Clinical trial NCT01631552
Conditions: Gastric Adenocarcinoma Esophageal Cancer Hepatocellular Carcinoma Non-small Cell Lung Cancer Small Cell Lung Cancer Ovarian Epithelial Cancer Carcinoma Breast Stage IV Hormone-refractory Prostate Cancer Head and Neck Cancers- Squamous Cell Renal Cell Cancer Urinary Bladder Neoplasms Cervical Cancer Endometrial Cancer Glioblastoma Multiforme Triple Negative Breast Cancer Pancreatic Cancer
Sponsor: Gilead Sciences
Start date: 2012-12-17; Completion date: 2020-08-13
Enrollment: 515 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The primary objective in Phase I is to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent administered in 21-day treatment cycles in previously treated participants with advanced epithelial cancer. In Phase II, the primary objective is to evaluate the safety and efficacy of sacituzumab govitecan-hziy administered in 21-day treatment cycles at a dose selected in Phase I.

Tumor types in the study will include: cervical, colorectal, endometrial, ovarian, esophageal, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular, prostate, non-small-cell lung cancer, pancreatic, renal cell, small-cell lung cancer, non-triple negative breast cancer (non-TNBC), triple-negative breast cancer (TNBC) and metastatic urothelial cancer (mUC).

Detailed description:
The outcome measures are planned to be assessed up to the data cutoff date. Following the data cutoff date, the participants will either stay on the study and will be followed for safety data collection or rolled into another Gilead-sponsored study. Therefore, only safety data will be collected after the data cutoff date.

Arms: arm 1: Participants will receive sacituzumab govitecan-hziy (SG) 8 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. arm 2: Participants will receive SG 10 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. arm 3: Participants will receive SG 12 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. arm 4: Participants will receive SG 18 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.
Interventions: intervention 1: Sacituzumab Govitecan-hziy (SG)
Intervention descriptions: intervention 1: Administered via intravenous (IV) infusion

Protocol documents:
Prot_000.pdf: 
Product: IMMU-132 
Protocol: IMMU-132-01 
 
 
 
January 23, 2020 
CONFIDENTIAL 
Page 1 of 79 
 
IMMUNOMEDICS®, INC. 
 
 
 
 
 
PROTOCOL: IMMU-132-01 
 
 
Phase I/II Study of IMMU-132 in 
Epithelial Cancers 
 
 
 
 
 
Protocol Title: 
A Phase I/II Study of IMMU-132 (hRS7-SN38 Antibody Drug Conjugate) 
in Patients with Epithelial Cancer 
 
 
 
IND #: 
115621 
 
 
 
Sponsor: 
Immunomedics, Inc. 
300 The American Road 
Morris Plains, NJ  07950 
 
 
 
 
 
 
 
 
 
Release Date:      May 30, 2012 
 
Revision Date:    January 23, 2020  
(Includes Amendments #1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, & 13) 
 
 
 
 
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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SYNOPSIS            
 
Protocol Number 
IMMU-132-01 
 
 
Protocol Title 
A Phase I/II Study of IMMU-132 (hRS7-SN38 Antibody Drug Conjugate) in 
Patients with Epithelial Cancer 
Study Drug                IMMU-132 (hRS7-SN38 antibody-drug conjugate) is provided in glass vials as a 
sterile lyophilized powder 
 
 
Objectives 
In Phase I, the primary objective 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. In Phase II, the primary 
objective is the evaluation of the safety and efficacy of IMMU-132 administered 
in 3-week treatment cycles at a dose selected in Phase I, while the secondary 
objectives include pharmacokinetics and immunogenicity. 
Scope of Study       
This is planned as a multi-center study.  In Phase II, up to 150 patients 
(assessable) in each of 5 cancer subtypes [triple-negative and non-triple-negative 
breast cancer (TNBC, non-TNBC), non-small-cell lung cancer (NSCLC), small 
cell lung cancer (SCLC), urothelial cancer (UC)] and up to 56 patients 
(assessable) per other cancer types will be studied at the 10 mg/kg dose. 
Study Duration        In Phase II, all patients receive IMMU-132 10 mg/kg administered once-weekly 
for the first 2 weeks of 3-week treatment cycles, to be continued in the absence of 
unacceptable toxicity or progression of disease requiring termination of further 
treatment.  Patients who have progression of disease assessed for the first time 
during the study but derive continued clinical benefit from IMMU-132 treatment, 
may continue to be treated based on physician discretion (with Sponsor 
approval).  After discontinuing treatment, follow-up is then required until 
resolution or stabilization of any treatment-related toxicity, and patients with 
stable disease or objective responses must also continue evaluations for up to 2 
years or until progression of disease or initiation of other treatment. All patients 
will be followed for survival every month, which may be by telephone, but no 
longer than 2 years from final study evaluation. 
Background      
SN-38 is the active metabolite of irinotecan (CPT-11), a highly potent 
chemotherapeutic agent that is approved as a single agent and is incorporated into 
combination regimens for the treatment of advanced colorectal cancer, but which 
has dose-limiting gastrointestinal and hematologic toxicities.  hRS7 is a 
humanized monoclonal antibody which targets the Trop-2 (human trophoblast 
cell-surface antigen) antigen which is expressed on a variety of human 
carcinomas and also known as EGP-1 (epithelial glycoprotein-1), GA733-1 
(gastric antigen 733-1), and TACSTD2 (tumor-associated calcium signal 
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transducer). Trop-2 has been associated with more aggressive disease in some 
cancers and is a promising target for drug delivery with hRS7, since a portion of 
the antibody internalizes when bound to the antigen on the cell surface.  As such, 
Immunomedics has developed an antibody-drug conjugate (ADC), called 
IMMU-132, in which SN-38 is conjugated to hRS7 in order to enhance delivery 
of SN-38 to Trop-2-expressing tumors while reducing systemic toxicity. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Based upon data from the Phase I portion of this study, a starting dose of 8 or 10 
mg/kg, administered on days 1 and 8 of a 21-day cycle was considered 
acceptable for further evaluation, and 10 mg/kg was subsequently selected for the 
ongoing Phase II portion of this study.  Severe (Grade 3 or higher) toxicities have 
primarily been limited to neutropenia, diarrhea or febrile neutropenia (see 
Investigator’s Brochure for most recently updated safety profile).  
In Phase I & Phase II, there was evidence of efficacy. Partial responses have been 
observed currently in patients with triple-negative breast cancer, small-cell lung 
cancer, non-small cell lung cancer, esophageal cancer and urinary bladder and 
colorectal cancers. Disease stabilization has been observed in many patients. 
Many patients have continued therapy for periods of months, but with little 
evidence of evoking antibodies to the drug (SN-38) or antibody (hRS7) of the 
ADC. 
Study Design              This is a Phase I/II, open-label study of IMMU-132 in previously treated patients 
with advanced epithelial cancers, including ovarian, endometrial, cervical, breast 
(TNBC and non-TNBC), prostate (hormone refractory), lung (non-small-cell and 
small-cell), head & neck (squamous cell), esophageal, gastric, hepatocellular, 
renal (clear cell), papillary thyroid, and  urothelial cancers, as well as 
glioblastoma multiforme.  A table of approved or standard or commonly used 
therapeutic regimens for each of these cancer types is included in Appendix 1.  
Patients who have not received approved or standard treatment lines for their 
cancer must be informed that alternatives to receiving IMMU-132 are available 
prior to their consenting to participate in this trial. 
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In Phase II, up to 150 patients (assessable) in each of 5 cancer subtypes (TNBC, 
non-TNBC, NSCLC, SCLC, UC) and up to 56 patients (assessable) per other 
cancer types will be studied at 10 mg/kg dose. 
 
Baseline evaluations within 4 weeks of the scheduled start of treatment include 
patient history, physical examination with vital signs and performance 
evaluation, local histology review to confirm one of the epithelial cancers 
included, contrast-enhanced CT or MRI scans (chest, abdomen, pelvis with 
additional imaging of other involved areas), CBC (with differential and platelet 
count), routine serum chemistries, urinalysis (with microscopic, if needed), 
PT/PTT, EKG, and serum samples for human anti-human antibody (HAHA).  
 
 
 
 
 
 
 
 
 
 
Tumor biomarkers are to be monitored at baseline and at each radiologic 
response assessment time point whenever possible. 
  
 
 
 
 
 
 
A single whole-blood sample (purple- or pink-topped tube, 2 mL) will be 
collected from each registered patient prior to receiving IMMU-132 for 
determination of UGT1A1 and related genotypes.  This sample will be shipped to 
Sponsor who will perform this assay.  The results from this test are NOT required 
to determine eligibility but will be used retrospectively to assess its utility in 
predicting toxicity. 
 
 
 
 
 Core biopsies that are 
fresh-frozen and also formalin-fixed (described above) are also desired at 
baseline and intervals during therapy whenever possible. 
 
In the ongoing Phase II study, all patients receive IMMU-132 10 mg/kg 
administered in 3-week treatment cycles with weekly dosing the first two weeks 
(days 1 and 8 of 21-day cycles) and no dosing the third week. The cycles are to 
be continued in the absence of unacceptable toxicity or progression of disease 
requiring termination of further treatment.  The first assessment of disease 
progression per RECIST1.1 does not require discontinuation of study treatment if 
there is still the potential for patient benefit in the opinion of the investigator and 
approved by the Sponsor, but treatment must be discontinued if subsequent 
imaging documents disease progression from that assessment.    
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All patients are closely monitored over the course of their treatment, and NCI 
CTCAE v4.0 is used to grade all adverse events and to provide dose reduction, 
delay or cessation guidelines in the event of treatment-related toxicity.  Based on 
irinotecan and animal testing, the major toxicity of IMMU-132 is expected to be 
gastrointestinal symptoms and hematologic suppression. Growth factors and 
other supportive care are allowed when medically necessary any time during 
treatment with IMMU-132 but should not be given prophylactically before start 
of treatment with IMMU-132 first dose in cycle 1. 
 
In the current experience in over 200 patients, the major Grade 3 or Grade 4 
toxicity has been neutropenia, which is managed with dose delay, dose reduction, 
or growth factors, if spontaneous remission is not experienced within 7 days. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
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Patients who exhibit an excessive cholinergic response to IMMU-132 treatment 
(e.g., abdominal cramping, diarrhea, salivation, etc.) can receive appropriate 
premedication (e.g., atropine) for subsequent treatments. 
Because of the many clinical sites participating in this trial, the investigators are 
requested not to consent and start screening a potentially eligible patient before 
consulting with the Sponsor to determine when such a patient could be accepted 
into the trial, should the patient prove to be eligible after screening. 
  
