or at each dosing day if change in body weight is >10% or if required by 
institutional policy. TPC dosing is based upon body surface area as per local 
standard of care.)  
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 Vital signs*  (For IMMU-132, prior to first infusion and every 15 minutes for the first 
hour then every 30 minutes until completing IV administration, at completion, and 30 
minutes post infusion). In absence of significant changes, may be reduced with 
subsequent doses to prior to infusion, at 30 minutes, and then at completion. For TPC, at 
least before, once during and after IV administration and once at study visits for oral 
treatment; otherwise as per local standard of care). *heart rate, systolic and diastolic 
blood pressure, respiratory rate, and body temperature.  Timepoints can be ± 1-2 min. 
 Blood samples prior to infusion: 
 CBC (with differential in absolute cell counts and including platelet count). For 
IMMU-132 or TPC given intravenously (eribulin, gemcitabine, vinorelbine), 
required every treatment day.  For TPC given orally (capecitabine), required at 
start of each cycle and on other treatment days and study visits as per local 
standard of care. In event of ≥ Grade 3 hematologic toxicity, to be obtained more 
frequently at the discretion of the managing physician until recovery to ≤ Grade 2 
levels. 
 Serum chemistry panel (glucose, creatinine, BUN, total bilirubin, AST, ALT, 
LDH, alkaline phosphatase, serum albumin, total protein, Na, K, calcium, Cl, 
CO2, magnesium and phosphorus). For IMMU-132 or TPC given intravenously 
(eribulin, gemcitabine, vinorelbine), required every treatment day.  For TPC 
given orally (capecitabine), required at start of each cycle and on other treatment 
days and study visits as per local standard of care. To be obtained more 
frequently at the discretion of the managing physician if abnormal results warrant 
follow-up. 
 Urinalysis, pregnancy test (if applicable), and ECG.  For IMMU-132, required only 
on Day 1 of even cycles (cycle 2, 4, 6, 8, etc.). For TPC, required at the start of even 
cycles (every 6 weeks if given weekly [e.g. vinorelbine]). For patients receiving 
Gemcitabine, pregnancy test will be performed at the start of every cycle (every 4 
weeks). 
 Physical examination. Required on Day 1 of all cycles for IMMU-132 and at start of 
each cycle for TPC (every 3 weeks if given weekly [e.g. vinorelbine]) 
 Adverse event reporting, all patients at every study visit 
 Concomitant medications (continued, changed), all patients at every study visit 
 Serum samples for Exposure-Response (For IMMU-132, required on both Days 1 
and 8 of  Cycle 1 only, prior to infusion and 30 minutes afterwards; frozen 
immediately, to be shipped to Sponsor’s designee for analysis; For TPC, not 
applicable) 
 Anti-drug antibody sample (frozen immediately, to be shipped to Sponsor’s designee 
for analysis) [For IMMU-132, required Day 1 of even cycles. For TPC, not 
applicable] 
CT or MRI examinations.  Starting with the initial dose of IMMU-132 or TPC, CT or MRI 
scans are to be obtained in all patients after the first treatment dose every 6 weeks for 36 weeks, 
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then every 9 weeks thereafter until the occurrence of progression of disease requiring 
discontinuation of further treatment. Patients on either treatment arm who have progression of 
disease assessed for the first time during the study but, who, in the opinion of the treating 
physician are deriving continued clinical benefit from IMMU-132 or TPC treatment, relative to 
other available treatment options, may continue to be treated. Patients who discontinue 
treatment due to toxicity will continue with radiologic response assessments at the protocol-
required schedule, until progression of disease or initiation of new therapy.  CT or MRI imaging 
will include chest, abdomen, pelvis, other areas of known/suspected involvement, with contrast 
as appropriate. Patients with known brain metastasis must have a brain MRI. Target and non-
target lesions must be determined by the clinical site at time of randomization. Responses 
identified prior to 36 weeks on study require confirmatory scans, which will be performed at the 
next scheduled scanning time-point (6 weeks later). For responses after 36 weeks, confirmatory 
scans will be done within 6 weeks of scan showing the onset of response. For each patient, the 
same imaging technique should be used throughout for tumor assessment.  Clinical progression 
leading to patient discontinuation should be documented also by CT or MRI scan of target 
lesions if possible. Patients who discontinue treatment for other reasons than PD should a 
MRI/CT scan performed within 4 weeks from study treatment discontinuation so that 
documentation can be reviewed by the IRC. Additional CT or MRI studies may be performed at 
the discretion of the physician to assess disease status as medically indicated. 
Note: A qualifying CT or MRI scan of the chest, abdomen, or pelvis must be of diagnostic 
quality, including use of appropriate contrast for the region being imaged.  
Quality of life questionnaires (EORTC QLQ-C30; see Appendix 5) will need to be completed 
in all patients at baseline, at Day 1 of each cycle, and at the final study visit. 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
  
 
 
 
 
 
 
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5.6. 
Final Study Evaluation or Unscheduled/Early Termination Visit 
To be conducted within 4 weeks after the last dose of IMMU-132 or TPC or in the event of 
premature study termination: 
 Physical examination (complete) 
 Pregnancy test, if applicable 
 Vital signs defined  as heart rate, systolic and diastolic blood pressure, respiratory rate, 
body weight and body temperature.  
 CT or MRI with contrast as appropriate (chest, abdomen, pelvis, other regions of 
known/suspected involvement)*  
 Blood samples  
 CBC (with differential and platelet count)  
 Serum chemistry panel 
 Serum sample for anti-drug antibodies (In patients receiving IMMU-132 only, 
frozen immediately, to be shipped to Sponsor’s designee for analysis)  
 Urinalysis 
 ECG 
 Concomitant medications (continued, changed) 
 Adverse event reporting 
 Quality of Life (EORTC QLQ-C30)  
*CT and MRI of the chest, abdomen and pelvis (CAP) must be of diagnostic quality and 
include appropriate use of contrast for the region being imaged.  
5.7. 
Long-Term Follow-Up 
All patients will be followed every 4 weeks thereafter for survival, which may be by telephone 
and will include documentation of any further therapy administrated for their breast cancer. 
5.8. 
Criteria for Removal from Protocol Treatment 
Patients may be removed from protocol treatment under the following conditions: 
 First documentation of progressive disease or symptomatic deterioration indicating 
treatment failure in the absence of clinical benefit. 
 Unacceptable toxicity 
 Treatment delay for any reason >3 weeks 
 Pregnancy 
 Physician decision (non-compliance of the patient (to treatment or protocol-specified 
procedures), or continuing treatment not in the best interests of the patient) 
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 Withdrawal of consent at any time for any reason 
Patients will end the study under any of the following conditions: 
 Death 
 Withdrawal of consent for the study at any time for any reason 
 Lost to follow-up 
 Sponsor decision 
5.9. 
End of Study 
End of study is defined as the point in time when the number of progression events required for 
the primary analysis have been reached or if the Sponsor terminates the study, whichever comes 
first.  The primary analysis is expected to occur minimally 9 months after the last patient is 
randomized to the study. Survival data may continue to be collected after End of Study.  
At the completion of the trial, subjects who are deriving benefit from sacituzumab govitecan may 
continue to receive treatment in a rollover study, if one is available. This rollover study may be 
designed to provide continued access to sacituzumab govitecan for eligible subjects who have 
previously participated in Immunomedics sponsored parent study, who are tolerating 
sacituzumab govitecan, have no evidence of progressive disease or are still deriving clinical 
benefit despite progression (as assessed by the investigator). Subjects will receive the dose of 
sacituzumab govitecan currently receiving in the parent study at the time of consenting to 
participate in the rollover study, if applicable. 
6. 
STUDY DRUG INFORMATION 
6.1. 
Description of Study Drug 
hRS7 is a CDR-grafted, humanized monoclonal IgG1 anti-Trop-2 antibody.  The antibody is 
prepared using cell culture methods in accordance with Food and Drug Administration (FDA) 
guidelines for the manufacture and testing of monoclonal antibody products for human use.  SN-
38 (7-ethyl-10-hydroxy-camptothecin) is a small molecule and the active metabolite of the 
chemotherapeutic agent, irinotecan.  
IMMU-132 is an antibody drug-conjugate prepared by Immunomedics, Inc. (Morris Plains, NJ).  
The conjugation uses a spacer containing a cleavable-carbonate bond to attach SN-38 to reactive 
cysteine thiols present on the hRS7 antibody.  For clinical use, 10 mg/mL IMMU-132 is 
formulated in 25 mM MES, pH 6.5, together with the other excipients (25 mM trehalose, 0.01% 
Polysorbate 80), which is then lyophilized.  Glass vials containing 200 mg of IMMU-132 as a 
sterile, non-pyrogenic, lyophilized powder are to be stored under refrigerated conditions (2-8ºC) 
until used.  Each vial is labeled “For Investigational Use Only” and identified by study drug 
name, lot number, and dose.  Since the formulated drug product contains no preservative, vials 
should be used only once.  
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6.2. 
Drug Accountability 
All vials of study drug must be stored under refrigeration (monitored at 2-8oC) in a locked room 
that can be accessed only by the pharmacist, the study Investigator, or another duly authorized 
study/site personnel.  The study medications must not be used outside of the context of this 
protocol.  Under no circumstances should the Investigator or other site personnel supply study 
drug to other Investigators, patients, or clinics, or allow supplies to be used other than as directed 
by this protocol without prior written authorization from Immunomedics, Inc. 
Adequate records documenting receipt, use, return, loss, or other disposition of study drug vials 
must be kept.  A complete drug accountability record, supplied by Immunomedics (or its 
designee or NCI drug accountability forms), or computer records used by the pharmacy at the 
investigational site, can be used to provide drug accountability.  In all cases, information 
describing study medication supplies and their disposition, patient-by-patient, must be provided 
and signed by the Investigator (or the pharmacist or other person who dispensed the drug) and 
collected by the Study Monitor.  Requisite data include relevant dates, quantities, batches or code 
numbers, and patient identification for patients who received trial product. 
At the end of the study, following authorization by study management, study medication may be 
destroyed at the site as dictated by the appropriate standard operating procedures at the 
participating institutions.  Destruction must be documented with signature by institution’s 
pharmacist or delegate.  Alternatively, after notification, all unused products will be collected by 
the Study Monitor and returned to Immunomedics, Inc., or designee. 
6.3. 
Study Drug Preparation 
Please use Pharmacy Binder as primary source for study drug preparation.  
Table 3: 
IMMU-132 Preparation for 10 mg/kg Dosing (Assumes 70-kg Patient) 
Total Dose Needed  
700 mg 
(200 mg/vial) 
a.      Vials Required  
4 
b.   Volume of saline to be used for reconstitution 
20 mL 
c.      Volume after reconstitution of each vial with USP saline 
80 mL 
d.      Volume Withdrawn for Scheduled Dose 
70 mL 
e.      Dilute with Normal Saline 
180 mL 
f.      Total Volume Dispensed   
250 mL 
g.       Final Concentration (mg/mL) 
2.8 
 
6.4. 
IMMU-132 Treatment 
Note: This section specifically provides guidance for IMMU-132 administration and toxicity 
management, including guidelines for infusion reactions, dose delay, dose reduction and 
treatment discontinuation. For similar information regarding the 4 TPCs in this study, please see 
Section 6.5. 
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6.4.1. 
Preventative Medications 
Premedication for prevention of infusion reaction with antipyrectis, H1 and H2 blockers should be 
administered before sacituzumab govitecan infusions. Corticosteroids (hydrocortisone 50 mg or 
equivalent P.O. or I.V.) may be added if necessary and were used in approximately two-thirds of 
the patients in the Phase 2 trial.  Premedication according to established guidelines with a two or 
three drug combination regimen (e.g. dexamethasone with either a 5-HT3 receptor antagonist or 
a NK1 receptor antagonist, as well as other drugs as indicated) for prevention and treatment 
of chemotherapy-induced nausea and vomiting (CINV) is strongly recommended.  Additional 
antiemetics, sedatives, and other supportive measures may also be employed as indicated per 
investigator discretion.  All patients should be given medications to take home for prevention 
and treatment of nausea and vomiting.  At the onset of diarrhea, promptly initiate loperamide, 4 
mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. 
Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g. 
fluid and electrolyte substitution) may also be employed as clinically indicated.  All patients 
should be given take-home medications with clear instructions for treatment of diarrhea.  Patients 
who exhibit an excessive cholinergic response to treatment with sacituzumab govitecan (e.g., 
abdominal cramping, diarrhea, salivation, etc.) can receive appropriate premedication (e.g., 
atropine) for subsequent treatments. 
6.4.2. 
Vital Signs 
Vital signs (heart rate, systolic and diastolic blood pressure, respiratory rate, and body 
temperature) 
for IMMU-132 will be assessed prior to the first infusion of cycle 1 and every 15 ± 5 minutes for 
the first hour and then every 30 minutes until completing IV administration, at completion, and 
then 30 minutes post infusion. In absence of significant changes, may be reduced with 
subsequent doses to prior to infusion, at 30 minutes, and then at completion. Timepoints can be ± 
1-2 min.  
6.4.3. 
Intravenous Administration of IMMU-132 
Do not administer as an IV push or bolus.  IMMU-132 is administered intravenously as a slow 
infusion as described below.  
Intravenous access must be well established prior to initiating infusion.  At the time of dosing, 
the IV line will be connected to an infusion container containing the prepared volume of IMMU-
132.  Either gravity or an infusion pump may be used.  Only normal saline should be used as the 
infusion base solution, since the Sponsor has not examined the compatibility of IMMU-132 with 
other infusion diluents. 
The initial infusion should proceed slowly.  If vital signs remain stable and in the absence of 
infusion reactions, the infusion rate can be incrementally advanced following suggested 
guidelines given in Table 4, and following completion, the intravenous line should be flushed 
slowly with 20 mL normal saline and the end of infusion time recorded.  In the event of infusion 
reactions or vital sign changes, the infusion rate may be slowed, interrupted or terminated, as 
considered appropriate by the managing physician (See Section 6.4.4). 
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Table 4: 
Infusion Rate Guidelines For Patients Remaining Stable in Absence of 
Hypersensitivity or Infusion-Related Events 
Infusion Rate 
Infusion #1 
Subsequent Infusions  
Initial Rate (first 15 min.) 
50 mg/hr, or less 
100 - 200 mg/hr 
Incremental Rate (advance every 15-30 min.)  
50 mg/hr 
100 - 200 mg/hr 
Maximum Recommended Rate  
500 mg/hr 
1000 mg/hr 
 