Study procedures during treatment include physical examination and vital signs, 
CBC (with differential and platelet count), routine serum chemistries, PT/PTT, 
serum samples for PK (to be collected in all patients in Phase II, unless exempted 
by the Sponsor) and HAHA, concomitant medications and adverse events, and 
EKG.  Starting with the initial dose of IMMU-132, CT or MRI examinations and 
biomarkers are to be obtained every 8 weeks until the occurrence of progression 
of disease requiring termination of further treatment.   At that time, the patient 
will undergo an end-of-study evaluation, with additional follow up only required 
until resolution or stabilization of any treatment-related toxicity. For scans 
showing stable disease, but with substantial or rapid tumor shrinkage near 
threshold for a partial response, the 8-week interval for the next scan may be 
shortened at investigator discretion and if discussed with the medical monitor.  
Confirmatory CT/MRI scans are to be obtained 4 to 6 weeks after an initial 
partial response and/or 4 to 6 weeks after an initial complete response. If a 
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confirmatory scan is performed, the subsequent scans will be scheduled every 8 
weeks from the confirmatory scan.  Additional scans may be performed at the 
discretion of the physician to assess disease status as medically indicated. At the 
discretion of treating physician, patients who have biopsiable lesion(s) and 
consented to biopsy(ies) will provide during the study as many tumor metastasis 
core biopsy samples as possible, 
 
 In addition, SN-38 concentrations will be 
determined only in specimens that are taken within one day after completion of 
any IMMU-132 infusion. All specimens should be placed in 10% formalin, 
without any further processing and shipped to sponsor for analysis, as well as 
fresh-frozen specimens for determining protein or RNA levels. 
 
In the event of treatment termination due to unacceptable toxicity, the patient will 
continue on study follow up until there is documentation of progression of 
disease, at which time an end-of-study evaluation will be performed, with 
additional follow-up only required until resolution or stabilization of any 
treatment-related toxicity. 
Long-term follow-up will continue in patients with stable disease or an objective 
response with evaluations performed every 3 months for up to 2 years or until 
progression of disease or initiation of other treatment.  All patients will be 
followed for survival every month, which may be by telephone, but no longer 
than 2 years from final study evaluation. 
 
Patients continuing to benefit from treatment at time of study closure may be 
eligible to enroll in a rollover study, so they may continue to receive treatment. 
 
(See study calendar below for detailed schedule of procedures) 
Population              
Males or non-pregnant, non-lactating females ≥ 18 years of age, able to give 
signed, written informed consent, may be eligible if they have documented 
epithelial cancer that involves any of the following tumor types: ovarian, 
cervical, endometrial, breast (triple-negative and other breast tumors), prostate 
(hormone refractory), lung (non-small-cell and small-cell), head and neck 
(squamous cell), esophageal, colorectal, gastric, pancreas, renal (clear cell), 
papillary thyroid, glioblastoma multiforme, urinary bladder (urothelial), and 
hepatocellular. Patients must have metastatic disease (except GBM) and have 
either relapsed after receiving or were refractory to at least one standard 
chemotherapy (or biological, targeted or hormonal) regimen for their disease.  
 
 
 
 
 
 
 
  
                                    
 
 
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. 
 
All patients must have measurable disease by CT or MRI at the time of 
treatment, but no single lesion ≥ 7 cm in diameter. Patients with any bulky 
lesions over 7 cm, but otherwise eligible, may be considered for enrollment 
after discussion and approval by the medical monitor (Sponsor). Patients who 
have not received all approved or standard treatment lines for their cancer must 
be informed that these alternatives to receiving IMMU-132 are available prior 
to consenting to participate in this trial.  Patients must be 2 weeks beyond any 
major surgery, radiation, immunotherapy, endocrine therapy, investigational 
drugs including small molecular inhibitors, or chemotherapy regimens, and 
have recovered from any acute toxicities associated with these prior 
treatment(s) to Grade 1 or less (except alopecia). 
Patients must have a life expectancy ≥ 6 months, an ECOG performance score  
of  0  or  1,  adequate  hematology  without  ongoing  transfusional support 
(ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin > 9 g/dL), no active 
≥ Grade 2 anorexia, nausea or vomiting or signs of intestinal obstruction, no 
prior history of clinically significant bleeding, intestinal obstruction, or GI 
perforation within 6 months, no known history of anaphylactic reaction or ≥ 
Grade 3 GI toxicity to prior irinotecan, no known history of unstable angina, 
MI, or CHF present within 6 months or clinically  significant  cardiac  
arrhythmia  (other  than  stable  atrial fibrillation) requiring anti-arrhythmia 
therapy, no known history of clinically significant, active COPD, or other 
moderate to severe chronic respiratory illness present within 6 months, 
adequate renal (creatinine ≤2.0 x IULN) and hepatic function (bilirubin ≤1.5 x 
IULN, AST and ALT ≤ 3 x IULN or 5 x IULN if known liver metastases), and 
with otherwise all toxicity at study entry < Grade 1 by NCI CTC v4.0 (Patients 
with ≤ Grade 2 neuropathy will be eligible).  Patients with Gilbert’s disease are 
excluded.  Patients with treated, non-progressive brain metastases, off high-
dose steroids (>20 mg prednisone or equivalent) for at least 4 weeks, can be 
enrolled in the trial.  
 
Patients with successfully treated 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. 
 
Patients of childbearing potential must be willing to practice birth control 
during the study until at least 12 weeks after treatment, and women of 
childbearing potential must have a negative urine or serum pregnancy test to 
enter the study. 
 
Other exclusion criteria include patients known to be HIV positive, hepatitis 
B-antigen positive, or hepatitis C positive, infection requiring intravenous 
antibiotic use within 1 week, use of systemic, high-dose corticosteroids   
within 2 weeks, and 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. 
Concomitant 
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Medications 
Patients enrolled in this trial will be refractory to or relapsed after one or more 
chemotherapy regimens, including irinotecan in colorectal cancer patients, or 
hormonal agents, biologicals or targeted therapeutic agents, and may also have 
received antibody therapy. All of these treatments must be discontinued for a 
minimum of 2 weeks prior to starting IMMU-132, and these or other anti-cancer 
therapies (i.e., drugs, biologics, procedures) are not permitted during this study. 
Palliative and/or supportive medications and procedures are permitted to be used 
during the study. Patients who receive palliative and/or supportive medications 
and procedures should have a washout period of 1 week after the last IMMU-132 
dose and 2 weeks prior to resuming the treatment with next IMMU-132 dose, 
unless otherwise a different washout period is arranged by discussion with 
medical monitor (Sponsor). The requirement for premedication with 
acetaminophen, steroids, and diphenhydramine or equivalents is not anticipated; 
however, these will be employed as clinically indicated to decrease infusion 
reactions. 
 
Antiemetics, anti-diarrheal medications, cytokines or blood transfusions may be 
administered as clinically indicated. Cytokines or blood transfusions are not 
permitted prophylactically before start of first IMMU-132 dose in cycle 1. Other 
supportive care is allowed as medically warranted. 
Phase II                 
In Phase II, up to 150 patients (assessable) in each of 5 cancer subtypes 
(TNBC, non-TNBC, NSCLC, SCLC, UC) and up to 56 patients (assessable) 
per cancer type for all other cancers will be studied at the 10 mg/kg dose. 
Endpoints               
Safety and tolerability will be evaluated from adverse events, standard safety 
laboratories (CBC with differential and platelet count, serum chemistries, and 
urinalysis), physical examination, vital signs, and EKG. 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 CTCAEv4.0 toxicity grades.  Descriptive statistics will be 
used to characterize adverse events, cytopenias, and other abnormal laboratories. 
 
Efficacy will be evaluated from CT scans (or if needed MRI studies), using 
RECIST 1.1 criteria to classify tumor response, time to onset of objective 
response, duration of objective response, time to progression and survival. 
Changes in biomarkers will be evaluated. 
 
Pharmacokinetics (PK) will be evaluated from serum samples using an ELISA 
assay performed by the Sponsor. The results will be characterized by standard PK 
parameters including peak and trough values, area-under- the-curve (AUC), 
maximum concentration (Cmax), and half-life (T1/2), if feasible, and 
summarized using descriptive statistics. 
 
Immunogenicity will be determined from serum samples using an ELISA assay 
performed by the Sponsor for the occurrence of any human antibodies against 
IMMU-132 (e.g., HAHA).  The occurrences of any positive HAHA results will 
be characterized by descriptive statistics. 
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Long-Term 
Follow-Up 
After the last treatment dose, follow-up continues for patients who have not 
progressed with CT studies performed every 3 months for up to 2 years or until 
progression of disease or initiation of other treatment.  Follow-up is also required 
at least every 3 months until resolution or stabilization for any treatment-related 
abnormalities that warrant continued monitoring.  Adverse events and 
concomitant medications reported at any follow-up visits will include outcome of 
any ongoing unresolved events, new events attributed to the study treatment, 
deaths, hospitalizations, GI toxicity, and infectious episodes requiring 
prescription or IV anti-infectives.  All patients will be followed for survival every 
month, which may be by telephone with patient or caregiver, for no longer than 2 
years from final study evaluation. 
 
 
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Table 2: 
Study Calendar 
PRETREATMENT 
TREATMENT 
(3-Week Treatment Cycles) 
POST TREATMENT 
 
Within 4 
Wks of 
Entry 
Cycle 1 
Subsequent Cycles 
Final1 
Study 
Eval 
Long-Term   
Follow-up 
Every1month 
Day 
1 
Day 
8 
Day 
15 
Day 
1 
Day 
8 
Day 
15 
Signed Informed Consent 
X 
 
 
 
 
 
 
 
 
Patient Eligibility 
X 
 
 
 
 
 
 
 
 
Histology review 
X 
 
 
 
 
 
 
 
 
Pregnancy Test 
X3 
 
 
 
X3 
 
 
X 
 
Hepatitis B & C Test 
X 
 
 
 
 
 
 
 
 
Medical/Surgical History 
X 
 
 
 
 
 
 
 
 
UGT1A1 genotype 
 
X 
 
 
 
 
 
 
 
Genotype analysis results 13 
 
X 
 
 
 
 
 
 
 
CT/ MRI (chest, abdomen, pelvis; 
other if needed) and biomarkers4 
X 
 
 
X 
 
EKG 
X 
 
 
 
X10 
 
 
X 
X2 
Phys. Exam (PE) 
X 
 
 
 
X11 
 
 
X 
X2 
CBC (with diff, platelets)5 
X 
X 
X 
 
X 
X 
 
X 
X2 
Serum Chemistries5 
X 
X 
X 
 
X 
X 
 
X 
X2 
PT/PTT 
X 
 
 
 
X11 
 
 
 X11 
X2 
Urinalysis 
X 
 
 
 
X11 
 
 
X 
 
Concomitant Medications 
X 
X 
X 
 
X 
X 
 
X 
X6 
IMMU-132 infusion 
 
X 
X 
 
X 
X 
 
 
 
Vital Signs 
X 
X7 
X7 
 
X7 
X7 
 
X 
X2 
Adverse Event Reporting 
 
X 
X 
 
X 
X 
 
X 
      X8 
 Biopsy Tissue 
X
12 
 
 
 
 
 
 
 
 
Survival status 
 
 
 
 
 
 
 
 
X 
1 Performed 14 days after the last dose of study drug or in event of premature study termination  
2 Otherwise, long-term follow-up required every 3 months for up to 2 years or initiation of other treatment in patients who have not progressed, or only until resolution of 
any treatment-related abnormalities once patients progresses  
3 Pregnancy test, if applicable, will be performed within 1 week prior to start of treatment, and on Day 1 of every even numbered treatment cycle (2, 4, 6, etc ) and at the 
end of the study  
4 CT or MRI and biomarkers required at 8 week intervals after the start of treatment until the occurrence of progression of disease requiring discontinuation of further 
treatment  CT/MRI scans also to be obtained in any patient within 4 to 6 weeks to confirm complete / partial response assessments  Additional CT/MRI can be performed 
at the discretion of the physician to assess disease status as medically indicated   
 
 
 
5 Serum chemistries include glucose, creatinine, BUN, total bilirubin, AST, ALT, 
 alkaline phosphatase, serum albumin, total protein, Na, K, calcium, Cl, CO2, 
magnesium and phosphorus   More frequent laboratories required in event of ≥ Grade-3 toxicity  
6 Only IV or prescription anti-infectives or medications for GI toxicity will be recorded  
7 VS’s obtained prior to 1st infusion, every 15 min for the first hour, then every 30 min until completed, at completion, and then 30 min post-infusion  In absence of 
significant changes, may be reduced with subsequent doses to prior to infusion, at 30 min, and then at completion  
8 Ongoing AEs until resolved, new events attributed to test article; otherwise, deaths, hospitalizations, or events requiring IV or prescription anti-infectives or 
medications related to GI toxicity  
 
 
 
10 EKG required after completion of day 1 infusion of every even numbered treatment cycle (2, 4, 6, 8, etc ) and at the end of the study  
11 PE, Urinalysis, 
 & PT/PTT at baseline, at day 1 of every even numbered treatment cycle (2, 4, 6, 8, etc ) and at the end of the study   
 
 
12 
Patients who 
have biopsiable lesion and consented to biopsy will provide as many tumor metastasis biopsy samples as possible  
13 
 
 
 
NOTE: Unless otherwise specified, collection windows for study time points are nominally within ± 10% or according to institutional standard procedures. Planned 
deviations in treatment schedule are allowable up to 7 days due to holidays, vacation or personal reasons. 
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TABLE OF CONTENTS 
SYNOPSIS ...................................................................................................................................... 2 
LIST OF ABBREVIATIONS ....................................................................................................... 15 
1. 
INTRODUCTION ..................................................................................................... 16 
2. 
STUDY OBJECTIVES .............................................................................................. 20 
2.1. 
Primary Objective ...................................................................................................... 20 
2.2. 
Secondary Objectives ................................................................................................. 20 
3. 
STUDY DESIGN ....................................................................................................... 21 
4. 
PATIENT POPULATION ......................................................................................... 24 
4.1. 
Inclusion Criteria ........................................................................................................ 24 
4.2. 
Exclusion Criteria ...................................................................................................... 25 
4.3. 
Concomitant Medications and Procedures ................................................................. 26 
5. 
DOSE ESCALATION ............................................................................................... 28 
6. 
STUDY PROCEDURES ........................................................................................... 28 
6.1. 
Informed Consent ....................................................................................................... 28 
6.2. 
Patient Registration .................................................................................................... 28 
6.3. 
Pre-Study/Baseline Evaluations ................................................................................. 28 
6.4. 
3-Week Treatment Cycle Procedures......................................................................... 30 
6.5. 
Pharmacokinetic Evaluations ..................................................................................... 31 
6.6. 
Final Study Evaluation or Unscheduled/Early Termination Visit ............................. 32 
6.7. 
Long-Term Follow-Up ............................................................................................... 32 
6.8. 
Criteria for Removal from Protocol Treatment .......................................................... 33 
7. 
STUDY DRUG INFORMATION ............................................................................. 34 
7.1. 
Description of Study Drug ......................................................................................... 34 
7.2. 
Drug Accountability ................................................................................................... 34 
 
 
7.4. 
Study Drug Treatment ................................................................................................ 35 
7.4.1. 
Preventative Medications ........................................................................................... 35 
7.4.2. 
Vital Signs .................................................................................................................. 36 
7.4.3. 
Intravenous Administration ........................................................................................ 36 
7.4.4. 
Managing Infusional Toxicity .................................................................................... 36 
7.4.5. 
Dosing Schedule ........................................................................................................ 39 
7.4.6. 
Dose Reduction and Termination Guidelines ............................................................ 39 
7.4.7. 
Biopsy specimens ....................................................................................................... 40 
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8. 
STUDY EVALUATIONS ......................................................................................... 42 
9. 
ADVERSE EVENTS ................................................................................................. 43 
9.1. 
Serious Adverse Events ............................................................................................. 43 
9.2. 
Reporting AEs/SAEs.................................................................................................. 44 
9.3. 
Recording Information on AEs .................................................................................. 44 
9.4. 
Grading of AE Severity .............................................................................................. 45 
9.5. 
Pregnancy ................................................................................................................... 45 
9.6. 
Follow-up of Unresolved AEs ................................................................................... 45 
10. 
STATISTICAL CONSIDERATIONS ....................................................................... 46 
10.1. 
Overview and Study Design ...................................................................................... 46 
 
 
10.3. 
Safety Analysis .......................................................................................................... 46 
10.4. 
Efficacy Analysis ....................................................................................................... 47 
10.5. 
Other Evaluations ....................................................................................................... 47 
10.6. 
Interim Analysis ......................................................................................................... 48 
11. 
TREATMENT COMPLIANCE ................................................................................ 49 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................... 49 
13. 
DATA HANDLING AND RECORD KEEPING ..................................................... 50 
13.1. 
Case Report Forms ..................................................................................................... 50 
13.2. 
Record Retention ........................................................................................................ 50 
14. 
ADMINISTRATIVE REQUIREMENTS .................................................................. 51 
14.1. 
Good Clinical Practice ............................................................................................... 51 
14.2. 
Ethical Considerations ............................................................................................... 51 
14.3. 
Patient Information and Consent ................................................................................ 51 
14.4. 
Protocol Compliance .................................................................................................. 52 
14.5. 
Site Monitoring and On-Site Audits .......................................................................... 52 
14.6. 
Patient Data Protection ............................................................................................... 52 
14.7. 
Financial Disclosure ................................................................................................... 53 
14.8. 
Sponsor Discontinuation Criteria ............................................................................... 53 
15. 
DISSEMINATION AND PUBLICATION OF RESULTS....................................... 54 
16. 
REFERENCES ........................................................................................................... 55 
 
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LIST OF TABLES 
 
 
Table 2: 
Study Calendar ........................................................................................................... 11 
 
 
 
 
 
 
 
 
 
Table 7: 
Recommended Medications for Nausea, Vomiting and Diarrhea* ........................... 39 
Table 8: 
Reporting Requirements for Adverse Events ............................................................. 44 
Table 9: 
Grading of Adverse Event Severity ........................................................................... 45 
 
LIST OF APPENDICES 
Appendix 1. List of Standard Treatments for Each Cancer Type 
Appendix 2. Performance Status Evaluation  
Appendix 3. Procedure for Collection, Storage, and Shipment of Serum Samples  
Appendix 4. Response Evaluation Criteria in Solid Tumors (RECIST) 
Appendix 5. Procedure for Collection, Storage, and Shipment of Whole-Blood Sample                      
for UGT1A1 Genotyping 
Appendix 6. 
Tissue Sample Collection Instructions and Worksheet 
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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 
 
 
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 
CTCAE 
common terminology criteria for adverse events 
DLT 
dose limiting toxicity 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
HAHA 
human anti-human antibodies 
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 
IULN 
institutional upper limit of normal 
 