6.4.4. 
Managing IMMU-132 Infusion Toxicity 
The Sponsor’s designee should be notified within 24 hours in the event of any serious infusion 
reaction occurring with IMMU-132 or one of the TPC drugs. 
NCI CTCAE version 4.03 is used to grade all adverse events and to provide management 
guidelines for infusion toxicity.   
For a serious infusion reaction considered severe or life threatening (NCI toxicity Grade 3 or 
higher) the infusion must be permanently terminated. 
 Examples of such events include: serious or clinically significant cardiopulmonary 
events, severe allergic (symptomatic bronchospasm) or anaphylactic reactions, or 
other severe reactions.   
 The occurrence of Grade 3 infusion-related reactions (e.g., prolonged infusion related 
reactions not rapidly responsive to symptomatic medication and/or brief interruption 
of infusion) also require the infusion to be permanently terminated. 
Otherwise, for moderate infusion toxicity (Grade 2 events), the infusion should be temporarily 
stopped for at least 15 minutes or until symptoms resolve, and then resumed at the slowed 
infusion rate, if the patient is stable. Recommended actions for mild toxicity (Grade 1 events) 
include slowing the remaining infusion rate. Any infusion toxicity must have resolved to ≤ Grade 
1 prior to a patient receiving the next scheduled infusion. 
Additional Medications 
Patients may be medicated during treatment as indicated in the judgment of the treating 
physician to control potential infusion or hypersensitivity responses.  For anaphylactic reactions, 
appropriate medical measures (e.g., epinephrine, antihistamines, hydrocortisone, and IV fluids) 
should be taken.  Such a subject should not receive additional study drug and should be 
discontinued from the study.  
Nausea, Vomiting and Diarrhea 
Gastrointestinal toxicity may be dose-limiting with IMMU-132. Premedication according to 
established guidelines with a two or three drug combination regimen (e.g. dexamethasone with 
either a 5-HT3 receptor antagonist or a NK1 receptor antagonist, as well as other drugs as 
indicated)for prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) is 
recommended.  
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At the onset of diaiThea, promptly initiate loperamide, 4 mg initially followed by 2 mg with 
every episode of diai-rhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after 
diaiThea resolves. Additional supportive measures (e.g. fluid and electrolyte substitution) may 
also be employed as clinically indicated. All patients should be given take-home medications 
with cleai· instructions for ti·eatment of dianhea. 
Additional antiemetics, sedatives, and other suppo1iive measures may also be employed as 
clinically indicated. All patients should be given take home medications for prevention and 
ti·eatment of nausea, vomiting and diaIThea. Hospital or institutional guidelines may exist and 
should be consulted for recommended ti·eatment of these conditions in patients received cancer 
therapy. A paiiial list of the major medications is provided below in Table 5 but the 
hospital/institution guidelines or the references below should be consulted for more detailed 
infonnation as to management of these conditions. 
Patients who exhibit an excessive cholinergic response to IMMU-132 ti·eatment (e.g., abdominal 
cramping, diaiThea, salivation, etc.) can receive appropriate premedication (e.g., ati·opine) for 
subsequent treatments. 
Chemothernpy Induced Nausea Vomiting (CINV) guidelines 
Hi2:h 1·isk 
Not applicable 
Moderate risk 
IMMU-132 
Low lisk 
Vinorelbine, eribulin, gemcitabine, capecitabine 
Minimal 1·isk 
Not applicable 
Sue:e:ested anti-emetic re2imen 
Anti-emetic re2imen 
Delaved CINV 
Anti-emetic re2imen 
High 1·isk 
5HT3 antagonist+ 
High risk 
Dexamethasone ( days 2-4) + 
dexamethasone+ aprepitant 
Aprepitant (days 2-3) + lorazepam in 
selected patients 
Moderate risk 
5HT3 antagonist+ 
Moderate risk 
Dexamethasone ( days 2-4) + aprepitant 
dexamethasone+ aprepitant 
day 2-3 (ifused on day 1) + lorazepam 
in selected cases 
in selected patients 
Low lisk 
Dexamethasone or 
Low risk 
No anti-emetics 
metoclopramide or 
prochlorperazine 
Minimal 1·isk 
No anti-emetics 
Minimal risk 
No anti-emetics 
Table 5: 
Recommended Medications for Nausea, Vomiting and Diarrhea* 
Agent 
Dose/Frequency 
Route of 
administration 
For Prevention of Acute Emesis: 
Palonosetron 
0.075mg 
Decadron 
10-20 mg 
PO or IV 
10 mg eve1y 12 hours 
PO or IV 
Granisetron 
1 mg or 0.01 mg/kg 
IV 
1-2 mg daily 
PO 
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Table 5: 
Recommended Medications for Nausea, Vomiting and Diarrhea* 
Agent 
Dose/Frequency 
Route of 
administration 
Ondansetron 
8 mg or 0.15 mg/kg 
IV 
16-24 mg daily 
PO 
Lorazepam 
0.5-2 mg eve1y 4-6 hours 
PO or sublingual 
Alprazolam 
0.5-2 mg eve1y 4-6 hours 
PO or sublingual 
For Delayed Emesis: 
Fosaprepitant 
150 mg day 1 only 
IV 
For Diarrhea: 
4 mg initially followed by 2 mg with eve1y episode 
Loperamide 
for a maximum of 16 mg daily. Discontinue 12 PO 
hours after dianhea resolves and normal diet is 
resumed. 
Octreotide 
100-150 mcg three times daily 
Subcutaneously 
Fluoroquinolones 
(for (e.g., ciprotloxacin 250-750 mg eve1y 12 hours for 
dianhea persisting > 24 7 days) 
PO 
hrs, ANC < 500 or fever 
with dianhea) 
* Based on Benson 2004; Kris 2006. 
6.4.5. 
IMMU-132 Dosing Schedule 
All patients receive IMMU-132 to be administered weekly for 2 consecutive weeks (2 weekly 
doses plus 1 week without treatment represents a single 3-week cycle). Treatment cycles can be 
continued without a rest period in the absence of progression of disease or unacceptable toxicity. 
Patients on either treatment arm who have progression of disease assessed for the first time 
during the study but, who, in the opinion of the treating physician are deriving continued clinical 
benefit from IMMU-132 or TPC treatment, may continue to be treated. Planned deviations in 
treatment schedule are allowable up to 7 days due to holidays, vacations or personal reasons. 
6.4.6. 
IMMU-132 Dose Reduction and Termination Guidelines 
An overview of dose reduction and discontinuation is provided in the table below. The protocol 
allows aggressive medical management of patients in order to avoid dose reduction and dose 
delay as much as possible. Growth factors should be initiated according to guidelines in 
Section 6.4.6 and Table 6 and may be used prophylactically as clinically indicated. In patients 
who would be considered high risk for neutropenia (those who experienced febrile neutropenia 
or Grade 3-4 neutropenia with prior treatments), use of growth factors may be initiated early on 
and used prophylactically as early as cycle 1. 
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Table 6: 
IMMU-132 
Dose 
10 mg/kg IV on day 1 and 8 of a 21-day cycle 
When dose 
Infusion reaction 
Grade 2: stop for 15 min or until resolution then resume at a slower rate 
reduce 
Grade 1: slow infusion rate 
Any infusion reaction must have resolved to < grade 1 before the next scheduled infusion 
Hematologic 
If patient experience grade::::_ 2 neutropenia on cycle 1 day 1, treatment initiation should be withheld until~ Grade 1. If 
toxicicy-Use growth 
delay more than 3 weeks, discontinue 
factors at any time 
If patient experience Grade~ 3 neutropenia in subsequent treatment cycles, treatment initiation should be withheld 
as clinically 
until 5 grade I and growth factors should be used as clinically indicated. Patient will be assessed weekly for Grade 3 
indicated. including 
and bi-weekly for grade 4. If delay more than 3 weeks, discontinue 
QfOQhylactically 
In the event of neutropenia Grade 3 on the time of scheduled treatment day: 
Resume treatment without dose reduction if delay is 1 week only 
Resume treatment without dose reduction with addition of growth factors if delay is 2 or 3 weeks (as is also 
reconunended for delays greater than 1 week) 
Resume treatment with a dose reduction if patients is already receivingy;rowth factors 
Dose reduction scheme 
Grade 4 neutropenia 2, 7 days, Grade 3 febrile neutropenia 
First occurrence 
Add growth factors 
Second occurrence 
25% dose reduction 
Third occtmence 
50% dose reduction 
Fourth occmTence 
Discontinue 
GI toxicicy 
If patient experience Grade~ 2 GI toxicity on cvcle 1 day 1, treatment initiation should be withheld until 5 Grade 1. If 
delay more than 3 week, discontinue 
If patient experience Grade 
3 GI toxicity in subsequent treatment cvcles, treatment initiation should be withheld 
until~ Grade 1. Patient will be assessed weekly for grade 3 and bi-weekly for Grade 4. If delay more than 3 week, 
discontinue 
In the event of GI toxicity Grade_::::. 3 on the time of scheduled treatment day: 
Resume treatment without dose reduction if delay is 1 week only 
Resume treatment without dose reduction if delay is 2 or 3 week 
Non-hematologic 
Dose reduction scheme 
toxicity 
-Grade 4 non-hematological toxicity of any dmation 
First occurrence 
25 % reduction 
-Any Grade > 3 nausea, vomiting or diarrhea not controlled by 
antiemetics and antidiarrheal agents 
Second occurrence 
50 % reduction 
-Grade >3 non-hematologic toxicity > 48h despite optimal 
medical treatment 
Third occtmence 
discontinue 
-Grade 3 non-hematologic toxicity which delays dose by 2-3 
weeks for recovery to < grade I 
Discontinuation 
Grade 3-4 infusion reaction 
Any delay more than 3 weeks 
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The major toxicities of IMMU-132 are expected to be gastrointestinal symptoms and 
hematologic suppression.  All patients will be closely monitored over the course of their 
treatment and aggressively medically managed in order to prevent dose reductions and delays 
where possible, with NCI-CTCAE v4.03 used to grade all adverse events and to provide dose 
reduction, delay or cessation guidelines in the event of toxicity.  
If a patient experiences ≥ Grade 2 neutropenia or ≥ Grade 2 GI toxicity on the first treatment day 
(Cycle 1, Day 1), growth factors should be administered and treatment initiation should be 
withheld until resolved to ≤ Grade 1.  If recovery to ≤ Grade 1 requires more than three-week 
delay, the patient should be withdrawn from the study. In subsequent treatment cycles, if a 
patient experiences ≥ Grade 3 neutropenia or ≥ Grade 3 GI toxicity, the treatment should be 
withheld until resolved to ≤ Grade 1 and patients will be assessed at least weekly (biweekly for 
Grade 4 toxicities).  If recovery to ≤ Grade 1 requires more than a 3-week delay, the patient 
should come off the study.   
Treatment will be permanently discontinued for a patient in the event of any ≥ Grade 3 infusion 
reactions which occur after pre-medication with antihistamines, H2 blockers and steroids.  
In the event of ≥ Grade 3 treatment-related neutropenia at the time of a scheduled treatment day, 
the dose will be held and patients will be assessed at least weekly.  Growth factors should be 
initiated.  If recovery to ≤ Grade 1 delays the next dose by only one week, treatment may resume 
then without dose reduction with growth factor support as per Section 6.4.6 and Table 6.  If 
recovery to ≤ Grade 1 delays the next dose by 2 or 3 weeks, treatment may be resumed at the 
same dose with the addition of growth factors. If a patient is already receiving growth factors 
support and the next treatment is delayed by 2 or 3 weeks, treatment must be resumed at a 
reduced dose (Table 6).  If recovery to ≤ Grade 1 requires more than a three-week delay, 
treatment must be permanently discontinued.   
In the event of other ≥ Grade 3 treatment-related non-hematologic toxicity at the time of a 
scheduled treatment day, the dose will be held and patients will be assessed at least weekly.  If 
recovery to ≤ Grade 1 delays the next dose by only one week, treatment may resume then 
without dose reduction.  If recovery to ≤ Grade 1 delays the next dose by 2 or 3 weeks, treatment 
must be resumed at a reduced dose (Table 6).  If recovery to ≤ Grade 1 requires more than a 
three-week delay, treatment must be permanently discontinued.   
The development of any of the following severe toxicities due to treatment requires permanent 
dose reduction for that patient by 25% of the assigned dose for first occurrence, 50% of the 
initial assigned dose for second occurrence, and with treatment discontinued entirely in the event 
of a third occurrence (Table 6).   
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6.5. 
Treatment of Physician Choice (TPC) 
Treatment of Physician’s Choice (TPC) determined before randomization from only one of the 
following 4 single-agent treatment regimens and administered for locally advanced, unresectable 
or metastatic breast cancer as per NCCN guidelines 
(https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.) No combination of the four 
choices is permitted.  
 Eribulin (1.4 mg/m2 IV on Days 1 and 8 of a 21-day cycle North America sites, 1.23 
mg/m2 intravenously on Days 1 and 8 of a 21-day cycle  for European sites). See 
Section 6.5.1 
 Capecitabine (1000-1250 mg/m2 orally twice daily on Days 1-14 of a 21-day cycle). 
See Section 6.5.2 
 Gemcitabine (800-1200 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle). See 
Section 6.5.3 
 Vinorelbine (25 mg/m2 IV on Day 1 weekly). See Section 6.5.4 (Note: eligible 
patients with Grade 2 neuropathy should not be prescribed vinorelbine as TPC).  
An overview of dose, dose reduction , discontinuation  is provided in the 2 tables below (North 
America and EU). 
 