 
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 
PBS 
phosphate-buffered saline 
PK 
pharmacokinetics 
PR 
partial response 
RBC 
red blood cell 
SAE 
serious adverse event 
Trop-2 
Trophoblastic cell-surface antigen 
TTP 
time to progression 
WBC 
white blood cell 
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L 
INTRODUCTION 
January 23. 2020 
Over the past 60 years, antibodies have been investigated for their ability to shepherd toxic 
compounds, such as radioactivity, diugs, or toxins to tumors in an attempt to deliver these agents in a 
more selective manner for improved anti-tumor effects. While initially finding unconjugated 
antibodies to be largely ineffective, today there are several antibodies approved for clinical use in a 
variety of cancers, and there are many more under clinical evaluation. 0-6) Even though 
relatively few antibody conjugates have been approved for treating cancer, most antibodies are 
themselves incapable of eliciting sufficient responses to wanant their use as standalone agents. 
Instead, most unconjugated antibodies are combined with chemotherapeutic regimens in some way. 
Thus, it is not sm-prising that there has been a renewed interest in antibody-mug conjugates, 
paiiicularly with the recent success of the trastuzumab emtansine, an anti-HER2- maytansine 
conjugate, in HER2-positive breast cancer patients, even those who were refractory to 
unconjugated trastuzumab. a-9> 
Most of the antibody-di11g conjugates (ADC) being explored clinically today use dmgs that cannot 
be given alone because they ai-e too toxic (i.e., ultra-toxic). Conjugating these diugs, such as 
maytansine, calicheamicin, and am-istatin to antibodies detoxifies them, usually by altering their 
natural phaimacokinetic and biodistribution prope1iies. However, as the decision to remove 
Mylotai·g (gemtuzumab ozogamicin; anti-CD33-calicheamicin conjugate) from marketing suggests, 
the therapeutic window of these agents can be limited. oo, 11l For this reason, we have taken a 
closer look at the vai·ious chemotherapeutic agents that ah-eady have been tested clinically to 
dete1mine if any might be suitable for conjugation to antibodies. Since most chemotherapeutics 
require micromolai· concentrations for therapy, they ai·e not suitable for use as antibody conjugates. 
However, SN-38 is promising because it has activity in the low nanomolai· range, which is between 
the extreme of the ultratoxics that ai·e active in subnanomolar concentrations and most of the other 
commonly used chemotherapeutics. 
SN-38, a topoisomerase I inhibitor, is the active metabolite of the camptothecin CPT-11 (i1inotecan), 
which is approved as a single agent for colorectal cancer and included in treatment regimens such as 
FOLFIRI.<12-20> SN-38 is not water soluble, and therefore it was derivatized to a water-soluble fonn, 
irinotecan, but it must be enzymatically cleaved to the SN-38 fonn for it to have maximum potency. 
Unfortunately, at best, only 5% of irinotecan will be conve1ied to the active SN-38 fonn by 
esterase activity residing primarily in the liver, albeit there ai·e esterases in the tumor that can 
cleave irinotecan to SN-38.(21-24> Its catabolism in the liver results in its transport through the bile 
duct into the intestines, resulting in GI toxicity. 
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Immunomedics is currently pursuing several ADCs based on the SN-38 conjugation technology it 
developed.  In this protocol, a humanized anti-Trop-2 antibody (hRS7) is examined.  Trop-2 
(trophoblastic cell-surface antigen; also known as EGP-1, epithelial glycoprotein-1), 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(27), with much lower 
expression in normal tissues.(28)  Trop-2 has been implicated as an important antigen in oncogenesis, 
often being found in more aggressive tumors(29-39).  The murine RS7 antibody was initially identified 
as being specific for epithelial glycoprotein-1 (aka, Trop-2)(40, 41), being found in a number of 
different epithelial cancers and it was internalized(42-45), a highly desirable property for an antibody-
drug conjugate.  Indeed, as mentioned above, the initial studies with the SN-38 conjugates used an 
anti-CEACAM5 antibody that is not readily internalized, yet it was potent in vivo, leaving us to 
hypothesize that local release of the SN-38 from the antibody bound to the tumor provides an 
important mechanism for that conjugate’s activity.  However, the hRS7-SN-38 conjugate further 
benefits from the antibody’s ability to internalize.(46) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
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Since 8 of the 9 patients treated at 12 mg/kg required dose delays and reductions during the first 
cycle, that starting dose was considered to have exceeded the maximum acceptable dose for further 
consideration. In contrast, the initial dose level of 8 mg/kg appears acceptable with 3 additional 
patients (2 pancreatic, 1 gastric cancer). To establish a maximum acceptable dose level, a final 
intermediate dose level of 10 mg/kg was evaluated. 
Based upon these data from the Phase I portion of this study, starting doses of 8 or 10 mg/kg, 
administered on days 1 and 8 of a 21-day cycle were considered acceptable for further evaluation, 
and subsequently 10 mg/kg was selected for the ongoing Phase II portion of this study.  Severe (Grade 
3 or higher) toxicities have primarily included neutropenia, diarrhea and febrile neutropenia.  
Adverse events of all causalities (all grades and grade 3/4) are shown below. 
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Adverse events all grades and all causalities with incidence  5%. 
Adverse Event 
Preferred Term 
All Doses 
(N=203) 
8 mg/kg 
(N=82) 
10 mg/kg 
(N=109) 
12 mg/kg 
(N=9) 
18 mg/kg 
(N=3) 
Nausea 
36% 
52% 
22% 
56% 
100% 
Diarrhea 
35% 
48% 
19% 
67% 
67% 
Fatigue 
35% 
54% 
17% 
89% 
67% 
Neutropenia 
30% 
38% 
17% 
89% 
100% 
Alopecia 
29% 
41% 
18% 
44% 
33% 
Vomiting 
23% 
28% 
17% 
44% 
67% 
Anemia 
20% 
34% 
7% 
33% 
33% 
Abdominal pain 
17% 
18% 
13% 
33% 
67% 
Constipation 
16% 
27% 
9% 
22% 
0% 
Anorexia 
12% 
17% 
8% 
0% 
33% 
Hypokalemia 
10% 
13% 
6% 
33% 
33% 
Hypomagnesemia 
10% 
12% 
6% 
22% 
67% 
Edema peripheral 
10% 
16% 
4% 
22% 
33% 
Pyrexia 
9% 
15% 
4% 
22% 
0% 
Dizziness 
8% 
12% 
5% 
22% 
0% 
Dyspnea 
8% 
15% 
4% 
11% 
0% 
Headache 
7% 
13% 
4% 
0% 
0% 
Leukopenia 
7% 
11% 
4% 
22% 
0% 
 
Grade 3 and 4 adverse events all causalities  1%. 
Adverse Event 
Preferred Term 
All Doses 
(N=203) 
8 mg/kg 
(N=82) 
10 mg/kg 
(N=109) 
12 mg/kg 
(N=9) 
18 mg/kg 
(N=3) 
Neutropenia 
22% 
29% 
13% 
56% 
67% 
Febrile neutropenia 
4% 
2% 
5% 
11% 
0% 
Diarrhea 
3% 
4% 
4% 
22% 
0% 
Anemia 
2% 
10% 
2% 
22% 
0% 
Fatigue 
2% 
7% 
2% 
22% 
0% 
Abdominal pain 
2% 
2% 
1% 
0% 
67% 
Leukopenia 
2% 
5% 
3% 
0% 
0% 
Hypokalemia 
1% 
2% 
1% 
11% 
0% 
Hyponatremia 
1% 
4% 
1% 
0% 
0% 
Lymphopenia 
1% 
2% 
1% 
0% 
0% 
Nausea 
1% 
1% 
1% 
0% 
0% 
Urinary tract infection 
1% 
1% 
1% 
0% 
0% 
Vomiting 
1% 
1% 
1% 
0% 
0% 
In Phase I & Phase II, there was evidence of efficacy.  Partial responses have been observed 
currently in patients with triple-negative breast cancer, small-cell lung cancer, non-small- cell 
lung cancer, esophageal cancer, urinary bladder, and colorectal cancer.  Disease stabilization has 
been observed in many patients. 
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2. 
STUDY OBJECTIVES 
This is a first-in-man clinical study with the antibody-drug conjugate, IMMU-132, which uses the 
humanized antibody hRS7 to deliver the topoisomerase I inhibitor, SN-38, directly to Trop-2- 
expressing epithelial tumors. 
2.1. 
Primary Objective 
The primary objective in Phase I 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.  Dose escalation in Phase I (completed) was intended to determine a maximum 
acceptable dose and select cancer types for continued expanded study in Phase II.  Phase II 
continues enrollment with dose levels and cancers selected based upon Phase I results and 
preliminary efficacy results.  The primary objective in Phase II is the evaluation of the safety and 
efficacy of IMMU-132 administered in 3-week treatment cycles, at a dose selected in Phase I.  
2.2. 
Secondary Objectives 
 
In Phase I, the secondary objectives are to obtain initial data concerning pharmacokinetics, 
immunogenicity, and efficacy with this dosing regimen. In Phase II, secondary objectives also 
include pharmacokinetics and immunogenicity. 
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3. 
STUDY DESIGN 
This is a Phase I/II, open-label study of IMMU-132 in previously treated patients with the following 
metastatic epithelial cancers: 
 Gastric adenocarcinoma (GC) 
 Esophageal cancer (EC) 
 Hepatocellular carcinoma (HCC) 
 Non-small cell lung cancer (NSCLC) 
 Small-cell lung cancer (SCLC) 
 Epithelial ovarian cancer (EOC) 
 Cervical Cancer 
 Papillary thyroid cancer 
 Glioblastoma multiforme (GBM) 
 Endometrial Cancer 
 Triple-negative breast cancer (TNBC) 
 Non-triple-negative breast cancer (mBC) 
 Hormone-refractory prostate cancer (HRPC) 
 Head and neck cancers- squamous cell (SCCHN) 
 Renal cell carcinoma (clear cell) (RCC) 
 Urothelial cancers, including urinary bladder cancer. 
A table of approved or standard therapeutic regimens or regimens in documented clinical 
trials for each of these cancer types is included in Appendix 1. Patients who have not received 
all approved or standard treatments for their cancer must be informed that these alternatives to 
receiving IMMU-132 are available prior to consenting to participate in this trial. 
In Phase II, up to 150 patients (assessable) in in each of 5 cancer subtypes (TNBC, non-TNBC, NSCLC, 
SCLC, UC) and up to 56 patients (assessable) per other cancer types will be studied at the 10 mg/kg 
dose. 
Based upon the Phase I results, the 8 mg/kg and 10 mg/kg dose levels were selected for further 
evaluation in Phase II, and subsequently the 10 mg/kg dose was selected for the ongoing Phase II 
study. 
Baseline evaluations within 4 weeks of the scheduled start of treatment include patient history, 
physical examination with vital signs and performance evaluation, local histology review to confirm 
one of the epithelial cancers listed above, contrast-enhanced CT or MRI scans (chest, abdomen, 
pelvis with additional imaging of other involved areas), CBC (with differential and platelet count), 
routine serum chemistries, urinalysis, PT/PTT, EKG, and serum samples for human anti-human 
antibody (HAHA).  
 