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VV-RIM-0002727 1.0 - Approved
Dose 
'\"\'"hen dose 
1-ednce? 
Dose 
1-eductions 
Di&eontin. 
Start. dose 
ad'uslment 
Start. dose 
ad:uslment 
Ca ecitabine 
1000-1250mgfm' twice in a day on day 1 and 14 of21 
During cycle 
Cycle 
+1 dose 
Eribnlin 
1.4 mgfm' on day 1 and day 8 ofa 21 day 
rcle 
On day l or 8: 
Hemaiologiral toricily 
Grade 3--t non hemalologiral toxicity 
Do nol gin day I o:r day 8 if: 
ANC 
< 1 OOOhmn' 
PLT 
< 75,000hmn' 
~ Q- ~- d=e- 2~-~1•-• -occ--'-=H~o~ld~un
- til=- -gr- 0-~ 1-'--1~0~0~%--i Grade 3-4 non hem AE 
2 occ. 
--=75=¾-•-~ Dose day 8 may be delayed on for 8 days 
3' occ 
50% 
max; omit dose if not resolved <2. If resolved 
4•• occ I 
Discontinue 
Q~de3 
1" occ 
Hold until gr 0-1 
75% 
E 
I 
:50% 
3 occ 
Discontinue 
Discontinue if gt~de -t or hold tmtil grade 0-1 if 
patient best interest 
Fo:r renal failm-e 
Coch:oft-Ga~t e nation 
Cale, creat clear. 
S 
50-120 ml/min 
30-50 m/min 
dose 
100"/. 
75% 
I 
to <2, then dose. on day 15 and restart next 
cycle on dav 28 with one dose reduction 
Reduce dose if: 
1. ANC < 10001mm' or ANC <10001mm' with 
fever and infection 
2. Pit < 25,000 or < 50,000/mm' requiring 
PLT transfusions 
3. grade 3-4 Non hematological AE 
4. dose omitted or delayed on day 8 at 
1Jrevious cvcle 
Dose reduce to 0 .7 mglm' for any AE 
requiring dose reduction while at 1.1 mglm' 
Discontinue for any AE requiring dose 
reduction while at 0. 7 mgfm' 
For 1-enal failnn 
Cale. c.reat. Clear. 
S 
:50-120mllm 
30-SOmlhn 
F01· hepatic impairment 
Child-
A 
U m m 
Child-Pu ,B 
0.7 m m'-
Gemcitabine 
800-1200 mg/m2 on day 1, day 8 day, day 15 
of28 da , ·de 
Hematological toricily: Grade 3 ANC: 
reduce to 75% - Grade 4 A.NC: Hold 
Grade 1-2 PLT: reduce to 75% - Grade 3 
PLT: Hold 
Grade 3--t non hemalolo · ral torici , ' 
Recommended dose modifications for 
myelosupp:ression on day of treatment: 
D 
A_i!iC 
& 
PLT 
8 
;:_1500 
& 
<1500 
or 
;:_100 000 
<100,000 
I >1200 I & I >75 ooo 
1000-
or 
50,000-
1199 
75,000 
I~:- I 
& I ~,o,ooo 
< 700 
or 
<50,000 
Day 15: Same as day 8 
Dose 
100% 
Hold 
I 100-;. 
75% 
1 50% 
Hold 
Hold or reduce by 50% for grade 3-4 non 
hematological toxicity until resolved 
Discontinue if unexplained dyspnea or 
evidence of severe pulmonary toxicity, severe 
hepatic toxicity, hemolytic uremic, capillary 
leak 
omes or PRES 
caution in atients with renal im aii:ment 
Gemcitabine shouJd be administered "Ri th 
caution in atients with he atir im ainne.nt 
Yinortlbine 
25 mgfm' weekly 
Grannloeytopenia 
Hepatic toricity (bilirubin) 
Dose adjlliitement based 
granulocytes 
Granul 
Dose 
;:_1500 
100% 
1,()()()c 
50% 
1499 
<1,000 
Hold and repeat count 
weekly discontinue if 
< 1,000 for > 3 weeks 
Tot Bili 
Dose 
{mg/~ 
::_2.0 
100% 
2.1-3.0 
50% 
>3.0 
25% 
I Hematolo~c and hepatic tori~~". 
use the lov;est dose Neuropathy. 
discontinue if 
. > 2 
No dose adaptation fo1· renal 
failm·e 
(see above) 


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Overview of Dose, dose reduction and discontinuation for TPC (Europe) 
 
 
VV-RIM-0002727 1.0 - Approved
Dooe 
'Whendosl' 
1'educe? 
Dooe 
reductions 
Diseonlin. 
SI.a.rt. dose 
ad'wtmenl 
Sta.rt. dose 
ad 'ustmenl 
Ca l'dtabinl' 
1000-125 Omglm' twice in a day on day I and 14 of21 
c. cle 
Any iNCIC gradl' 2 toridly 
Owing cyde 
Cyde 
·H dooe 
Eribnlin 
1.23 mglm' on day 1 and day 8 of a 21 day 
d e 
On day 1 or 8: 
Hemaiological toxidly 
Grade l-4 non hematologiul toricity 
Do not gin day 1 or day 8 if: 
A! C 
< 1,0001mm' 
Gemdtabine 
800-1200 mg/m1 on day 1, day 8 day, day 15 
of28 da 
·c.le 
Hematological to:rid~-: Grade 3 A.! C: 
reduce io 75%- Grade 4 Al C: Hold 
Gnde 1-2 PLT: reduce to 75% - Grade 3 
PLT: Hold 
Recommended dooe modifica,tions for 
myelosuppression on day of treatment: 
PLT 
< 75,0001mm' 
1,-,Gi_,1_d=t- 2~--1.~' _ooc
_...._~H~o-ld_un
_ til=. -gr- 0-
~ 1 ..... _1~0~0~%--i Gnde 3-4 non hem AE 
D 
A!,~C 
& 
PL T 
Dose 
Yinonlbine 
25 mglm' weekly 
Granulocytoptnia 
Hepatic toricily (bilirubin) 
Dose adjustement based 
granu!ocytes 
Granul 
Do.se 
1------+-----------------+---+----+--+-----t------t------+-
2 occ. 
~ 75~'¾-•-~ Do~da~·Smaybedelayedon for&days 
>1500 
& 
>100000 
100% 
3" ooc 
50% 
max; omit dose if not resolved .::2. Ihesolved 
<1500 
or 
<100,000 
Hold 
lo <2, ihen dose on day 15 and restart next 
cle on 
28 with one dose reduction 
4' occ 
Disl'onlinue 
Rrduct dos,e if: 
>--:-1,,.,-ooc--+--=H=-o-=-ld=-un
- tilcc. -gr--=-0-""1~-7:c5:-::'¾-:-.--t I. ANC < IOOO!mm' or ANC <1000/mm' with 
fever and infec,tion 
2 .. occ 
,--.,,50='¾~.---1 2. Ptt < 25,000 or < 50,000!mm' requiring 
PL T transfusions 
3' ooc 
Disronlinu._e----1 3. grade 3-4 Non hematologica] AE 
4. dose omitted or delayed on day 8 at 
revious 
de 
Disron.tinue if gndt 4 or hold until ~de 0-1 if 
patient best interest 
For renal failm"t' 
Coclmift-Gaull e nation 
50-120 ml/min 
30-50m/min 
dose 
100% 
75% 
Dose reduce to 0.67 mg/m' for any AE 
requiring dose red!mtion while at 0.97 mg/m1 
Discontinue for any AE reqwring dose 
reduction while at 0·.67 mglm' 
For l"t'nal failure 
Cale. creat. Clear. 
50-120 ml/m 
30-50ml/m 
For hepatk impairment 
Child-
A 
0.97m 
Child-Pu 
B 
0.67 m 
8 
>1200 
& 
>75 000 
100% 
1000-
or 
50,000-
75% 
1199 
75 000 
700-
& 
::50,000 
50% 
999 
< 700 
or 
<50,000 
Hold 
Da 15: Same as 
8 
Hold or reduce by 50% for grade 3-4 non 
ht>matological toxicity until resolved 
Discontinue if unexpJamed dyspneca or 
evidence of severe pulmonary toxicity, severe 
hepatic toxicity, hemolytic uremic, capillary 
leak 
drome 
Gemcrta me s o 
e a · · · te1-e<I ~ith 
,aution in atirnts mth renal im airm.ent 
Gemcitabine should be administ,e1-e<I ~ith 
caution in atients with he, atic im ainnent 
>1500 
100% 
1,000-
50% 
1499 
<1,000 
Hold and repe.at count 
week]y discontinue if 
< 1,000 for > 3 weeks 
Tot B.ili 
Dooe 
(mgldl) 
.::=_2.0 
100% 
2.1-3.0 
50% 
>3.0 
25% 
Hematologic and hepatic toricity: 
use the towest dose europathy: 
discontinue if . > 2 
No dost adaptati.on for renal 
fuilurt 
(see above) 


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6.5.1. 
Eribulin (Halaven) 
Eribulin (1.4 mg/m2 for North America sites, 1.23 mg/m2 for EU sites) is to be administered 
intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle undiluted or diluted in 100 
mL of 0.9% Sodium Chloride Injection, USP; do not dilute in or administer through an 
intravenous line containing solutions with dextrose. The recommended dose in patients with mild 
hepatic impairment (Child-Pugh A) is 1.1 mg/m2 for North American sites, 0.97 mg/m2 for EU 
sites administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle  The 
recommended dose in patients with moderate hepatic impairment (Child-Pugh B) is 0.7 mg/m2 
for North America, 0.67 mg/m2 for EU administered intravenously over 2 to 5 minutes on Days 1 
and 8 of a 21-day cycle. (See Appendix 7 for Child-Pugh scores in patients with hepatic 
impairment.) Assess for peripheral neuropathy and obtain complete blood cell counts prior to 
each dose. 
Recommended dose delays* 
Do not administer eribulin on Day 1 or Day 8 for any of the following: 
 ANC < 1,000/mm3 
 Platelets < 75,000/mm3 
 Grade 3 or 4 non-hematological toxicities 
The Day 8 dose may be delayed for a maximum of 1 week. 
 If toxicities do not resolve or improve to ≤ Grade 2 severity by Day 15, omit the dose. 
 If toxicities resolve or improve to ≤ Grade 2 severity by Day 15, administer eribulin 
at a reduced dose and initiate the next cycle no sooner than 2 weeks later. 
Recommended dose reductions 
 If a dose has been delayed for toxicity and toxicities have recovered to Grade 2 
severity or less, resume eribulin at a reduced dose as set out below. 
 Do not re-escalate eribulin dose after it has been reduced. 
 Permanently reduce the 1.4 mg/m2 eribulin dose to 1.1 mg/m2 (0.97mg/m2 for EU 
sites) for any of the following: 
 ANC <500/mm3 for >7 days  
 ANC <1,000/mm3 with fever or infection 
 
 Platelets <25,000/mm3 
 
 Platelets <50,000/mm3 requiring transfusion  
 Non-hematologic Grade 3 or 4 toxicities 
 
 Omission or delay of Day 8 eribulin dose in previous cycle for toxicity 
 Dose reduce to 0.7 mg/m2 (0.67 mg/m2 for EU sites) for any event requiring 
permanent dose reduction while receiving 1.1 mg/m2 (0.97 mg/m2 for EU sites) 
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 Discontinue eribulin for any occurrence of any event requiring permanent dose 
reduction while receiving 0.7 mg/m2 (0.67 mg/m2 for EU sites) 
*ANC = absolute neutrophil counts; Toxicities as per NCI-CTCAE version 3.0 
 
6.5.2. 
Capecitabine (Xeloda)  
Capecitabine  (1000-1250  mg/m2 )  is to be administered orally twice daily for 2 weeks followed 
by one-week rest period given as a 21-day cycle.  Capecitabine dose modification scheme 
described below is recommended for the management of adverse reactions. 
Toxicity NCIC Grades* 
During a Course of Therapy 
 
Dose Adjustment for Next 
Treatment (% of starting dose) 
 
Grade 1 
 
Maintain dose level 
 
Maintain dose level 
Grade 2 
1st appearance 
 
Interrupt until resolved to Grade 0-1 
 
100% 
2nd appearance 
75% 
3rd appearance 
50% 
4th appearance 
Discontinue treatment permanently 
- 
Grade 3 
1st appearance 
Interrupt until resolved to Grade 0-1 
75% 
2nd appearance 
50% 
3rd appearance 
Discontinue treatment permanently 
- 
Grade 4 
1st appearance 
Discontinue permanently OR 
If physician deems it to be in the 
patient’s best interest to continue, 
interrupt until resolved to Grade 0-1 
50% 
*National Cancer Institute of Canada Common Toxicity Criteria were used except for the hand-and-foot syndrome. 
In patients with moderate renal impairment (baseline creatinine clearance = 30 to 50 mL/min), a dose reduction to 
75% of the XELODA starting dose l (from 1250 mg/m2 to 950 mg/m2 twice daily) is recommended. 
 
6.5.3. 
Gemcitabine (Gemzar)  
Gemcitabine (800-1200 mg/m2) is to be administered intravenously diluted with 0.9% sodium 
chloride injection over 30 minutes on Days 1, 8, and 15 of each 28-day cycle. Recommended 
dose modifications for gemcitabine for myelosuppression on day of treatment are described 
below. 
Treatment Day 
Absolute neutrophil 
count (x 106/L) 
 
Platelet count 
(x 106/L) 
% of full dose 
 
Day 1 
≥1500 
and 
≥100,000 
100% 
 
less than 1500 
or 
less than 100,000 
Hold 
Day 8 and Day 15 
≥1200 
and 
>75,000 
100% 
 
1000-1199 
or 
50,000-75,000 
75% 
 
700-999 
and 
≥50,000 
50% 
 
<700 
or 
<50,000 
Hold 
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Dose Modifications for Non-Hematologic Adverse Reactions  
 Withhold Gemzar or reduce dose by 50% for other severe (Grade 3 or 4) non-
hematological toxicity until resolved.  
 No dose modifications are recommended for alopecia, nausea, or vomiting.  
Permanently discontinue Gemzar for any of the following:  
 Unexplained dyspnea or other evidence of severe pulmonary toxicity  
 Severe hepatic toxicity  
 Hemolytic-uremic syndrome  
 Capillary leak syndrome  
 Posterior reversible encephalopathy syndrome 
6.5.4. 
Vinorelbine (Navelbine)  
Vinorelbine (25 mg/m2 weekly) is to be administered as IV injection over 6-10 min. vinorelbine 
Injection must be diluted in either a syringe or IV bag using one of the recommended solutions. The 
diluted vinorelbine should be administered over 6 to 10 minutes into the side port of a free-flowing 
IV closest to the IV bag followed by flushing with at least 75 to 125 mL of one of the solutions. 
Syringe: The calculated dose of vinorelbine should be diluted to a concentration between 1.5 and 
3.0 mg/mL. The following solutions may be used for dilution: 
 5% Dextrose Injection, USP 
 
0.9% Sodium Chloride Injection, USP 
IV Bag: The calculated dose of vinorelbine should be diluted to a concentration between 0.5 and 
2 mg/mL. The following solutions may be used for dilution: 
 5% Dextrose Injection, USP 
 0.9% Sodium Chloride Injection, USP 
 0.45% Sodium Chloride Injection, USP 
 5% Dextrose and 0.45% Sodium Chloride Injection, USP 
Dose Modifications for Hematologic Toxicity: Neutrophil counts should be > 1,000 cells/mm3 
prior to the administration of NAVELBINE. Adjustments in the dosage  of vinorelbine should be 
based on neutrophil counts obtained on the day of treatment according to the following table. 
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Dose Adjustments Based on Neutrophil Counts 
Neutrophils on Day of 
Treatment (cells/mm3) 
Percentage of Starting Dose of vinorelbine 
>1,500 
100% 
1,000 to 1,499 
50% 
< 1,000 
Do not administer. Repeat neutrophil count in 1 week. If 3 
consecutive weekly doses are held because neutrophil count is 
<1,000 cells/mm3, discontinue NAVELBINE. 
Note: For patients who, during treatment with vinorelbine, experienced fever and/or sepsis while 
neutropenic or had 2 consecutive weekly doses held due to neutropenia, subsequent doses of 
NAVELBINE should be: 
>1,500 
75% 
1,000 to 1,499 
37.5% 
<1,000 
See above 
Dose Modifications for Hepatic Insufficiency: vinorelbine should be administered with caution to 
patients with hepatic insufficiency. In patients who develop hyperbilirubinemia during treatment 
with vinorelbine, the dose should be adjusted for total bilirubin (see below).  
Dose Modification Based on Total Bilirubin 
Total Bilirubin (mg/dL) 
Percentage of Starting Dose of vinorelbine 
<2.0 
100% 
2.1 to 3.0 
50% 
>3.0 
25% 
 
Dose Modifications for Concurrent Hematologic Toxicity and Hepatic Insufficiency: In 
patients with both hematologic toxicity and hepatic insufficiency, the lower of the doses based on 
the corresponding starting dose of vinorelbine determined from Tables above should be 
administered. 
Dose Modifications for Renal Insufficiency: No dose adjustments for vinorelbine are required for 
renal insufficiency. 
Dose Modifications for Neurotoxicity: If Grade >2 neurotoxicity develops, vinorelbine should be 
held until the toxicity resolves to < grade 1 and then restarted at a 50% of the starting dose of 
navelbine. If > Grade 2 neurotoxicity reoccurs after dose reduction to 50%, navelbine should be 
held until the toxicity resolves to < Grade 1 and then restarted at a 25% of the starting dose of 
navelbine. If > Grade 2 neurotoxicity reoccurs after dose reduction to 25%, navelbine should be 
discontinued 
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Permanently reduce the navelbine dose to 50% of the starting dose for any of the following: 
 Non-hematologic Grade 3 or 4 toxicities  
6.6. 
Management of Nausea and Vomiting for the TPC arm 
The management of nausea and vomiting as per the table below is recommended for patients in 
the TPC arm. 
Chemotherapy Induced Nausea Vomiting (CINV) guidelines 
High risk 
Not applicable 
Moderate risk 
IMMU-132 
Low risk 
Vinorelbine, eribulin, gemcitabine, capecitabine 
Minimal risk 
Not applicable 
Suggested anti-emetic regimen 
 
Anti-emetic regimen 
Delayed CINV 
Anti-emetic regimen 
High risk 
5HT3 antagonist + 
dexamethasone+ aprepitant 
High risk 
Dexamethasone (days 2-4) + 
Aprepitant (days 2-3) + lorazepam in 
selected patients 
Moderate risk 
5HT3 antagonist + 
dexamethasone+ aprepitant 
in selected cases 
Moderate risk 
Dexamethasone (days 2-4) + aprepitant 
day 2-3 (if used on day 1) + lorazepam 
in selected patients 
Low risk 
Dexamethasone or 
metoclopramide or 
prochlorperazine 
Low risk 
No anti-emetics 
Minimal risk 
No anti-emetics 
Minimal risk 
No anti-emetics 
7. 
STUDY EVALUATIONS 
Safety and tolerability will be evaluated from adverse events, standard safety laboratories (CBC 
with differential and platelet count, serum chemistries, and urinalysis), physical examination, and 
vital signs.  Adverse events will be classified according to the MedDRA system of preferred 
terms and system organ class, and all adverse events and abnormal laboratories will be classified 
for severity using NCI-CTCAE v4.03 toxicity grades. Descriptive statistics will be used to 
characterize adverse events, cytopenias, and other abnormal laboratories.  
Efficacy will be evaluated from CT scans or MRI studies, using RECIST 1.1 criteria given in 
Appendix 6 to classify tumor response, time to onset of objective response, duration of objective 
response, and time to progression. For each patient, the same imaging technique should be used 
throughout the trial.  Overall survival will be determined.  
 
 
 
  
 
 
  
 
 
VV-RIM-0002727 1.0 - Approved
CCI
CCI


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Patient-reported outcomes (PROs) provide a means of evaluating the subjective effect treatments 
have on patients and their quality of life (QOL) (Lipscomb et al, 2007). EORTC QLQ-C30 
(Appendix 5) will be completed at baseline, the beginning of every cycle, and the final study 
visit.  
8. 
ADVERSE EVENTS 
All patients must be carefully monitored for Adverse Events (AEs), including clinical laboratory 
tests.  AEs should be assessed in terms of their seriousness, intensity, and relationship to the 
study drug. For consistency, events are to be graded using the NCI-CTCAE version 4.03. 
An AE is any untoward medical occurrence; the event does not necessarily have a causal 
relationship with that treatment or usage.  AEs include the following: An exacerbation, or an 
unexpected increase in frequency or intensity of a pre-existing condition (other than condition 
under investigation), including intermittent or episodic conditions. 
1. Significant or unexpected worsening or exacerbation of the condition/indication under 
investigation 
2. A suspected drug interaction 
3. An intercurrent illness 
4. Any clinically-significant laboratory abnormality 
An AE does not include: 
1. Anticipated day-to-day fluctuations of any pre-existing conditions, including the disease 
under study 
2. Signs and symptoms of the disease under study that do not represent a significant 
worsening or exacerbation 
3. Expected progression of the disease under investigation 
8.1. 
Serious Adverse Events (SAEs) 
An AE that meets one or more of the following criteria/outcomes is classified as serious: 
1. Fatal 
2. Life-threatening 
3.  Disabling/incapacitating 
4.  Results in hospitalization or prolongs a hospital stay 
5.  A congenital abnormality 
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6. Other serious medical events may also be considered SAEs if they require medical or 
surgical intervention to prevent one of the outcomes listed above (e.g., allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions not resulting in hospitalization, development of drug 
dependency or drug abuse) 
An SAE does not include: 
1. Progression of disease. 
2. Hospitalization for a routine clinical procedure as stipulated by the protocol. 
Hospitalization for non-medical reasons (i.e., social admissions, hospitalizations for 
social, convenience or respite care). 
8.2. 
Reporting AEs/SAEs  
The Investigator is to report all AEs directly observed or spontaneously reported by patients 
using concise medical terminology.  Each patient will be questioned about AEs at each clinic or 
evaluation visit, asking, for example, “Since your last clinic visit, have you had any health 
problems?” 
All AEs will be reported following the first dose of study treatment through 30 days following 
the last day of administration of study treatment. Only treatment-related AEs will be captured 
from End of Treatment through the Safety Follow-up visit. All treatment-related AEs/SAEs that 
are ongoing at the time of the Safety Follow-up visit will be followed until resolution, return to 
baseline, or until they are Grade ≤ 1 (and following consultation and agreement by the Medical 
Monitor). During Follow-up visits in patients who discontinued therapy for reasons other than 
progression, any SAE determined by the Investigator to be potentially related to study treatment 
must also be reported. Whenever possible, a diagnosis should be given when signs and 
symptoms are due to common etiology (e.g., cough, runny nose, sneezing, sore throat, and head 
congestion should be reported as “upper respiratory infection”). 
In this protocol, disease progression is an efficacy endpoint and should not be reported as an AE. 
It is important to differentiate expected disease progression from an AE. Events that are clearly 
consistent with the expected pattern of disease progression should not be considered AEs. 
Expected disease progression refers to an event that is unequivocally related to disease 
progression, and that the clinical course is consistent with what would be expected for the 
patient’s disease. A clinical event in the setting of disease progression would be considered 
an AE if it could not be unequivocally attributed to or consistent with expected disease 
progression. 
A clinical laboratory AE is any laboratory value that is considered clinically significant by the 
Investigator and has caused a medical intervention, dose hold, dose reduction or schedule 
change. Laboratory abnormalities that have not required medical intervention should not be 
recorded as AEs (they will be analyzed and reported in the laboratory section of the clinical 
study report). 
All SAEs and pregnancies must be reported to the Sponsor or the Sponsor’s designee 
immediately, and no later than 24 hours of becoming aware of the event. 
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All SAEs and pregnancies should be repo1ied to the Sponsor's designee as per the repo1iing 
instructions provided on the SAE Fo1m Completion Guidelines and as stated on the SAE Fo1m . 
Repo1iing requirements for AEs are sUilllllarized in the following table (Table 7) 
Table 7: 
Reporting Requirements For Adverse Events 
Reporting Time 
Type of Report 
SERIOUS 
Within 24 hours 
Initial repo1t on designated SAE fo1m 
Within 5 calendar days 
Follow-up/Final repo1t on designated fo1m 
NON-SERIOUS 
Per CRF submission 
procedure 
Appropdate CRF pages 
8.3. 
Recording Information on AEs 
All AEs, whether observed by the Investigator, elicited from, or volunteered by the patient, will 
be recorded including: duration, severity, relationship to the study medication, ti·eatment, action 
taken with respect to the study medication and outcome. When possible, all events should be 
repo1ied in diagnostic te1ms or the most acceptable medical te1ms in order to interpret safety 
info1mation accurately. 
The investigator must review all laborato1y and test data and record any adverse events. The 
same fo1mat will be used as for other adverse events, regardless whether related to study therapy 
or not, including event severity grading, attl'ibution, and resolution. A summaiy listing of all 
adverse events occmTing during the past year on this study will be provided in progress repo1is 
repo1ied to regulato1y authorities. 
The Investigator will notify the Sponsor's designee if he/she becomes aware at any time, during 
or following the study, of the occmTence of death or new malignancy involving the paiiicipant of 
a clinical trial, even though the event may not appeai· to be dmg-related. 
8.4. 
Grading of AE Severity 
The severity of AEs will be graded using the NCI-CTCAE Version 4.03. For each event, the 
highest severity grade should be repo1ied. If a CTCAE criterion does not exist, the Investigator 
should use the grade or adjectives as described in Table 8. 
Table 8: 
Grading Of Adverse Event Severity 
Grade 
Adjective 
Description 
Grade 1 
Mild 
Does not interfere with patient's usual function 
Grade 2 
Moderate 
Interferes to some extent with patient's usual function 
Grade 3 
Severe 
Interferes significantly with patient's usual function 
Grade4 
Life-Threatening 
Results in a threat to life or in an incapacitating disability 
Grade 5 
Death 
Results in death (should be reported as a SAE) 
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A severe reaction (e.g., a severe headache) would not be classified as serious unless it met one of 
the criteria for SAE(s) listed above. 
8.5. 
Pregnancy 
The Sponsor’s designated contact must be notified of any patient becoming pregnant during the 
study, or of any spontaneous abortion or of any therapeutic abortion and any pregnancy must be 
followed until completion or termination of pregnancy.  The notification should be performed on 
the pregnancy form and be handled in the same manner as for SAEs. In the case of a live birth, 
the “normality” of the newborn can be assessed at the time of birth.  The “normality” of an 
aborted fetus can be assessed by gross visual inspection unless pre-abortion laboratory findings 
are suggestive of a congenital anomaly. 
8.6. 
Follow-up of Unresolved AEs  
Only AE and SAE possibly or probably related to study treatment will be followed-up beyond 
the 30-day period following the study treatment discontinuation. Such events should be followed 
until they resolve or are grade <1. Follow-up of these AE will reported in the CRF. 
8.7. 
Expedited Reporting 
In this trial, the Sponsor’s designee  is responsible for expedited reporting of any SAE 
considered to be SUSAR (Suspected Unexpected Serious Adverse Reaction). 
A SUSAR is any adverse event which meets the following 3 criteria 
 Serious Adverse Event.  An event meeting the SAE criteria in Section 8.1. 
 Suspected Adverse Reaction.  An event for which there is a reasonable possibility that 
there is a causal relationship between the study treatment and the event 
 Unexpected Adverse Reaction.  An event for which the nature or severity is not 
consistent with the applicable product information (e.g. Investigator's Brochure for an 
unapproved investigational product or package insert/summary of product 
characteristics for an approved product).  
The Sponsor’s designee will report all relevant information about suspected serious unexpected 
adverse reactions (SUSARs) to all applicable regulatory authorities in all participating countries, 
and via the Eudravigilance database (EVCTM), as required.  SUSARs determined to be fatal or 
life-threatening must be submitted not later than 7 calendar days after initial report of the 
information to the Sponsor’s designee (follow-up within an additional 8 days); otherwise 
SUSARs must be submitted within 15 calendar days.  
The Sponsor’s designee  will also report all SUSARs to the governing Ethics Committees and 
will inform all investigators, as required. 
8.8. 
Reporting death 
Death is an outcome of a serious adverse event and not a serious adverse event in itself. When 
death is an outcome, the event(s) resulting in death should be reported (e.g. “pulmonary 
embolism” with a fatal outcome).  
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The appropriate diagnosis or term should be recorded and assigned severity Grade 5; 
 In instances of death due to “Disease Progression” the cause of death should be 
indicated as the event or condition resulting in death to the extent possible (e.g. 
“respiratory failure” due to progressive TNBC). 
 Deaths that occur later than 30 days after the last study drug administration should be 
reported as SAEs only if assessed as related to the study treatment. 
8.9. 
Reporting to IRB/Ethics Committee (EC) 
SAEs will be reported to the local (or contract) Institutional Review Board (IRB)/Ethics 
Committee (EC) by the Investigator according to the IRB’s/EC’s policy and procedures. 
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the Health Competent Authorities and concerned Ethics Committees (ECs)/Institutional Review 
Boards (IRBs) in accordance with Directive 2001/20/EC or as per national regulatory 
requirements in participating countries. For the purpose of SUSARs reporting, only possibly or 
probably related SAEs (i.e., there is a reasonable possibility of causality) will be considered 
serious adverse drug reactions. 
8.10. 
Reporting to Health Authorities 
The Sponsor’s designee will be responsible for reporting all AEs and SAEs to the appropriate 
regulatory authorities (e.g., U.S. FDA), Investigators, and central IRB in accordance with all 
applicable regulations and guidance documents. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Determination of Sample Size 
A hazard ratio (HR) of 0.667, likely corresponding to a 50% improvement in PFS, would be 
considered to be clinically meaningful in this relapsed/refractory locally advanced or metastatic 
TNBC patient population.  Four hundred and eighty-eight patients (488) patients are anticipated 
to be enrolled.  The population of patients with brain metastases will be capped at 15 % (N=74) 
of the trial population.  The primary PFS analysis will be performed when 425 investigator 
defined PFS events have occurred in all patients randomized as long as 315 or more PFS events 
have also occurred, according to Independent Review Committee (IRC) review, as defined for 
the primary analysis in the primary analysis population of patients without brain metastases 
(BM-ve population).  Assuming at most 15% of patients have brain metastases and there are 13% 
or fewer IRC events compared to investigator review, it would be expected that there would be at 
least 315 IRC events in the BM-ve population at the time 425 investigator PFS events have been 
observed amongst all patients randomized.  If the true HR is 0.667 in the IRC review of the BM-
ve population, the study will have at least 95% power to detect a statistically significant 
improvement in PFS, with a two-sided type 1 error rate of 5%, if data are analysed after 315 IRC 
PFS.  PFS estimates in this patient population vary from 1.7 to 4.2 months (3 months average).  
For an estimate of median PFS of 3 months in the control TPC group, and assuming a 24-month 
enrollment period,  it is expected the primary PFS analysis will be performed after a minimum 
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follow-up of approximately 4 months.  OS will be analyzed at the time of the PFS analysis and 
also after 330 deaths have occurred in the primary analysis population of randomized patients 
without brain metastases.  The study will have approximately 89.5% power to detect an 
improvement in overall survival in the BM-ve population, with a two-sided 5% type-1 error rate, 
assuming that 72% of the planned number of deaths in BM-ve population have occurred at the 
time of the interim analysis (i.e., 238 deaths), and the true HR for OS is 0.7.  Assuming a 10-
month median in the control arm, a HR of 0.7 would likely correspond to a 4.3-month 
improvement.   The final analysis of OS is predicted to occur after a minimum follow-up of 17 
months, 13 months after the primary analysis of PFS. 
9.2. 
Interim analysis 
There will be an interim analysis of overall survival at the time of the final PFS analysis. A Lan-
DeMets spending function that approximates O’Brien/Fleming stopping boundaries will be 
applied to the interim OS analysis, where the 2-sided significance level applied is determined by 
(t) = 2-2(-z/2/t).  In the equation, t is the number of OS events occurring at the interim 
divided by the number expected at the final analysis (i.e., 330) of the BM-ve population.  If the 
final number of events differs from expected, the final significance level will be adjusted so that 
the overall alpha is controlled given the significance level applied at the first analysis.  The PFS 
ITT analysis will only be declared as statistically significant if both the PFS BM-ve and OS BM-
ve analyses have also been declared as statistically significant.  However, given the PFS ITT 
analysis will not be updated at the final OS analysis, a 2-sided significance level of 0.05 will be 
applied to this endpoint if and when both PFS and OS are statistically significant in the BM-ve 
population. In addition, OS in the ITT population will only be tested once PFS in the ITT 
population has been declared statistically significant. If this occurs at the time of the interim 
analysis, OS in the ITT population will be tested at the same adjusted alpha level computed for 
the analysis of OS in the BM-ve population. The significance level for the final analysis of OS in 
the ITT population will be determined by the Lan-DeMets spending function to ensure alpha is 
controlled at a 2-sided alpha of 0.05 at the final OS analysis, if OS analyses in the ITT 
population is also conducted at the time of PFS analysis.   
9.3. 
Efficacy Analyses 
The primary analysis population consists of all ITT patients without brain metastases labelled 
throughout as the BM-ve population, defined as all randomized patients who were randomized to 
the strata of no baseline brain metastasis at the time of randomization.   Analyses will also be 
performed amongst all randomized patients, regardless of whether they have brain metastases, 
labelled throughout as the ITT population. 
To strongly control type I error across populations and the two key endpoints of IRC PFS and 
overall survival (OS), a hierarchical testing strategy will be performed as displayed below, where 
a given hypothesis can only be declared statistically significant if all hypotheses above it in the 
hierarchy are also statistically significant.   If fewer than 30 patients with brain metastases are 
recruited, analyses in the ITT population will be removed from the hierarchy. 
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Overall survival will be analysed both at the time of the primary PFS analysis and, if not 
statistically significant at this time, later when a total of 330 deaths have occurred in the primary 
analysis population of randomized patients without brain metastases.    A Lan-DeMets spending 
function that approximates O’Brien/Fleming stopping boundaries will be applied to the interim 
OS analysis, where the 2-sided significance level applied is determined by (t) = 2-2(-z/2/t).  
In the equation, t is the number of OS events occurring at the interim divided by the number 
expected at the final analysis (i.e., 330) of the BM-ve population.  If the final number of events 
differs from expected, the final significance level will be adjusted so that the overall alpha is 
controlled given the significance level applied at the first analysis.  The PFS ITT analysis will 
only be declared as statistically significant if both the PFS BM-ve and OS BM-ve analyses have 
also been declared as statistically significant.  However, given the PFS ITT analysis will not be 
updated at the final OS analysis, a 2-sided significance level of 0.05 will be applied to this 
endpoint if and when both PFS and OS are statistically significant in the BM-ve population. In 
addition, OS in the ITT population will only be tested once PFS in the ITT population has been 
declared statistically significant. If this occurs at the time of the interim analysis, OS in the ITT 
population will be tested at the same adjusted alpha level computed for the analysis of OS in the 
BM-ve population. The significance level for the final analysis of OS in the ITT population will 
be determined by the Lan-DeMets spending function to ensure alpha is controlled at a 2-sided 
alpha of 0.05 at the final OS analysis, if OS analyses in the ITT population is also conducted at 
the time of PFS analysis.  The testing procedures and corresponding alpha levels for type I error 
rate control are depicted in the following diagram.  
 