 
 
 
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A single whole-blood sample (purple or pink-topped tube, 2 mL) will be collected from each 
registered patient prior to receiving IMMU-132 for determination of UGT1A1 or other UGT1 
genotype.  This sample will be shipped to Sponsor who will perform this assay.  The results are not 
used to establish eligibility but will be used for retrospective assessment of toxicity. 
All patients receive two doses of IMMU-132 administered in 3-week treatment cycles with weekly 
dosing in the first two weeks (days 1 and 8 of 21-day cycles) and no dosing the third week. In the 
ongoing Phase II portion of the study, all patients receive 10 mg/kg starting doses and the 
treatment cycles are to be continued in the absence of unacceptable toxicity or progression of disease 
requiring termination of further treatment.  The first determination of disease progression per 
RECIST1.1 does not require discontinuation of study treatment if there is still the potential for 
patient benefit in the opinion of the investigator, but treatment must be discontinued if subsequent 
imaging documents disease progression from that assessment. All patients are closely monitored 
over the course of their treatment, and NCI CTCAE v4.0 is used to grade all adverse events and to 
provide dose reduction, delay or cessation guidelines in the event of treatment-related toxicity. 
Based on irinotecan and animal testing, the major toxicity of IMMU-132 is expected to be 
gastrointestinal symptoms and hematologic suppression.  Growth factors and other supportive care 
are allowed when medically necessary any time during treatment with IMMU-132, but not 
prophylactically before start of treatment with the first IMMU-132 dose in cycle 1. 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
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Patients who exhibit an excessive cholinergic response to IMMU-132 treatment (e.g., abdominal 
cramping, diarrhea, salivation, etc.) can receive appropriate premedication (e.g., Atropine) for 
subsequent treatments. 
In Phase I, dose guidelines will be followed with a goal of being able to give the first cycle 
without requiring dose reduction, delay, or discontinuation or cytokine support at the time the second 
cycle is given. 
Study procedures during treatment include physical examination and vital signs, CBC (with 
differential and platelet count), routine serum chemistries, PT/PTT, serum samples for PK (to be 
collected in all patients in the ongoing Phase II study unless an exemption is approved by the 
Sponsor) and HAHA, concomitant medications and adverse events, and EKG. 
Starting with the initial dose of IMMU-132, CT (or MRI if needed) examinations are to be obtained 
at 8-week intervals until the occurrence of progression of disease requiring discontinuation of 
further treatment. For scans showing stable disease, but with substantial or rapid tumor shrinkage 
near threshold for a partial response, the 8-week interval for the next scan may be shortened at 
investigator discretion and if discussed with the medical monitor.  Confirmatory CT/MRI scans are 
to be obtained 4 to 6 weeks after an initial partial response and/or 4 to 6 weeks after an initial 
complete response. If a confirmatory scan is performed the subsequent scans will be scheduled 
every 8 weeks from the confirmatory scan. Tumor biomarkers are to be obtained at the time of 
radiologic evaluations. 
 
 
 
 
 
After discontinuing treatment, the patient will undergo an end-of-study evaluation, with additional 
follow-up only required until resolution or stabilization of any treatment-related toxicity.  Additional 
CT or MRI may be performed at the discretion of the physician to assess disease status as 
medically indicated. 
Long-term follow-up will continue in patients with stable disease or an objective response with 
evaluations performed every 3 months for up to 2 years or until progression of disease or initiation 
of other treatment.  All patients will be followed every month for survival, which may be by 
telephone, for no longer than 2 years from final study evaluation. 
Patients continuing to benefit from treatment at time of study closure may be eligible to enroll in a 
rollover study, so they may continue to receive treatment. 
 
(See study calendar for detailed schedule of study procedures) 
 
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4. 
PATIENT POPULATION 
The study population comprises previously treated adults with Stage IV (metastatic) epithelial 
cancers.  Eligible patients must satisfy the following entry criteria at time of study entry: 
4.1. 
Inclusion Criteria 
 Male or female patients, >18 years of age, able to understand and give written informed 
consent. 
 Histologically or cytologically confirmed epithelial cancer of one of the following 
types: 
 Gastric adenocarcinoma (GC) 
 Esophageal cancer (EC) 
 Hepatocellular carcinoma (HCC) 
 Non-small-cell lung cancer (NSCLC) 
 
 
 
 
 Small-cell lung cancer (SCLC) 
 Epithelial ovarian cancer (EOC) 
 Cervical Cancer 
 Endometrial Cancer 
 Triple-negative breast cancer 
 
 
 
 
 
 
 Non-triple-negative breast cancer 
 Papillary thyroid cancer (excludes follicular, medullary, Hurthle cell, and anaplastic 
thyroid cancer) 
 Glioblastoma multiforme (GBM)  
 Hormone-refractory prostate cancer (HRPC) 
 Head and neck cancers- squamous cell (SCCHN) 
 Renal cell cancer (clear cell) (RCC) 
 Urothelial cancer 
 
 
 
 
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January 23, 2020                         
 
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 Stage IV (metastatic) disease (except for patients with GBM). 
 Refractory to or relapsed after at least one prior standard therapeutic regimen. 
(Appendix 1 lists approved or standard chemotherapeutic agents for each cancer type. Patients who have 
not received all approved or standard treatments for their cancer must be informed that these alternatives 
to receiving IMMU-132 are available prior to consenting to participate in this trial.) 
 Adequate performance status (ECOG 0 or 1) (Appendix 2). 
 Expected survival > 6 months. 
 Measurable disease by CT or MRI. 
 At least 2 weeks beyond treatment (chemotherapy, investigational drugs including 
small molecular inhibitors, endocrine therapy, immunotherapy and/or radiation therapy) 
or major surgery and recovered from all acute toxicities to Grade 1 or less (except 
alopecia). 
 At least 2 weeks beyond high dose systemic corticosteroids (however, low dose 
corticosteroids < 20 mg prednisone or equivalent daily are permitted). 
 Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, 
ANC > 1,500 per mm3, platelets > 100,000 per mm3). 
 Adequate renal and hepatic function (creatinine ≤ 2.0 x IULN, bilirubin ≤ 1.5 IULN, 
AST and ALT ≤ 3.0 x IULN or 5 x IULN if know liver metastases). 
 Otherwise, all toxicity at study entry < Grade 1 by NCI CTCAE v4.0. 
4.2. 
Exclusion Criteria 
 Women who are pregnant or lactating. 
 Women of childbearing potential and fertile men unwilling to use effective contraception 
during study until conclusion of 12-week post-treatment evaluation period. 
 Patients with Gilbert’s disease. 
 Patients with brain metastases can be enrolled only if treated, non-progressive brain 
metastases and off high-dose steroids (>20 mg prednisone or equivalent) for at least 4 
weeks.   
 Presence of bulky disease (defined as any single mass >7 cm in its greatest dimension).  
Patients with a mass over 7 cm, but otherwise eligible, may be considered for enrollment 
after discussion and approval with the medical monitor. 
 Patients with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal 
obstruction. 
 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. 
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 Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive. 
 Known history of unstable angina, MI, or CHF present within 6 months or clinically 
significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti- 
arrhythmia therapy. 
 Known history of clinically significant active COPD, or other moderate-to-severe 
chronic respiratory illness present within 6 months. 
 Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation 
within 6 months of initiation of study treatment. 
 Infection requiring intravenous antibiotic use within 1 week. 
 Patients with a history of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI 
toxicity to prior irinotecan. 
 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. 
4.3. 
Concomitant Medications and Procedures 
 Patients enrolled in this trial will be refractory or relapsed after one or more chemotherapy 
regimens that may have included irinotecan. All of these treatments must be discontinued 
for a minimum of 2 weeks prior to starting IMMU-132, and these or other anti-cancer 
therapies (i.e., drugs, biologics, procedures) are not permitted during this study.  
However, palliative and/or supportive medications and procedures will be allowed at the 
investigator’s discretion. Patients who receive palliative and/or supportive medications 
and procedures should have a washout period of 1 week after the last IMMU-132 dose 
and 2 weeks prior to resuming the treatment with nextIMMU-132 dose, unless otherwise 
a different washout period is arranged by discussion with medical monitor. 
 Premedication with acetaminophen, steroids, and diphenhydramine or equivalents is not 
anticipated; however, it will be employed as clinically indicated to decrease infusion 
reactions.  Patients with a history of infusional reactions to other antibody therapies 
may be pre-medicated at the discretion of the treating physician. 
 Patients who exhibit an excessive cholinergic response to IMMU-132 treatment (e.g., 
abdominal cramping, diarrhea, salivation, etc.) can receive appropriate premedication (e.g. 
Atropine) for subsequent treatments. 
 Hematopoietic growth factors or blood transfusions are allowed at physician’s discretion, 
but not prophylactically before the first IMMU-132 dose in Cycle 1. 
 High dose systemic corticosteroids are not allowed within 2 weeks of study entry. 
 Low dose corticosteroids <20 mg prednisone or equivalent daily are permitted (topical 
steroids and corticosteroid inhalers are allowed). 
 Antiemetics, anti-diarrheal medications, cytokines or blood transfusions may be administered 
as clinically necessary. 
 Other supportive and palliative care is allowed as medically warranted. 
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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 SN38.  As such, all patients should be recommended to avoid the following while on study 
therapy: 
CYP 3A4 Inhibitors: 
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 
Troleandomyn 
Verapamil 
Voriconazole 
 
 
CYP 3A4 Inducers: 
Aminoglutethimide 
Bexarotene  
Bosentan 
Carbamazepine 
Efavirenz 
Fosphenytoin 
Griseofulvin 
Modafinil  
Nafcillin 
Nevirapine 
Oxcarbazepine  
Phenobarbital  
Phenytoin  
Primidone  
Rifabutin  
Rifampin  
Rifapentine 
St. John's wort 
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5. 
DOSE ESCALATION 
Dose escalation phase is now completed.  
6. 
STUDY PROCEDURES 
Blood samples obtained for HAHA and antibody / conjugate serum levels and UGT1A1 levels are 
to be shipped to the Sponsor 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. 
6.1. 
Informed Consent 
No study 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 for each of these cancer types is included in 
Appendix 1.  Patients who have not received all approved or standard treatment lines for their 
cancer must be informed that these 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 will be signed, dated, and witnessed, 
with a copy given to the subject. 
6.2. 
Patient Registration 
Since this Phase I /II trial is being performed at multiple institutions and in different cancers, 
investigators must contact the Clinical Project Manager (Sponsor) or designee in advance of 
consenting and start screening a patient to determine if or when a patient may be enrolled. This is 
particularly important because a number of clinical sites are enrolling patients and the Sponsor needs 
to plan enrollment in specific tumor types relative to product supply. 
Eligible patients will be enrolled in the study by calling the Clinical Project Manager or designee at 
Immunomedics at 
Monday through Friday, between 8:30 AM and 5:00 PM EST. The 
screening CRF pages are to be completed and faxed to Immunomedics at 
 or emailed 
to register the patient at least 48 hours prior to the expected treatment start date. 
6.3. 
Pre-Study/Baseline Evaluations 
Required within the 4 weeks prior to treatment: 
 
 Signed informed consent 
 
 
 
 Hepatitis B surface antigen test, hepatitis C antibody test 
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 Documented histology review to confirm epithelial cancer of one of the following types: 
 Gastric adenocarcinoma (GC)  
 Esophageal cancer (EC)  
 Hepatocellular carcinoma (HCC)  
 Non-small-cell lung cancer (NSCLC) 
 Small-cell lung cancer (SCLC) 
 Epithelial ovarian cancer (EOC) 
 Cervical Cancer 
 
Endometrial Cancer 
 Triple-negative breast cancer (TNBC)  
 Non-triple-negative breast cancer 
 Glioblastoma multiforme (GBM) 
 Papillary thyroid cancer 
 Hormone-refractory prostate cancer (HRPC) 
 Head and neck cancers - squamous cell (SCCHN) 
 Renal cell cancer (clear cell) (RCC) 
 Urothelial cancers. 
 Medical/surgical history review with treatment history to include treatment response and 
also time to progression for last therapy regimen 
 Concomitant medications review 
 Physical examination with vital signs 
 Standard 12-lead electrocardiogram (EKG) 
 CBC including platelet count, with WBC differential in absolute cell counts 
 Routine serum chemistries (i.e., glucose, creatinine, BUN, total bilirubin, AST, ALT, 
, alkaline phosphatase, serum albumin, total protein, Na, K, calcium, Cl, CO2, 
magnesium and phosphorus) 
 Serum sample for HAHA (frozen, to be shipped to Sponsor for analysis) 
 Urinalysis 
 PT/PTT 
 CT or MRI with contrast (chest, abdomen, pelvis, other regions of known/suspected 
involvement)* 
 
 
 
 
 
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 A single whole-blood sample (purple or pink-topped tube, 2 mL) to be collected from 
each registered patient prior to receiving IMMU-132 for determination of UGT1A1 
genotype. 
* MRI abdomen and pelvis with contrast may be done in situations where a CT with contrast 
is equivocal or contraindicated.  A non-contrast chest CT should be done for patients 
requiring an MRI of the abdomen and pelvis. 
6.4. 
3-Week Treatment Cycle Procedures 
Treatment Days [Days 1 & 8 (+/- 1 day) of each cycle] 
 IMMU-132 dose preparation and administration 
 Vital signs (Prior to first infusion and every 15 minutes for the first hour then every 30 
minutes until completing IV administration, 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.)  
  Blood samples prior to infusion: 
 CBC (with differential and platelet count) 
 Serum chemistry panel (glucose, creatinine, BUN, total bilirubin, AST, ALT, 
, alkaline phosphatase, serum albumin, total protein, Na, K, calcium, Cl, 
CO2, magnesium and phosphorus) 
 PT/PTT [required only on Day 1 of all even numbered cycles (cycle 2, 4, 6, 8, 
etc.)] 
 Urinalysis (required only on Day 1 of all even numbered cycles starting with cycle 2) 
 Physical examination (required only on Day 1 of all even numbered cycles starting with 
cycle 2) 
 12-lead EKG done [required after completing infusion on Day 1 of all even numbered 
cycles (cycle 2, 4, 6, 8, etc.)] 
 Concomitant medications (continued, changed) 
 Adverse event reporting 
 Serum samples for PK analysis: (frozen, to be shipped to Sponsor for analysis). 
 
 
 
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If samples are not collected with the first dose, then all samples should be obtained with 
the first dose of a subsequent cycle as advised by the Sponsor. 
 HAHA sample (frozen, to be shipped to Sponsor for analysis) 
 
 
 Pregnancy test, if applicable [required only on Day 1 of all even numbered cycles (cycle 
2, 4, 6, 8, etc.)] 
CT or MRI examinations 
  Starting with the initial dose of IMMU-132, 
CT or MRI scans 
 and are to be obtained at 8 week intervals 
after the first treatment dose until the occurrence of progression of disease requiring discontinuation 
of further treatment. For scans showing stable disease, but with substantial or rapid tumor shrinkage 
near threshold for a partial response, the 8-week interval for the next scan may be shortened at 
investigator discretion and if discussed with the medical monitor. Confirmatory CT/MRI scans are to 
be obtained in any patient within 4 to 6 weeks of an initial partial response and/or complete 
response. If a confirmatory scan is performed, then subsequent scans will be scheduled every 8 
weeks from the date of confirmatory scan. 
Note: MRI abdomen and pelvis with contrast may be done in situations where a CT with contrast is 
equivocal or contraindicated.  A non-contrast chest CT should be done for patients requiring an 
MRI of the abdomen and pelvis. 
Additional CT or MRI studies may be performed at the discretion of the physician to assess disease 
status as medically indicated. 
If patient does not experience unacceptable toxicity or progression of disease requiring 
discontinuation of treatment, treatment cycles may be continued. Patients, who have progression of 
disease assessed for the first time during the study but derive continued clinical benefit from IMMU-
132 treatment, may continue to be treated based on physician discretion and approved by Sponsor. 
6.5. 
Pharmacokinetic Evaluations 
Serum for PK analysis in the ongoing Phase II study will be obtained in all patients (unless 
exempted by the Sponsor) with the first dose of cycle 1 (i.e., Cycle 1, Day 1).  
 
 
 
 
 
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6.6. 
Final Study Evaluation or Unscheduled/Early Termination Visit 
To be conducted 14 days after the last dose of study drug or in the event of premature study 
termination 
 12-lead electrocardiogram (EKG) 
 Physical examination (complete) 
 Pregnancy test, if applicable 
 Vital signs 
 Blood samples 
 CBC (with differential and platelet count) 
 Serum chemistry panel 
 PT/PTT 
 
 
 Serum sample for HAHA (frozen, to be shipped to Sponsor for analysis) 
 
 
 Urinalysis 
 Concomitant medications (continued, changed) 
 Adverse event reporting 
6.7. 
Long-Term Follow-Up 
After completing the final study evaluation, follow-up continues for patients who have not 
progressed with assessments including CT or MRI studies performed every 3 months for up to 2 
years or until progression of disease or initiation of other treatment. Follow-up will also include 
physical exam, CBC, chemistries, 
 
(Note: MRI abdomen and pelvis with contrast may be done in situations where a CT with contrast 
is equivocal or contraindicated.  A non-contrast chest CT should be done for patients requiring an 
MRI of the abdomen and pelvis). 
Follow-up is also required at least every 3 months until resolution or stabilization for any treatment-
related abnormalities that warrant continued monitoring in patients who progressed and otherwise 
would have completed the study. 
Adverse events and concomitant medications reported at any follow-up visits will include outcome 
of any ongoing unresolved events, new events attributed to the study treatment, deaths, 
hospitalizations, and infectious episodes requiring prescription or IV anti-infectives or GI toxicity. 
All patients will be followed every month for survival, which may be by telephone.  Patients will not 
be followed beyond 2 years from final study evaluation. 
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6.8. 
Criteria for Removal from Protocol Treatment 
Patients may be removed from protocol treatment under the following conditions: 
 First documentation of progressive disease (Physician discretion and Sponsor 
approval to continue) or symptomatic deterioration indicating treatment failure. 
 Patients who want to continue treatment after radiological documentation of progressive 
disease should notify the physician who will obtain Sponsor approval before treatment 
continuation. 
 Unacceptable toxicity. 
 Treatment delay for any reason > 3 weeks (Treatment delays of up to 3 weeks will be 
allowed at the investigator’s discretion). 
 The patient may withdraw from the study at any time for any reason. 
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7. 
STUDY DRUG INFORMATION 
7.1. 
Description of Study Drug 
hRS7 is a CDR-grafted, humanized monoclonal IgG1 anti-Trop-2 antibody.  The antibody is 
prepared using cell culture methods by Immunomedics, Inc. (Morris Plains, NJ) 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)  
  
 
 
 
 
  
 
 
 
Complete and detailed drug preparation and storage instructions in addition to the management of 
drug accountability are provided in the Pharmacy Manual, which should be used as the primary 
reference for these activities. 
7.2. 
Drug Accountability 
All vials of study drug must be stored under refrigeration (monitored at 2-8oC) and protected from 
light in a locked room that can be accessed only by the pharmacist, the study Investigator, or another 
duly designated person.  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 directed by this 
protocol without prior 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.  Alternatively, after notification, all unused products 
will be collected by the Study Monitor and returned to Immunomedics. 
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7.4. 
Study Drug Treatment 
7.4.1. 
Preventative Medications 
Pre-medication with acetaminophen, diphenhydramine, corticosteroids, Histamine H2 antagonists 
(i.e., Pepcid or equivalent) or other drugs is not anticipated; however, it will be employed as 
clinically indicated to decrease infusion reactions.  Patients with a history of infusional reactions to 
other antibody therapies or who develop reactions to this study agent may be pre-medicated at the 
discretion of the treating physician. 
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7.4.2. 
Vital Signs 
Vital signs will be assessed prior to first infusion every 15 ± 5 minutes for the first hour and then 
every 30 minutes until completing IV administration, 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. 
7.4.3. 
Intravenous Administration 
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.  
 
 
 
 
 
 
 
 
 
 
 
7.4.4. 
Managing Infusional Toxicity 
Immunomedics, Inc., should be notified within 24 hours in the event of any serious infusion 
reaction. 
NCI CTCAE  version  4.0  is  used  to  grade  all  adverse  events  and  to  provide  management 
guidelines for infusional toxicity. 
For a serious infusion reaction considered severe or life threatening (NCI toxicity Grade 3 or 
higher) an 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. 
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Recommended actions for mild toxicity (Grade 1 events) include slowing the remaining infusion 
rate. 
Any infusional toxicity must have resolved to ≤ Grade 1 prior to a patient receiving the next 
scheduled infusion. 
 