 
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Efficacy analyses will be performed on an intent-to-treat basis so that all patients randomized in 
the relevant population will be included.  As a sensitivity analysis, efficacy will be also analyzed 
based on the Efficacy-Analyzable population, defined as all eligible, randomized and treated 
patients with at least one cycle of IMMU-132 or TPC and available follow-up radiological 
assessment data.  
Imaging evidence of efficacy will be obtained from CT or MRI scans using RECIST 1.1 criteria 
to classify tumor response, time to onset of objective response, duration of objective response, 
and time to progression. Starting with the initial dose of sacituzumab govitecan or TPC, CT or 
MRI scans will be obtained every 6 weeks for 36 weeks, then every 9 weeks thereafter, until the 
occurrence of progression of disease requiring discontinuation of further treatment.  For each 
patient, the same imaging technique should be used throughout the trial. Using descriptive 
statistics, these metrics will be tabulated and compared between the two treatment arms.   
A stratified log-rank test stratified by randomization strata will be used to compare the treatment 
groups for the time-to-event endpoints of PFS and Overall Survival Estimates of hazard ratios 
and 95% confidence intervals of PFS and OS will be based on a  stratified Cox proportional 
hazard regression model with treatment arm as the only covariate.  
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Yes 
PFS in ITT 
2-sided alpha = 0.05 
OS (interim) in ITT 
2-sided Lan-DeMets alpha 
Wa it t ill OS data fully mature 
OS (fina l) in ITT 
2-sided Lan-De Mets alp ha 
ad'usted at fina l 
PFS in BM-ve 
2-sided alpha = 0.05 
OS (inte rim) in BM-ve 
2-sided Lan-DeMets alpha 
Yes 
Testing procedure 
completed 
No 
Wait t ill OS data fu lly mature 
OS (fi nal) in BM-ve 
2-sided Lan-DeMets alpha 
adjusted at fina l 
PFSin ITT 
2-sided alpha = 0.05 
OS (final ) in ITT 
2-sided Lan-DeMets alpha 
ad·usted at fi nal 


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The PFS, OS, ORR, duration of response, and time to onset of response will be tabulated and 
compared between the two treatment groups. 
PFS will be measured by an independent centralized and blinded group of radiology experts who 
will be assessing tumor response using RECIST 1.1 criteria. FDA definitions and guidance as 
described in Guidance for Industry: Clinical Trials Endpoints for the Approval of Cancer Drugs 
and Biologics (December 2018) and Clinical Trial Endpoints for the Approval of Non-Small Cell 
Lung Cancer Drugs and Biologics (April 2015) will be used.   
Target lesions will be assessed by CT scans or MRIs according to the same schedule in both 
treatment arms.  PFS will be defined as the time from randomization until objective tumor 
progression or death, whichever comes first. The date of progression will be the earliest time 
when any tumor progression is observed based on RECIST 1.1 (see Appendix 6). It will be the 
date of the last observation or radiological assessment of target lesions that shows a predefined 
increase (20%+) in the sum of the target lesion measurements, compared to the previous 
minimum, or the appearance of new lesions or unequivocal progression of non-target lesions.  
The following censoring rules will be applied to the primary analysis of PFS: 
a. A patient who dies during follow-up period for survival without documented 
progressive disease will be considered to have an event for PFS analysis. 
b. Patients who do not have progression and are alive will be censored at last date of 
radiographic assessment without documented progressive disease. 
c. Patients that progress or die following more than one missed scheduled visit will be 
censored at the last date of radiographic assessment without documented progressive 
disease. 
d. Patients in the follow-up period for progression who receive alternative anticancer 
treatment before documented progressive disease will be censored at the last date of 
radiographic assessment without documented progressive disease prior to receiving 
alternative anticancer treatment. 
e. Patients without baseline tumor assessments or without additional follow-up data will 
be censored at the date of randomization. However, if such a patient dies no later than 
the time of the second scheduled assessment as defined in the protocol, this patient 
will be considered to have an event at the date of death. 
 
The primary analysis of PFS will be based on the assessment of the central reviewer; additional 
sensitivity analyses will be performed based on definitions of PFS as defined in the Statistical 
Analysis Plan including the investigator’s assessment.  
OS will be measured from the date of randomization to death from any cause.  Patients not 
known to have died at last follow-up are censored on the date they were last known to be alive. 
Patients are censored at the date of initiation of therapy (Day 1) if no additional data are 
obtained. 
All statistical analyses will be performed using SAS® (SAS Institute, Version 9.2 or later, Cary, 
NC). Summary tables and listings will also be prepared using SAS. 
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All summaries will present analyses by treatment arm and overall. Continuous data will be 
summarized using descriptive statistics: n, mean, median, standard deviation, minimum and 
maximum. Categorical data will be summarized using counts and percentages.  
In an exploratory analysis of PFS, a Cox proportional hazard regression analysis (Cox 1972) 
stratified by the randomization strata will be performed to determine which factors are 
significantly associated with PFS.  Univariate and multivariate Cox regression analyses will be 
performed including treatment arm and selected prognostic factors.  Univariate prognostic 
factors that are significant at the 0.10 level will be included in the multivariate model.  The 
resulting hazard ratios for each prognostic factor, associated 95% confidence intervals, and p 
values will be reported for the univariate and multivariate models.  Prognostic factors included in 
the analyses will be finalized prior to database lock and included in the Statistical Analysis Plan.  
In addition, subgroup analyses of PFS will be performed based on each level of the stratification 
factors, and important baseline demographics and disease characteristic factors. 
All analyses and descriptive summaries will be based on observed data. Unless otherwise 
specified missing data will not be imputed or “carried-forward”. 
Quality of life assessment 
Descriptive statistics (mean, standard error, minimum, and maximum) will be used to evaluate 
the changes from baseline in EORTC QLQ-C30 scores for each visit by treatment arm. 
Based on the labelling of capecitabine, gemcitabine, eribulin and vinorelbine, as well the known 
toxicities of IMMU-132 in the Phase I/II study, the major expected toxicities in this study are 
summarized below (Table 9). 
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Table 9: 
Anticipated toxicities of IMMU-132 and control drugs 
ll'\-IMU-13 2 
Capecitabine 
Vinorelbine 
Gemcitabine 
Eribulin 
Cutaneous 
Rash 
X 
X 
Hair loss 
X 
X 
Hand-foot syndrome 
X 
Cardio-Circulatory 
Swelling 
X 
X 
Hea1t palpitations 
X 
Pain 
Muscle pain 
X 
Joint pain 
X 
Gastrointestinal 
Decrease appetite 
X 
Nausea 
X 
X 
X 
X 
X 
Vomiting 
X 
X 
X 
X 
X 
Constipation 
X 
X 
Diarrhea 
X 
X 
X 
Abdominal pain 
X 
X 
Fecal incontinence 
X 
X 
X 
Sleep/Wake 
Fatigue 
X 
X 
X 
X 
Respiratory 
Shortness of breath 
X 
X 
X 
X 
X 
Neurological 
Numbness & tingling 
X 
X 
X 
Miscellaneous 
Chills 
X 
X 
X 
X 
Nose bleed 
X 
X 
Oral 
Difficulty swallowing 
X 
Mouth/throat sores 
X 
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9.4. 
Safety Analyses 
All patients administered at least one dose of IMMU-132 or TPC will be included in the 
evaluation of safety. 
The total amount of study drug and number of cycles and doses received will be summarized by 
treatment group. 
Safety and tolerability will be evaluated based on adverse events, standard safety laboratories 
(CBC with differential and platelet count, serum chemistries, and urinalysis), physical 
examination, ECG, and vital signs (heart rate, systolic and diastolic blood pressure, respiratory rate, 
and body temperature).   
The frequency and severity of adverse events (AEs), classified by MedDRA, will be summarized 
by treatment group and overall using MedDRA Preferred Term and System Organ Class (SOC).  
An AE that occurs more than once within each patient will be counted only once in the 
summaries, using the worst NCI-CTCAE grade and relationship category.  AEs will be 
consolidated using the worst NCI-CTCAE grade and relationship category observed for 
classification into each MedDRA SOC summary.  
AEs leading to death or to discontinuation from treatment, as well as all SAEs will be 
summarized separately.  A listing of all death information will be generated. The reasons for 
study discontinuation will also be summarized for each treatment group. 
Both actual and change-from-baseline data on vital signs and ECG intervals (with particular 
emphasis on corrected QT interval) will be summarized using descriptive statistics by treatment 
group for each study time-point. Percentages with abnormal ECGs will be presented at each 
scheduled time point.  
Routine safety laboratories, based on hematology and routine serum chemistry data (glucose, 
creatinine, BUN, total bilirubin, AST, ALT, LDH, alkaline phosphatase, serum albumin, total 
protein, Na, K, calcium, Cl, CO2, magnesium and phosphate), will be summarized using values 
at each visit and change from baseline using descriptive statistics for each treatment group.  
Laboratory test results for platelets, neutrophils, white blood count, lymphocytes and hemoglobin 
will be graded according to NCI-CTCAE severity grade.  The worst NCI-CTCAE grade 
observed on-treatment will be tabulated for each lab parameter and presented in a frequency 
table by baseline grade.  For parameters for which a NCI-CTCAE scale does not exist, the 
proportion of patients with abnormal values will be summarized by treatment group. 
Data on anti-drug antibody responses will be listed and summarized by descriptive statistics.   
 