 
 
 
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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 i.v. 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 this study agent.  Hospital or institutional 
guidelines may exist and should be consulted for recommended treatment of these conditions in 
patients received cancer therapy. Several major oncology organizations have also provided 
comprehensive guidelines for optimal medical management of nausea, vomiting and diarrhea 
with cancer treatment. As of this writing, guidelines from these organizations are not stratified by 
toxicity Grade. A partial list of the major medications is provided below, but the hospital/institution 
guidelines or the references below should be consulted for more detailed information as to 
management of these conditions. 
Patients who exhibit an excessive cholinergic response to IMMU-132 treatment (e.g., abdominal 
cramping, diarrhea, salivation, etc.) can receive appropriate premedication (e.g. Atropine) for 
subsequent treatments. 
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Table 7: 
Recommended Medications for Nausea, Vomiting and Diarrhea* 
Agent 
Dose/Frequency 
For Prevention of Acute Emesis: 
Palonosetron 
0.075mg 
Decadron 
10-20 mg 
10 mg every 12 hours 
Granisetron 
1 mg or 0.01 mg/kg 
1-2 mg daily 
Ondansetron 
8 mg or 0.15 mg/kg 
16-24 mg daily 
Lorazepam 
0.5-2 mg every 4-6 hours 
Alprazolam 
0.5-2 mg every 4-6 hours 
For Delaved Emesis: 
Aprepitant 
125 mg on Day 1 followed by 80 mg on Days 2 & 3 
Fosaprepitant 
115 mg day 1 only 
For Diarrhea: 
4 mg initially followed by 2 mg with eve1y episode 
Loperamide 
for a maximum of 16 mg daily. Discontinue 12 hours after 
diaIThea resolves and nonnal diet is resumed. 
Octreotide 
100-150 mcg three times daily 
Fluoroquinolones (for diaiThea 
(e.g., ciprofloxacin 250-750 mg eve1y 12 hours for 7 
persisting > 24 hrs., ANC <500 or 
days) 
fever with diaIThea) 
January 23. 2020 
Route of 
administration 
PO or IV 
PO or IV 
IV 
PO 
IV 
PO 
PO or sublingual 
PO or sublingual 
PO 
IV 
PO 
Subcutaneously 
PO 
* Based on NCCN Antiemes1s Gmdehnes vl.2011; Benson et al (2004) Recommended gmdehnes for the treatment of 
cancer treatment-induced diaIThea. J Clin Oncol 22:2918-26; Kris et al (2006) American Society of Clinical 
Oncology guidelines for antiemetics in oncology: Update 2006. J Clin Oncol 24:2932-47. 
7.4.5. 
Dosing Schedule 
All patients receive IMMU-132 to be administered in the ongoing Phase II study at 10 mg/kg 
weekly for 2 consecutive weeks (2 weekly doses plus 1 week without treatment represents a 
single 3 week cycle). Treatment can be continued without a rest period in the absence of progression 
of disease or unacceptable toxicity. Planned deviations in treatment schedule are allowable up to 7 
days due to holidays, vacations or personal reasons. 
7.4.6. 
Dose Reduction and Termination Guidelines 
The major toxicities of IMMU-132 are expected to be gastrnintestinal symptoms and 
hematologic suppression. All patients are closely monitored over the course of their ti·eatment. 
NCI CTCAE v4.0 is used to grade all adverse events and to provide the following dose 
reduction, delay or cessation guidelines in the event of treatment-related toxicity. 
In the ongoing Phase II study, patients will receive 10 mg/kg IMMU-132 once weekly for 2 
consecutive weeks followed by 1 week rest in cycles of 21 days, with ti·eatment continued in the 
absence of progression or unacceptable toxicity. Neutropenia, GI toxicity, and alopecia were the 
most common toxicities in Phase I testing. All patients will be closely monitored over the course 
of their ti·eatment, with NCI CTCAE v4.0 used to grade all adverse events and to provide dose 
reduction, delay or cessation guidelines in the event of toxicity. 
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7.4.7. 
Biopsy specimens 
At the discretion of treating physician, patients who have biopsiable lesion(s) and consented to 
biopsy(ies) will provide before and during the study as many tumor metastasis core biopsy samples 
(~0.2 to 0.5 cm3) as possible.  
Procedure for Handling Core Biopsies 
Samples should be shipped to Immunomedics to perform research assays intended to detect a variety 
of biomarkers, 
.  The 
purpose of this testing is to develop a database that will be used to assess biomarker status versus 
anti-tumor  response to IMMU-132.  Immunomedics recommends investigators participating in the 
collection of core biopsy samples consult with their institutional Pathology Department for the 
processing and handling of specimens.  While some of the testing can be performed on 
conventionally preserved specimens (i.e., fixed in 10% buffered formalin), other assays require fresh 
tissue that should be snap frozen in liquid nitrogen or another suitable method typically used by 
Pathology Departments to prepare frozen tissues for RNA, protein, and microscopic examination.  
Thus, Immunomedics is requesting both formalin-fixed and fresh/frozen tissues according to the 
procedure described below: 
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If possible, obtain 4-6 core biopsy samples from sites of confirmed cancer.  If 4 cores are obtained, 2 
should be placed in 10% buffered formalin, the other 2 should be flash frozen (6 cores, split 3+3; 2 
cores, split 1+1; odd number cores, process more by flash freezing). 
a. 10% buffered formalin:  Place specimens in suitable leak-free container.  Add enough 
formalin to cover completely.  Ensure specimen is completely immersed.  Sample can be 
stored at room temperature or in refrigerator prior to shipping.  Sample should remain in 
the fixative at least overnight before shipping.  When shipping, the vessel containing the 
tissue should be filled with formalin as much as possible so that tissue will remain in 
contact with the formalin. 
b. Flash-frozen:  Tissues processed in this manner are best handled by the 
Pathology/Histology department.  The core biopsies should be placed in a small amount 
of saline to transport.  The tissue is then gently blotted dry, placed in a cassette containing 
a small amount of a cryoprotective embedding media (e.g., OCT compound).  The 
cassette is then partially filled with this compound to cover tissue and then snap-frozen 
using a freezing spray or liquid nitrogen.  Ship to Immunomedics frozen on dry ice. 
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8. 
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, vital 
signs, and EKG.  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 v4.0 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 4 to classify tumor response, time to onset of objective response, duration of objective 
response, and time to progression.  Overall survival will be determined. 
Pharmacokinetics (PK) will be evaluated from serum samples using an ELISA assay performed by 
the Sponsor.  The results will be characterized by standard PK parameters including peak and trough 
values, area-under-the-curve (AUC), maximum concentration (Cmax), and half-life (T1/2), if feasible, 
and summarized using descriptive statistics. 
Immunogenicity will be determined from serum samples using an ELISA assay performed by the 
Sponsor for the occurrence of HAHA, that is, the presence of any human antibodies against IMMU-
132.  The occurrences of any positive HAHA results will be characterized by descriptive statistics. 
The UGT1A1 genotype (or another UGT1 genotype) will be determined at baseline and compared 
to hematological toxicity (see Appendix 5 for procedure for whole blood sample collection and 
shipping). 
 
 
 
 
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9. 
ADVERSE EVENTS 
All patients must be carefully monitored for 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 CTCAE version 4.0. 
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: 
1. 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. 
2. Significant or unexpected worsening or exacerbation of the condition/indication under 
investigation. 
3. A suspected drug interaction. 
4. An intercurrent illness. 
5. 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. 
9.1. 
Serious Adverse Events 
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 
6. Other important medical events may also be considered SAEs if they may 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 inpatient hospitalization, development of drug 
dependency or drug abuse). 
An SAE does not include: 
1. Progression of the underlying 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. 
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9_2_ 
Reporting AEs/SAEs 
January 23. 2020 
The fuvestigator is to report all AEs directly observed or spontaneously repoited by patients 
using concise medical tenninology on the appropriate CRF. 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?" 
The AE repo1iing period begins with the first dose of study diug and ends with the last scheduled 
study evaluation or until all diug related toxicities and ongoing AEs have resolved, whichever is 
later. 
All AEs/SAEs or exposure during pregnancy must be reported to hnmunomedics or its designee, 
whether or not considered related to study medication using the appropriate fo1ms/procedure. For 
SAEs, the Sponsor designated contact is to be notified by the fuvestigator, using the designated 
f01m, within 24 hours of awareness of the event. The initial repo1i is to be followed by 
submission of more detailed SAE infonnation within 5 calendar days of the event. 
Clinical Research Depaiiment 
hnmunomedics, fuc. 
300 The American Road 
Monis Plains, NJ 07950 
PPD 
Repo1iing requirements for AEs are summai·ized in the following table: 
Table 8: 
Reporting Requirements for Adverse Events 
Reporting Time 
Type of Report 
Within 24 hours 
Initial repo1t on designated SAE form 
SERIOUS 
Within 5 calendar days 
Follow-up/Final report on designated form 
NON-SERIOUS 
Per CRF submission procedure 
Appropriate CRF pages 
9.3. 
Recording Information on AEs 
All AEs, whether observed by the fuvestigator, elicited from, or volunteered by the patient, will be 
recorded including: duration, severity, relationship to the study medication, treatment, action taken 
with respect to the study medication and outcome. When possible, all events should be reported 
in diagnostic te1ms or the most acceptable medical te1ms in order to inte1pret safety inf 01m ation 
accurately. 
The investigator must review all laboratory and test data and record any adverse events. The 
same fo1mat will be used as for other adverse events, regai·dless whether related to study therapy or 
not, including event severity grading, attribution, and resolution. A summary listing of all adverse 
events occmTing during the past yeai· on this study will be provided in progress repo1is reported to 
regulatory authorities. 
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The investigator will notify Immunomedics or its designee if he/she becomes aware at any time, 
during or following the study, of the occurrence of death or new malignancy involving the 
paiiicipant of a clinical trial, even though the event may not appeai· to be dmg related. 
9 .4. 
Grading of AE Severity 
The severity of AEs will be graded using the CTCAE Version 4.0. For each event, the highest 
severity grade should be reported. If a CTCAE criterion does not exists, the Investigator should use 
the grade or adjectives as described in Table 9. 
Table 9: 
Grading of Adverse Event Severity 
Grade 
Adjective 
Desc1iption 
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 
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. 
9 .5. 
Pregnancy 
The Sponsor must be notified of any patient or partner of a male patient becoming pregnant during 
the study, and any pregnancy must be followed until completion or te1mination of pregnancy. In the 
case of a live biith, the "no1mality" of the newborn can be assessed at the time of bnih. The 
"no1mality'' of an abo1ied fetus can be assessed by gross visual inspection unless pre-abortion 
laboratory findings ai·e suggestive of a congenital anomaly. 
9.6. 
Follow-up of Unresolved AEs 
All AEs should be followed until they are resolved, or the Investigator assesses them as chronic or 
stable or the patient's paiticipation in the trial ends (i.e., until a final repo1i is completed for that 
patient). Instmctions for repo1i ing changes in an ongoing AE during a patient's paiticipation in the 
trial ai·e provided in the instructions that accompany the AE CRFs. 
In addition, all AEs and SAEs assessed by the Investigator as possibly related to the investigational 
medication/product should continue to be followed even after the patient's paiiicipation in the ti·ial 
is over. Such events should be followed until they resolve or until the Investigator assesses them 
as "chronic" or "stable." Resolution of such events is to be documented on the appropriate CRF. 
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10. 
STATISTICAL CONSIDERATIONS 
10.1. 
Overview and Study Design 
This is an open label, non-randomized Phase I/II study in patients with a variety of 
refractory/relapsed metastatic epithelial cancers.  Prior use of irinotecan or other camptothecin-
derived agents (e.g., topotecan) is allowed except when there is a known history of anaphylactic 
reaction or ≥ Grade 3 GI toxicity to prior irinotecan.  The primary objectives of Phase I are to 
evaluate the safety and tolerability of several dose levels of the antibody-drug conjugate IMMU-132 
(hRS7-SN-38).  The secondary objectives are to obtain preliminary information on efficacy, 
pharmacokinetics, and immunogenicity. The primary objective in Phase II is the evaluation of the 
safety and efficacy of IMMU-132 administered in 3-week treatment cycles, at a dose selected in 
Phase I; secondary objectives also include pharmacokinetics and immunogenicity. 
The dose escalating phase has been completed and 12 mg/kg (on Days 1 and 8 of a 21-day cycle 
identified as the MTD. The Phase II expansion is ongoing at 10 mg/kg dose level, including 
enrollment currently focusing on 5 expansion cohorts (TNBC, non-TNBC, NSCLC, SCLC, UC).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
10.3. 
Safety Analysis 
In general, all patients administered any dose of study drug will be included in the evaluation of 
safety. 
Dose escalation continued for determination of the MTD, but for the Phase II portion of the protocol, 
the Sponsor will select 2 dose levels; one where at least 2 of 6 patients can complete the first 
cycle without ≥ Grade 3 toxicity and the other a lower dose level. 
 