 
 
 
 
 
 
 
   
 
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10. 
TREATMENT COMPLIANCE 
IMMU-132 will be administered at scheduled study centers under the supervision of the 
Investigator or sub-investigator(s).  The pharmacist will maintain records of study drug receipt, 
preparation, and dispensing, including the applicable lot numbers, patient’s height, weight and 
total drug administered in milligrams.  Any discrepancy between the calculated dose and dose 
administered and the reason for the discrepancy must be recorded in the source documents and 
on appropriate CRF.  
11. 
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor has ethical, legal and scientific obligations to follow this study carefully in a 
detailed and orderly manner in accordance with established research principles and applicable 
regulations.  Monitoring visits to the study site will be conducted periodically during the study to 
ensure that good clinical practice (GCP) and all aspects of the protocol are followed.  The trial 
site may also be subject to review by the IRB/IEC, to quality assurance audits performed by the 
Sponsor’s designee and/or to inspection by appropriate regulatory authorities. Investigator(s) and 
their relevant personnel must agree to be available and participate with visits conducted at a 
reasonable time in a reasonable manner, and the Investigator/Institution must guarantee direct 
access to source documents by Immunomedics and its designee, and appropriate regulatory 
authorities. 
Regulatory authorities worldwide may also audit the Investigator during or after the study.  The 
Investigator should contact the Sponsor’s designated contact immediately if this occurs, and 
must fully cooperate with regulatory authority audits conducted at a reasonable time in a 
reasonable manner.  
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12. 
DATA HANDLING AND RECORD KEEPING  
12.1. 
Electronic Case Report Forms (eCRFs) 
An eCRF is required and must be completed for each enrolled patient.  The completed original 
eCRFs are the sole property of Immunomedics and should not be made available in any form to 
third parties, except for authorized representatives of appropriate regulatory authorities, without 
written permission from Immunomedics. 
It is the Investigator's responsibility to ensure completion and to review and approve all eCRFs.  
eCRFs must be signed by the Investigator or by an authorized staff member.  These signatures 
serve to attest that the information contained on the CRFs is true.  At all times, the Investigator 
has final personal responsibility for the accuracy and authenticity of all clinical and laboratory 
data entered on the eCRFs.  Patient source documents are the physician's patient records 
maintained at the study site.  In most cases, the source documents will be the hospital's or the 
physician's chart.  In cases where the source documents are the hospital or the physician's chart, 
the information collected on the eCRFs must match those charts.  In some cases, a portion of the 
source documents for a given study site may be the eCRFs.  The Investigator must agree which 
items will be recorded in the source documents and for which items the eCRF will stand as the 
source document. 
Corrections to the eCRF must be initialed and dated by the person making the correction (ICH 
E6 4.9.3).  
12.2. 
Record Retention 
Records and documents pertaining to the conduct of this study, including eCRFs, source 
documents, consent forms, laboratory test results, and medication inventory records must be 
retained by the Investigator for at least 15 years. No study records shall be destroyed without 
prior authorization from Immunomedics. For studies conducted outside the United States under a 
US IND, the Investigator must also comply with US FDA IND regulations, ICH guidelines, and 
with the regulations of the relevant national and local health authorities. Current US federal law 
requires an Investigator to maintain such records for a period of two years following approval of 
a Biologic License Application, or, if the Biologic License Application is not approved, until two 
years following notification by Immunomedics that the clinical investigations have been 
discontinued. 
13. 
ADMINISTRATIVE REQUIREMENTS 
13.1. 
Good Clinical Practice 
The study will be conducted in accordance with the ICH for GCP and the appropriate local and 
national regulatory requirement(s).  The Investigator will be thoroughly familiar with the 
appropriate use of the study medications as described in the protocol and Investigator’s 
Brochure.  Essential clinical documents will be maintained to demonstrate the validity of the 
study and the integrity of the data collected.  Master files for this study should be established at 
the beginning of the study, maintained for the duration of the study, and retained according to the 
appropriate regulations. 
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13.2. 
Ethical Considerations 
This study is planned to be conducted both in the North America, Europe, and potentially 
elsewhere. European regulatory agencies require that the study will be conducted in accordance 
with ethical principles founded in the Declaration of Helsinki.  The trial will be performed in 
accordance with ICH GCP guidelines, the Declaration of Helsinki, 18th World Medical 
Assembly, Helsinki, Finland, 1964 and later revisions (as mandated for European trials), and 
applicable local regulatory requirements and laws.  In the United States, ethical protection is 
provided by compliance with GCPs as described in ICH and 21 CRF 50 (Protection of Human 
Subjects). 
The Institutional Review Board (IRB) and the Institutional Ethics Committee (IEC) will review 
all appropriate study documentation in order to safeguard the rights, safety and well-being of the 
patients. The study will only be conducted at sites where IRB/IEC approval has been obtained. 
The Investigator is responsible for providing their IRB/IEC with any required study documents, 
progress reports and safety updates and is responsible for notifying the IRB/IEC promptly of all 
SAEs occurring at the site. 
All correspondence with the IRB/IEC should be retained in the Investigator File. Copies of 
IRB/IEC approvals should be forwarded to Immunomedics or the designee. 
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the patients.  In that 
event, the Investigator must notify the IRB/IEC and Immunomedics or its designee in writing 
within 5 working days after the implementation. 
13.3. 
Patient Information and Consent 
It is the responsibility of the Investigator to give each patient (or the patient’s acceptable 
representative) full and adequate verbal and written information regarding the objective and 
procedures of the trial including the possible risks and benefits involved.  Written patient 
information, approved by the IRB/IEC, must be given to each patient before any trial-related 
procedure is undertaken.  During the consent process, the patient must be informed about their 
right to withdraw from the trial at any time.  The patient must also be given ample time to read 
the written informed consent form and have all study-related questions answered to the 
satisfaction of the patient (or the patient’s legally acceptable representative).  It is the 
responsibility of the Investigator to obtain a signature from each patient, the patient’s legally 
acceptable representative (if applicable), and from the persons conducting the informed consent 
discussion prior to undertaking any trial-related procedure.  The patient (or the patient’s legally 
acceptable representative) must be given a copy of the signed and dated informed consent form.  
The Investigator is also responsible for providing the patient (or the patient’s legally acceptable 
representative) with any clinical trial updates that may affect the subject’s willingness to 
continue participation in the study.  The informed consent process must be documented in the 
patient’s medical or source chart. 
The written patient information must not be changed without prior approval by Immunomedics 
or its designee and the IRB/IEC.   
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Per ICH E6 4.3.3, it is recommended that the Investigator notify the patient’s primary care 
physician of the subject’s participation in the trial if the subject agrees to the Investigator 
informing the primary care physician. 
13.4. 
Protocol Compliance 
The Investigator will conduct the study in compliance with the protocol provided by 
Immunomedics or its designee, and given approval by the IRB/IEC and the appropriate 
regulatory authorities. Modifications to the protocol should not be made without agreement of 
both the Investigator and Immunomedics or its designee.  Changes to the protocol will require 
written IRB/IEC approval prior to implementation, except when the modification is needed to 
eliminate an immediate hazard(s) to the patient.  The IRB/IEC may provide, if applicable, 
regulatory authorities permit, expedited review and approval for minor change(s) in ongoing 
studies that have the approval of the IRB/IEC.  The Sponsor’s designee will submit all protocol 
modifications to the regulatory authorities in accordance with the governing regulations. 
When immediate deviation from the protocol is required to eliminate an immediate hazard(s) to 
patients, the Investigator will contact the Sponsor’s designee, if circumstances permit, to discuss 
the planned course of action. Any departures from the protocol must be fully documented in the 
patient’s CRF and source documentation.  
13.5. 
Site Monitoring and On-Site Audits 
Monitoring and auditing procedures developed by Immunomedics or its designee will be 
followed, in order to comply with ICH/GCP; FDA and all applicable guidelines.  On-site review 
of patient’s eCRFs, EMR or paper source documentation for completeness as well as a review of 
all applicable regulatory documents will be performed.  All available source documents should 
be obtained by the Investigator and provided to the Sponsor’s designee at each monitoring visit. 
The site monitor will ensure that the investigation is conducted according to protocol design and 
regulatory requirements by frequent communications. 
Regulatory authorities, the IRB/IEC, and/or Immunomedics’ clinical quality assurance group or 
designee may request access to all source documents, patient’s eCRFs, and other study 
documentation for on-site audit or inspection. Direct access to these documents must be 
guaranteed by the Investigator, who must cooperate and provide support at all times for these 
activities. 
13.6. 
Patient Data Protection 
Privacy Act Compliance.  Information collected in this clinical trial is subject to the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA) as described in 45 CFR 160 and 
45 CFR 164.  The study Investigator is responsible for informing patients of their rights under 
HIPAA, and obtaining any necessary HIPAA authorizations.  In compliance with the provisions 
of that policy, Immunomedics or designee will not collect any protected health information, and 
will only collect de-identified health information.  Any clinical study information referred to in 
this section is understood to be compliant with the provisions of the Privacy Act. 
The information obtained during the conduct of this clinical study is confidential, and disclosure 
to third parties other than those noted below is prohibited.  Information obtained during the 
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conduct of this study will be used by Immunomedics or designee in connection with the 
development of the study drug.  The study Investigator is obliged to provide Immunomedics or 
designee with complete test results and all data developed in this study.  This information may be 
disclosed to other physicians participating in the study, to the FDA, or to national and local 
health authorities.  To ensure compliance with all current Federal Regulations and the ICH/GCP 
guidelines, data generated by this study must be available for inspection upon request by 
representatives of the FDA, national and local health authorities, Immunomedics, designee, and 
the IRB/EC for each study site. 
13.7. 
Financial Disclosure 
In accordance with 21 CFR Part 54, FDA requires that certain financial interests and 
arrangements between sponsors of clinical investigations be disclosed in marketing applications.  
Since the results of this study may eventually be used in a marketing application, compliance 
with this Federal statute is essential.  In order to comply with the provisions of this regulation, 
Immunomedics requests that every Investigator and sub-Investigator mentioned on FDA Form 
1572 fill out a financial disclosure form.  Under the provisions of 21 CFR Part 54, the term 
clinical Investigator includes the spouse and each dependent child of the Investigator. 
The provisions of 21 CFR Part 54 specify disclosure of significant equity interests in the Sponsor 
that exceed $50,000, or significant payments of other sorts made by the Sponsor to the 
Investigator that have a monetary value of more than $25,000, exclusive of the costs of 
conducting the clinical study or other clinical studies (e.g., grants to fund ongoing research, 
compensation in the form of equipment or retainers for ongoing consultation), during the time 
the clinical Investigator is carrying out the study or for 1 year following the completion of the 
study.  If a change in financial interest occurs throughout the study, the Investigator is obligated 
to notify Immunomedics. 
To assist Immunomedics, Inc., or designee in providing the FDA with the required information, 
please complete the financial disclosure form and return the original signed copy.  All 
information provided in the financial disclosure form will be regarded as strictly confidential and 
will only be disclosed to the FDA. 
13.8. 
Sponsor Discontinuation Criteria 
Immunomedics, Inc. reserves the right to discontinue the trial prior to inclusion of the intended 
number of patients, but intends only to exercise this right for valid scientific or administrative 
reasons.  After such a decision, the Investigator must contact all participating patients within a 
time period set by the Sponsor.  In the unlikely event of premature termination or discontinuation 
of the study, in the event the Investigator believes a patient is continuing to receive clinical 
benefit, the Sponsor will discuss options with the Investigator in order to ensure continuing 
supply of sacituzumab govitecan. 
As directed by the Sponsor’s designee, all study materials will be collected and all CRFs 
completed to the greatest extent possible. 
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14. 
DISSEMINATION AND PUBLICATION OF RESULTS 
The conditions regulating dissemination of the information derived from this clinical study are 
described in the Clinical Trial Agreement. 
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15. 
REFERENCES 
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spreading of human cancer. J Clin Oncol. 2007;25:Abst 10510. 
Andre F, Zielinski CC. Optimal strategies for the treatment of metastatic triple-negative breast 
cancer with currently approved agents. Ann Oncol. 2012; 23 (suppl 6): vi46-vi51. 
Bardia A, Vahdat LT, Mayer IA et al. Therapy of refractory/relapsed metastatic triple-negative 
breast cancer (TNBC) with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab 
govitecan (IMMU-132): Phase I/II clinical experience. J Clin Oncol. ASCO Annual Meeting 
2015;33(15):1016. 
Bardia A, Mayer IA, Diamond JR et al. Efficacy and Safety of Anti-Trop-2 Antibody Drug 
Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic 
Triple-Negative Breast Cancer. J Clin Oncol  2017 35:2141-2148. 
Basu A, Goldenberg DM, Stein R. The epithelial/carcinoma antigen EGP-1, recognized by 
monoclonal antibody RS7-3G11, is phosphorylated on serine 303. Int J Cancer. 1995;62:472-9. 
Benson B, Ajani JA, Catalano RB et al. (2004) Recommended guidelines for the treatment of 
cancer treatment-induced diarrhea. J Clin Oncol. 2004; 22:2918-26. 
Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM. Humanized anti-Trop-2 
IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers:  Preclinical studies in 
human cancer xenograft models and monkeys. Clin Cancer Res. 2011;17:3157-69. 
Cardillo TM, Govindan SV, Sharkey RM, et al. Sacituzumab Govitecan (IMMU-132), an anti-
Trop-2/SN-38 antibody-drug conjugate: characterization and efficacy in pancreatic, gastric, and 
other cancers. Bioconj Chem. 2015;26:991-31. 
Cox, DR  Regression models and life tables (with discussion).  Journal of the Royal Statistical 
Society. 1972;B34:187-220. 
Fang YJ, Lu ZH, Wang GQ, et al. Elevated expressions of MMP7, TROP2, and surviving are 
associated with survival, disease recurrence, and liver metastasis of colon cancer. Int J 
Colorectal Dis. 2009;24:875-84. 
Forero-Torres A, Varley KE, Abramson VG, et al. TBCRC 019: A phase II trial of 
nanoparticle albumin-bound paclitaxel with or without the anti-death receptor 5 monoclonal 
antibody tigatuzumab in patients with triple negative breast cancer. Clin. Cancer Res. 
2015;online. 
Goldenberg, DM, Cardillo TM, Govindan SV, Rossi EA, and Sharkey RM.  Trop-2 is a novel 
target for solid cancer therapy with sacituzumab govitecan (IMMU-132, and antibody drug 
conjugate (ADC). Oncotarget. 2015; 6(26): 22496-512. 
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Govindan SV, Cardillo TM, Moon SJ, Hansen HJ, Goldenberg DM. CEACAM5-targeted 
therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 
immunoconjugates. Clin Cancer Res. 2009;15:6052-61. 
Isakoff SJ, Mayer EL, Lei H, et al. TBCRC009: A multicenter phase II clinical trial of 
platinum monotherapy with biomarker assessment in metastatic triple-negative breast 
cancer.  J Clin Oncol. 2015;33:1-10;online. 
Kris MG, Hesketh PJ, Somerfield MR et al. American Society of Clinical Oncology guidelines 
for antiemetics in oncology: Update  J Clin Oncol.  2006;24:2932-47.  
Lipscomb J et al. Patient-reported outcomes in cancer: a review of recent research and policy initiatives. 
CA Cancer J Clin 2007 57(5):278-300. 
Mancini, P, Angeloni A, Risi E, et al. Standard of care and promising new agents for Triple-
Negative metastatic breast cancer. Cancers (Basel). 2014; 6(4):2187-223. 
Mathijssen RH, van Alphen RJ, Verweij J, et al. Clinical pharmacokinetics and metabolism of 
irinotecan (CPT-11). Clin Cancer Res. 2001;7:2182-94. 
Moon SJ, Tat F, Sheerin A et al. Cross-linker evaluation in the design of antibody-SN-38 
conjugates for cancer therapy. Cancer Research: April 15, 2010; Volume 70, Issue 8, 
Supplement 1 and Proc. Amer. Assoc. Cancer Res. 101st Annual Meeting, 51:591-592 (Abstract. 
#2349), 2010. doi: 10.1158/1538-7445.AM10-2439. 
O’Shaughnessy J, Lee Schwartzberg L, Danso MA et al.,  Phase III Study of Iniparib Plus 
Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin in Patients With Metastatic 
Triple-Negative Breast Cancer J Clin Oncol. 2014.55.2984. 
Perez E.A., Patel T. and Moreno-Aspitia A. Efficacy of ixbepilone in ER/PR/HER-2 negative 
(triple-negative) breast cancer. Breast Cancer Res Treat.  2010 121(2):261-71. 
SAS Institute Inc. (2010).  SAS/STAT® 9.2 User’s guide.  Cary, NC: SAS Institute Inc. 
Sharkey RM, McBride WJ, Cardillo TM, et al. Enhanced delivery of SN-38 to human tumor 
xenografts with an anti-Trop-2-SN-38 antibody conjugate (sacituzumab govitecan).  Clin Cancer 
Res. 2105 [Published OnlineFirst Jun 23, 2015; DOI: 10.1158/1078-0432.CCR-15-0670]. 
Shih LB, Xuan H, Aninipot R, Stein R, Goldenberg DM. In vitro and in vivo reactivity of an 
internalizing antibody, RS7, with human breast cancer. Cancer Res. 1995;55:5857s-63s. 
Starodub AN, Ocean AJ, Shah MA et al., First in human trial of a novel anti-trop-2 antibody-SN-
38 conjugate, sacituzumab govitecan, for the treatment of diverse metastatic tumors.  Clin 
Cancer Res. 2015;21(17):3870-8. 
Stein R, Basu A, Goldenberg DM, Lloyd KO, Mattes MJ. Characterization of cluster 13: the 
epithelial/carcinoma antigen recognized by MAb RS7. Int J Cancer Suppl. 1994;8:98-102. 
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Stein R, Basu A, Chen S, Shih LB, Goldenberg DM. Specificity and properties of MAb RS7-
3G11 and the antigen defined by this pancarcinoma monoclonal antibody. Int J Cancer. 
1993;55:938-46. 
Stein R, Goldenberg DM, Thorpe SR, Basu A, Mattes MJ. Effects of radiolabeling monoclonal 
antibodies with a residualizing iodine radiolabel on the accretion of radioisotope in tumors. 
Cancer Res. 1995;55:3132-9. 
Stein R, Goldenberg DM, Thorpe SR, Mattes MJ. Advantage of a residualizing iodine radiolabel 
for radioimmunotherapy of xenografts of human non-small-cell carcinoma of the lung. J Nucl 
Med. 1997;38:391-5. 
Trerotola M, Rathore S, Goel HL, et al. CD133, Trop-2 and alpha2beta1 integrin surface 
receptors as markers of putative human prostate cancer stem cells. Am J Transl Res. 2010;2:135-
44. 
Wolff AC, Hammond MEH, Hicks DG, et al. Recommendations for human epidermal growth 
factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of  
American Pathologists clinical practice guideline update.  J Clin Oncol. 2013;31:3997-4013.   
Zaanan A, Gauthier M, Malka D, et al. Second-line chemotherapy with fluorouracil, leucovorin, 
and irinotecan (FOLFIRI regimen) in patients with advanced small bowel adenocarcinoma after 
failure of first-line platinum-based chemotherapy: a multicenter AGEO study. Cancer. 
2011;117:1422-8. 
 
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APPENDIX 1. LIST OF STANDARD TREATMENTS FOR TNBC 
Refractory to or relapsed after at least two chemotherapy regimens containing one or more of the 
following agents: Doxorubicin, Epirubicin, Pegylated liposomal Doxorubicin, Docetaxel, 
Paclitaxel, Albumin-bound Paclitaxel (Abraxane), Gemcitabine, Vinorelbine, Vinblastine, 
Capecitabine, Ixabepilone (Ixempra) Eribulin, Platinum and TDM-1.  
 
  
 
  
 
Note:  The list includes regimens recommended by the NCCN guidelines as well as used in 
documented clinical trials.  Patients who received other treatment combinations may also be 
eligible for enrollment after obtaining approval from the medical monitor.   
 
 
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APPENDIX 2. PERFORMANCE STATUS EVALUATION 
by the Eastern Cooperative Oncology Group, PPD 
, Group Chair.* 
--------
GRADE 
ECOG PERFORMANCESTATUS 
0 
Fully active, able to can y on all pre-disease perfonnance without restriction 
1 
Restricted in physically strenuous activity but ambulato1y and able to cany out work 
of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulato1y and capable of all selfcare but unable to cany out any work activities; up 
and about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled; cannot can y on any selfcare; totally confined to bed or chair 
5 
Dead 
*Oken M, Creech R, To1mey D, et al. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 1982;5:649-655. 
ECOGPERFORMANCE STATUS 
KARNOFSKY PERFORMANCE STATUS 
100-Noimal, no complaints; no evidence of 
0- Fully active, able to cany on all pre-
disease 
disease perfo1mance without restriction 
90-Able to cany on nonnal activity; minor signs 
or symptoms of disease 
I- Restricted in physically strenuous 
80-Noimal activity with eff01t, some signs or 
activity but ambulato1y and able to cany 
symptoms of disease 
out work of a light or sedentaiy nature, e.g., 70-Cai·es for self but unable to cai1y on nonnal 
light house work, office work 
activity or to do active work 
2- Ambulatoiy and capable of all selfcai·e 
60-Requires occasional assistance but is able to 
but unable to cai1y out any work activities; 
cai·e for most of personal needs 
up and about more than 50% of waking 
SO-Requires considerable assistance and frequent 
hours 
medical cai·e 
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3—Capable of only limited selfcare; 
confined to bed or chair more than 50% of 
waking hours 
40—Disabled; requires special care and assistance 
30—Severely disabled; hospitalization is indicated 
although death not imminent 
4—Completely disabled; cannot carry on 
any selfcare; totally confined to bed or chair 
20—Very ill; hospitalization and active supportive 
care necessary 
10—Moribund 
5—Dead 
0—Dead 
*Karnofsky D, Burchenal J, The clinical evaluation of chemotherapeutic agents in cancer. In: 
MacLeod C, ed. Evaluation of Chemotherapeutic Agents. New York, NY: Columbia University 
Press; 1949:191–205. 
**Zubrod C, et al. Appraisal of methods for the study of chemotherapy in man: Comparative 
therapeutic trial of nitrogen mustard and thiophosphoramide. Journal of Chronic Diseases; 
1960:11:7-33. 
 
 
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APPENDIX 3. PROCEDURE FOR COLLECTION, STORAGE, AND 
SHIPMENT OF SAMPLES 
Instructions for collection, storage, and shipping of samples to be provided in a separate 
laboratory instruction manual prepared for this study.  Samples being referred to are as 
follows: 
 Serum samples for exposure response and anti-drug antibodies 
 Whole-blood samples for UGT1A1 genotyping 
 
 
 
 
 
 
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APPENDIX 4. STUDY CALENDAR 
PRETREATMENT 
TREATMENT*t 
POST 
TREATMENT 
~8 days 
IMMU-13 2 or TPC cycles to continue until 
Final 
Long 
Study Procedures 
ofClDl 
disease progression waffanting 
Visittt 
Tenn 
discontinuation or unacceptable toxicitv 
Follow-up 
:izned 
.to 11 iC lS 
Pa ie1 .t Eligib 'litv 
His o ,izv1 
IMMU-132 Only 
X 
UGTJAJ Genotype 
BRCA 1&2 Status, if available 
X 
Creatinine clearance 
X 
MRI Brain if known brain 
X 
Every 6 weeks through 36 weeks (week 6, 
metastasis 
12, 18, 24, 30, 36), then every 9 weeks 
reoc 1· 1g 
l s1 dv v'si 
Conco 1ita 
iica ions 
l s1 dv v'si 
Vital Signs4 
Each Infusion (IV) or study visit ( oral) 
X 
CBC (with platelets and WBC 
Every cycle: Day 1 & 8 (IMMU-132), 
diff. in absolute cell counts)5 
X 
each infusion (IV TPCs), or 
X 
Day 1, then per SOC ( oral TPC) 
ECOG Perfonnance Status 
X 
Every cycle: Day 1 
X 
Quality of Life6 
X 
Every cycle: Day 1 
X 
Every cycle: Day 1 & 8 (IMMU-132), 
Sernm Chemistries7 
X 
each infusion (IV TPCs), or 
X 
Day 1, then per SOC ( oral TPC) 
Hepatitis 
B 
surface 
antigen test, hepatitis C 
X 
antibody test 
Pregnancy Test, if applicable8 
X 
Even cycles: Day 1 
X 
Gemcitabine:dav 1 of everv cvcle 
Phvsica E a1 
1a 
] 
v ,rv cvi e: av 1 
U1 · .1alvsis 
Eve 1 :vd s: Dav 1 
12-lead ECG 
X 
Even cycles: Day 1 
X 
IMMU-132 only9 
• Exposure-Response10 
First cycle: Day 1 & 8 
See Schedule 
• Anti-Drng Antibodies12 
X 
Even cycles: Day 1 and Day 8 
X 
CT/MRI13 
X 
Every 6 weeks through 36 weeks (week 6, 
x13 bis 
12, 18, 24, 30, 36), then every 9 weeks 
Survival Status, Post-Study 
X 
Therapy14 
*IMMU-132 administered at dose of 10 mg/kg IV on day 1 & 8 of 21-day cycles; TPC dose and dosing cycles as 
per NCCN guidelines 
tFor TPC agents dosed weekly (e.g. vineorelbine), a cycle is defined as eve1y 3 weeks (21 days) 
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†† Last study visit 4 weeks after the last treatment dose or in event of premature study termination.  
1Documented confirmation of TNBC diagnosis 
2Treatment history to include treatment response and also time to progression for last therapy regimen. 
 
 
 
4Vital signs (heart rate, systolic and diastolic blood pressure, respiratory rate, and body temperature) for patients 
receiving IMMU-132 required on Day 1 of cycle 1 prior to infusion, during infusion every 15 minutes for the first 
hour then every 30 minutes, at completion, and then additionally 30 minutes later. In absence of significant changes, 
may be reduced with subsequent doses to prior to infusion, at 30 minutes, and then at completion. For patients 
receiving TPC, required prior to, once during, and at the end of each infusion, (Vinorelbine vital signs are required 
prior to and at the end of each infusion due to short infusion time) or if administered orally, once at each study visit; 
otherwise as per local standard of care. Vital signs are required in all patients at final study visit. Timepoints can be 
± 1-2 min. 
5 To be repeated within 72 hours of cycle 1, day 1 to confirm eligibility. CBC for patients receiving IMMU-132, 
required at baseline, Day 1 & 8 of each cycle, and final study visit. For patients receiving TPC, required at baseline, 
Day 1 of each cycle, and final study visit, and as required by SOC on other treatment days or other study visits.  
Note, is not required to be repeated at C1D1 (IMMU-132 and TPC) if baseline sample collected within 72 hours 
prior).  In the event of ≥ Grade 3 hematological toxicity, CBC will be obtained more frequently at the discretion of 
the managing physician until toxicity recovers to Grade 2 levels and then weekly until recovery to baseline or Grade 
1 levels. 
6QOL (EORTC QLQ C30) questionnaire to be completed by all patients at baseline, on Day 1 of each cycle, and at 
final study visit.   
7Serum chemistries include glucose, creatinine, BUN, total bilirubin, AST, ALT, LDH, alkaline phosphatase, serum 
albumin, total protein, Na, K, calcium, Cl, CO2, magnesium and phosphate.  Serum chemistries are required in all 
patients at baseline, Day 1 of every cycle (not required to be repeated at C1D1 if baseline sample collected within 72 
hours prior), and final study visit. To be obtained more frequently at the discretion of the managing physician if 
abnormal results warrant follow-up 
8Pregnancy test required in patients (if applicable) within 7 days prior to start of treatment, Day 1 of even cycles (2, 
4, 6, 8, etc.), and final study visit.  For patients receiving Gemcitabine, pregnancy test will be performed on day 1 of 
every cycles (every four weeks). 
9Serum samples to be frozen immediately and stored for shipment to the Sponsor’s designee to perform the assays.  
10Serum samples for exposure-response required from all patients receiving IMMU-132, prior to infusion and 30 
minutes afterwards on both Days 1 and 8 of Cycle 1 only.  
 
 
 
 
 
12Anti-drug antibodies required from all patients receiving IMMU-132 with serum samples obtained at baseline 
(may be taken at C1D1 provided it is before study drug administration), at Day 1 of even cycles, and at final study 
visit.   
13CT or MRI (chest, abdomen, pelvis; other if needed) is required in all patients after the start of treatment at 6-week 
intervals through 36 weeks, then every 9 weeks until the occurrence of progression of disease requiring 
discontinuation of further treatment. For each patient, the same imaging technique should be used throughout the 
trial.  Responses identified prior to 36 weeks on study require confirmatory scans, which will be performed at the 
next scheduled scanning time-point (6 weeks later). For responses after 36 weeks, confirmatory scans will be done 
within 6 weeks of scan showing the onset of response.  Additional CT/MRI can be performed at the discretion of the 
physician to assess disease status as medically indicated.  Clinical progression leading to patient discontinuation 
should be documented also by CT or MRI scan of target lesions if possible.  Patients who discontinue treatment due 
to toxicity will continue with radiologic response assessments at the protocol-required schedule, until progression of 
disease or initiation of new therapy.   
13 bis: if PD not yet confirmed 
14All patients will be followed every 4 weeks thereafter for survival, which may be by telephone and will include 
documentation of any further therapy administrated for their breast cancer. 
 
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CCI-
-


Immunomedics, Inc. 
IMMU-132-05 
 
Sacituzumab Govitecan 
 
26 August 2019 
CONFIDENTIAL 
Page 102 
 
NOTE: Unless otherwise specified, collection windows for study time points are within ± 2 
days for the treatment schedule and ± 5 business days for response assessments. Planned 
deviations in treatment schedule are allowable up to 7 days due to holidays, vacation or 
personal reasons. 
 
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APPENDIX 5. EORTC QLQ-C30 (VERSION 3) 
We are interested in some things about you and your health. Please answer all of the questions 
yourself by circling the number that best applies to you. There are no "right" or "wrong" answers. 
The info1mation that you provide will remain strictly confidential. 
Please fill in your initials: 
Your bi11:hdate (Day, Month, Year): 
Today's date (Day, Month, Year): 
Not at 
A 
Quite 
Very 
All 
Little 
a Bit 
Much 
1. 
Do you have any trouble doing strenuous activities, 
like canying a heavy shopping bag or a suitcase? 
1 
2 
3 
4 
2. 
Do you have any trouble taking a long walk? 
1 
2 
3 
4 
3. 
Do you have any trouble taking a sho11 walk outside of the house? 
1 
2 
3 
4 
4. 
Do you need to stay in bed or a chair dming the day? 
1 
2 
3 
4 
5. 
Do you need help with eating, dressing, washing 
yourself or using the toilet? 
1 
2 
3 
4 
During the past week: 
6. 
Were you limited in doing either your work or other daily activities? 
1 
2 
3 
4 
7. 
Were you limited in pursuing your hobbies or other 
leisure time activities? 
1 
2 
3 
4 
8. 
Were you sholi of breath? 
1 
2 
3 
4 
9. 
Have you had pain? 
1 
2 
3 
4 
10. Did you need to rest? 
1 
2 
3 
4 
11. Have you had trouble sleeping? 
1 
2 
3 
4 
12. Have you felt weak? 
1 
2 
3 
4 
13. Have you lacked appetite? 
1 
2 
3 
4 
14. Have you felt nauseated? 
1 
2 
3 
4 
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IMMU-132-05 
 
Sacituzumab Govitecan 
 
26 August 2019 
CONFIDENTIAL 
Page 104 
 
 
15. Have you vomited? 
1 
2 
3 
4 
 
16. Have you been constipated? 
1 
2 
3 
4 
 
17. Have you had diarrhea? 
1 
2 
3 
4 
 
18. Were you tired? 
1 
2 
3 
4 
 
19. Did pain interfere with your daily activities? 
1 
2 
3 
4 
 
20. Have you had difficulty in concentrating on things, 
 
like reading a newspaper or watching television? 
1 
2 
3 
4 
 
21. Did you feel tense? 
1 
2 
3 
4 
 
22. Did you worry? 
1 
2 
3 
4 
 
23. Did you feel irritable? 
1 
2 
3 
4 
 
24. Did you feel depressed? 
1 
2 
3 
4 
 
25. Have you had difficulty remembering things? 
1 
2 
3 
4 
 
26. Has your physical condition or medical treatment 
 
interfered with your family life? 
1 
2 
3 
4 
 
27. Has your physical condition or medical treatment 
 
interfered with your social activities? 
1 
2 
3 
4 
 
28. Has your physical condition or medical treatment 
 
caused you financial difficulties? 
1 
2 
3 
4 
 
 
For the following questions please circle the number between 1 and 7 that  
best applies to you 
 
29. How would you rate your overall health during the past week? 
 
 
 1 
2 
3 
4 
5 
6 
7 
 Very poor 
 
 
 
 
 
Excellent 
 
30. How would you rate your overall quality of life during the past week? 
 
 1 
2 
3 
4 
5 
6 
7 
 Very poor 
 
 
 
 
 
Excellent 
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IMMU-132-05 
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APPENDIX 6. RESPONSE EVALUATION CRITERIA IN SOLID 
TUMORS (RECIST) 1.1 
New Response evaluation criteria in Solid tumors: Revised RECIST criteria [EJC 4 (2): 228-247, 
2009] are summarized below. 
Measurable/Non-Measurable Lesions. Each tumor lesion or site of disease identified at 
baseline is categorized as either a measurable lesion or a non-measurable lesion according to the 
following definitions. 
Lesion Type 
Measurable 
Non-Measurable 
Qualifyine Definition 
Tumor lesions: Must be accurately measured in at least one dimension 
(longest diameter in the plane of measurement is to be recorded) with a 
minimum size of: • 10mm by CT scan (CT scan slice thickness no greater 
than 5 mm.) • 10mm caliper measurement by clinical exam (lesions which 
cannot be accurately measured with calipers should be recorded as non-
measurable) • 20mm by chest X-ray. 
Malignant lymph nodes: To be considered pathologically enlarged and 
measurable, a lymph node must be 15mm in sho1i axis when assessed by CT 
scan (CT scan slice thickness recommended to be no greater than 5 mm). At 
baseline and in follow-up, only the sho1i axis will be measured and followed. 
All other lesions, including small lesions (longest diameter < 10mm or 
pathological lymph nodes with 10 to < 15mm sho1i axis) as well as tiuly 
non-measurable lesions. Lesions considered tiuly non-measurable include: 
leptomeningeal disease, ascites, pleural or pericardial effusion, inflammato1y 
breast disease, lymphangitic involvement of skin or lung, abdominal 
masses/abdominal organomegaly identified by physical exam that is not 
measurable by reproducible imaging techniques. 
Special considerations regarding lesion measurability: 
Bone lesions, cystic lesions, and lesions previously ti·eated with local therapy require paiiicular 
comment: Bone lesions: • Bone scan, PET scan or plain films ai·e not considered adequate 
imaging techniques to measure bone lesions. However, these techniques can be used to confnm 
the presence or disappeai·ance of bone lesions. • Lytic bone lesions or mixed lytic-blastic lesions, 
with identifiable soft tissue components, that can be evaluated by cross sectional imaging 
techniques such as CT or MRI can be considered as measurable lesions if the soft tissue 
component meets the definition of measurability described above. 
Blastic bone lesions are non-measurable. Cystic lesions: • Lesions that meet the criteria for 
radiographically defined simple cysts should not be considered as malignant lesions (neither 
measurable nor non-measurable) since they are, by definition, simple cysts. • 'Cystic lesions' 
thought to represent cystic metastases can be considered as measurable lesions, if they meet the 
definition of measurability described above. However, if non-cystic lesions ai·e present in the 
same patient, these ai·e prefen ed for selection as target lesions. 
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Lesions with prior local treatment: Tumor lesions situated in a previously i1Tadiated area, or in 
an area subjected to other loco-regional therapy, are usually not considered measurable unless 
there has been demonstrated progression in the lesion. All measurements should be recorded in 
metric notation, using calipers if clinically assessed. All baseline evaluations should be 
perfonned as close as possible to the treatment start and never more than 28 days before the 
beginning of the treatment. 
Target Lesions. Target lesions are selected from measurable lesions at baseline on the basis of 
their size and suitability for accurate repeated measurements by imaging techniques or clinical 
judgment. The sum of the longest diameter (LD) for all target lesions provides a quantitative 
means of characterizing objective tumor response to treatment as follows: 
Evaluation Criteria Used for Cateeorizine Treatment Response of Tare.et Lesions 
Response Cate2ory 
Definition 
Complete Response 
Disappearance of all target lesions 
(CR) 
Paiiial Response (PR) > 30% decrease in the sum of the longest diaineter (LD) of target 
lesions, taking as reference the baseline sum LD 
Progressive Disease 
> 20% increase in the sum of the LD of tai·get lesions, taking as 
reference the smallest sum LD recorded since the treatment staii ed or 
(PD) 
the appearance of one or more new lesions. 
Stable Disease 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
(SD) 
qualify for PD, taking as reference the smallest sum LD since the 
treatment staii ed 
Non-Target Lesions. Non-tai·get lesions are other lesions (or sites of disease) not identified as 
target lesions at baseline. These include both non-measurable lesions as well as measurable 
lesions exceeding the maximum number allowed per organ or in total. The response of non-
target lesions to treatment is evaluated on the basis of their presence or absence as follows: 
Evaluation Criteria Used for Cateeorizine Treatment Response of Non-Tarnet Lesions 
Response Cate2ory 
Definition 
Complete Response (CR) 
Disappearance of all non-tai·get lesions and nonnalization 
tumor mai·ker levels initially above upper liinits of nonnal 
of 
Progressive Disease (PD) 
Appearance of one or more new lesions and/or unequivocal 
progression of existing non-tai·get lesions 
fucomplete Response/Stable 
Persistence of one or more non-target lesion(s) or/and 
Disease (SD) 
maintenance of tumor mai·ker level above the normal limits 
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New Lesions. New lesions not present at baseline should be recorded at time of occmTence. 
Overall Response. The overall response is the best response recorded from the staii of the 
treatment until disease progression/recmTence (taking as reference for progressive disease the 
smallest measurements recorded since the ti·eatment staiied). To be assigned a status of PR or 
CR, changes in tumor measurements must be confnmed by repeat assessments that should be 
perfonned 4 weeks after the criteria for response are first met. In the case of SD, follow-up 
measurements must have met the SD criteria at least once with a minimum inte1val of at least 6-8 
weeks from randomization. 
Target Lesions 
CR 
CR 
PR 
SD 
PD 
Any 
Any 
Non-tai·get Lesions 
CR 
Incomplete 
response/SD 
Non-PD 
Non-PD 
Any 
PD 
Any 
New Lesions 
Overall Response 
No 
CR* 
No 
PR 
No 
PR 
No 
SD 
Yes or No 
PD** 
Yes or No 
PD** 
Yes 
PD** 
*When evaluation of possible CR depends on distinguishing residual disease from normal tissue, fine needle 
aspirate/biopsy is reconunended before confinning the complete response status. 
**Patients v.iithout objective evidence of disease progression, but with globally deteriorated health status requiring 
discontinuation of treatment should be classified as having "symptomatic deterioration" at that time, with every 
effort made to document the objective progression, even after discontinuation of treatment. 
Duration of Response. The duration of overall response is measured from the time 
measurement criteria are met for CR or PR (whichever is first recorded) until the first date that 
recurrent or progressive disease is objectively documented (taking as reference for progressive 
disease the smallest measurements recorded since the ti·eatment sta1ied). Stable disease is 
measured from the strut of the ti·eatment until the criteria for progression are met, taking as 
reference the smallest measurements recorded since the ti·eatment staiied. 
26 August 2019 
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IMMU-132-05 
 
Sacituzumab Govitecan 
 
26 August 2019 
CONFIDENTIAL 
Page 108 
 
APPENDIX 7. CHILD-PUGH SCORE IN PATIENTS WITH HEPATIC 
IMPAIRMENT  
 
Table adapted from Superfin D, Iannucci AA, Davies AM. Commentary: Oncologic drugs in patients with organ 
dysfunction: A summary. The Oncologist 2007;12:1070-1083.  
 
Modified Child-Pugh Score 
Manifestation 
One point 
Two points 
Three points 
Encephalopathya 
None 
Grade I–II 
Grade III–IV 
Ascites 
Absent 
Nontense 
Tense 
Bilirubin (mg/dl)  
     Noncholestatic   
     Cholestatic    
 
<2 
<4 
 
2–3 
4–10 
 
>3 
>10 
Albumin (g/dl) 
>3.5 
2.8–3.5 
<2.8 
INR (International normalized ratio) 
<1.7 
1.7–2.3 
>2.3 
aEncephalopathy: I, mild confusion or slowing, no asterixis; II, drowsy, asterixis present; III, 
marked confusion, somnolence, asterixis present; IV, unresponsive or responsive only to painful 
stimuli, no asterixis.  
Class A, 5– 6 points 
Class B, 7–9 points 
Class C, >10 points 
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