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The frequency and severity of adverse events (AEs) will be tabulated by MedDRA Preferred Term 
and System Organ Class (SOC) for each dose group.  AEs will be classified using the MedDRA 
version 10 with severity assessed by NCI CTCAE v4 toxicity grades.  The frequency of AEs will 
be tabulated by MedDRA System Organ Class (SOC) and Preferred Term for each dose group.  For 
this purpose, an AE that occurs more than once within each patient will be counted only once (at the 
worst CTCAE grade and relationship category).  In the same fashion, similar AEs will be 
consolidated using the worst CTCAE grade and relationship category observed prior to classification 
into each MedDRA SOC. 
AEs  leading  to  death  or  to  discontinuation  from  treatment,  as  well  as  all  SAEs  will  be 
summarized separately, if appropriate.  The reasons for discontinuation will also be summarized for 
each dose group using frequency distributions. 
Both actual and change-from-baseline data on vital signs will be summarized using descriptive 
statistics by dose 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 dose 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 in a shift table for each parameter 
by dose group.   
Similarly, data on human anti-hRS7 antibody responses (HAHA) will be listed and summarized by 
descriptive statistics, if appropriate.  In addition, PK data documenting the clearance of SN-38 in a 
select number of patients will be used to gain preliminary information on the conjugate’s 
clearance properties, focusing on the area under the curve for total SN-38 (IgG-bound and free) and 
free SN-38.  This value potentially could helpful for assessing toxicity. 
Furthermore, the UGT1A1 genotype will be determined at baseline and compared to hematological 
toxicity. 
10.4. 
Efficacy Analysis 
In general, all patients who were treated with at least one complete cycle of study drug and have 
available response assessment data will constitute the efficacy population and be included in the 
analysis of efficacy. 
The objective response rate (ORR) and duration of response, will be tabulated and summarized by 
descriptive statistics for patients in each indication.  Progression-free survival (PFS) and overall 
survival (OS) will be summarized, either by tabulation, or, if feasible, by Kaplan-Meier 
methodology. Other efficacy analysis may be performed as appropriate.  
10.5. 
Other Evaluations 
Because of the escalation design, the dose levels and the number of patients entered on each dose 
level in this study cannot be determined in advance. Pre - and post-dose serum samples for peak and 
trough drug concentrations will be collected in all patients.  Once the MTD level is known, 
additional patients accrued to that level will have additional serum taken to better define the rate of 
clearance after each injection.  This will provide adequate data to allow for the determination of 
potential drug accumulation with repeated dosing. Antibody pharmacokinetics will be evaluated in a 
separate report based on blood levels of IMMU-132 from a subgroup of patients as measured by the 
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Sponsor in order to characterize concentration levels during treatment (See Study Calendar for 
time points). 
Descriptive statistics will be used to summarize both peak and trough values at each infusion as well 
as values measured at other time-points.  Formal pharmacokinetic analysis based on a non-
compartmental model will be performed on patients with adequate serum concentration data, if 
feasible.  Additional analyses may also be performed to evaluate serum levels of SN-38, if feasible, 
and to study the correlations between IMMU-132 concentrations and various treatment outcomes. 
10.6. 
Interim Analysis 
No formal interim analysis is planned during the course of this study. 
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11. 
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. 
12. 
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 
Immunomedics, 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 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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13. 
DATA HANDLING AND RECORD KEEPING 
13.1. 
Case Report Forms 
A CRF is required and must be completed for each enrolled patient.  The completed original 
CRFs 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 CRFs. 
CRFs 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 CRFs.   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 CRFs must match those charts.  In some cases, a 
portion of the source documents for a given study site may be the CRFs.  The Investigator must 
agree which items will be recorded in the source documents and for which items the CRF will stand 
as the source document. 
All entries in the CRF should be made legibly with black ballpoint pen.  Corrections to the CRF 
must be made by striking through the incorrect entry with a single line and entering the correct 
information adjacent to the incorrect data.  The correction must be initialed and dated by the 
person making the correction (ICH E6 4.9.3). 
13.2. 
Record Retention 
To enable evaluations and/or audits from regulatory authorities or Immunomedics, the Investigator 
agrees to keep records, including the identity of all participating patients (sufficient information to 
link records, CRFs and hospital records), all original signed informed consent forms, copies of all 
CRFs, source documents, and detailed records of treatment disposition.  The records must be 
retained by the Investigator until 2 years after the last approval of a marketing application in an ICH 
region and until there are no pending or contemplated marketing applications in an ICH region, or 
until at least 2 years have elapsed since the formal discontinuation of clinical development of the 
investigational product. However, study records may be retained for a longer period if required by 
local regulations. The Sponsor is responsible for informing the Investigators when these documents 
need no longer be retained. 
If the Investigator relocates, retires, or for any reason withdraws from the study, Immunomedics 
should be prospectively notified.  The study records must be transferred to an acceptable designee, 
such as another Investigator, another institution, or to Immunomedics. The Investigator must obtain 
Immunomedics written permission before disposing of any records. 
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14. 
ADMINISTRATIVE REQUIREMENTS 
14.1. 
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. 
14.2. 
Ethical Considerations 
This study is planned to be conducted both in the North America and in Europe, and 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. 
14.3. 
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 
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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 and 
the IRB/IEC. 
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. 
14.4. 
Protocol Compliance 
The Investigator will conduct the study in compliance with the protocol provided by Immunomedics, 
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 the 
Immunomedics.  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 
patients.  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.  
Immunomedics 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 Immunomedics, 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. 
14.5. 
Site Monitoring and On-Site Audits 
Monitoring and auditing procedures developed by Immunomedics or its designee will be followed, in 
order to comply with GCP guidelines.  On-site review of patient’s CRFs for completeness and 
clarity, cross-checking with source documents, and review of regulatory documents will be 
performed.  All available source documents should be obtained by the Investigator and provided to 
the Sponsor or 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, patients’ CRFs, and other study documentation 
for on-site audit or inspection. Direct access to these documents must be guaranteed by the 
Investigator, who must provide support at all times for these activities. 
14.6. 
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 
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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 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. 
14.7. 
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 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. 
14.8. 
Sponsor Discontinuation Criteria 
Immunomedics reserves the right to discontinue the trial at any time 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.  As directed by the 
Sponsor, all study materials will be collected and all CRFs completed to the greatest extent possible. 
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15. 
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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(CPT-11) metabolism and disposition in cancer patients. Clin Cancer Res. 1998;4:2747-54. 
25. 
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. 
26. 
Moon SJ, Tat F, Sheerin A, Zalath M, Arrojo R, Cardillo TM, et al. Cross-linker evaluation 
in the design of antibody-SN-38 conjugates for cancer therapy. Proc Amer Assoc Cancer Res. 
2010;51:591 (abst 2439). 
27. 
Alberti S, Trerotola M, Vacca G, Zappacosta R, Rossi C, Guerra E, et al. TROP2 is a major 
determinant  of  growth  and  metastatic  spreading  of  human  cancer.  J  Clin  Oncol. 
2007;25:Abst 10510. 
28. 
Trerotola M, Rathore S, Goel HL, Li J, Alberti S, Piantelli M, 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. 
29. 
Cubas R, Li M, Chen C, Yao Q. Trop2: a possible therapeutic target for late stage epithelial 
carcinomas. Biochim Biophys Acta. 2009;1796:309-14. 
30. 
Cubas  R,  Zhang  S,  Li  M,  Chen  C,  Yao  Q.  Trop2  expression  contributes  to  tumor 
pathogenesis by activating the ERK MAPK pathway. Mol Cancer. 2010;9:253. 
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Protocol: IMMU-132-01 
 
 
                             
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CONFIDENTIAL 
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31. 
Fang YJ, Lu ZH, Wang GQ, Pan ZZ, Zhou ZW, Yun JP, et al. Elevated expressions of 
MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver 
metastasis of colon cancer. Int J Colorectal Dis. 2009;24:875-84. 
32. 
Fong  D,  Moser  P,  Krammel  C,  Gostner  JM,  Margreiter  R,  Mitterer  M,  et  al.  High 
expression of TROP2 correlates with poor prognosis in pancreatic cancer. Br J Cancer. 
2008;99:1290-5. 
33. 
Fong D, Spizzo G, Gostner JM, Gastl G, Moser P, Krammel C, et al. TROP2: a novel 
prognostic   marker   in   squamous   cell   carcinoma   of   the   oral   cavity.   Mod   Pathol. 
2008;21:186-91. 
34. 
Guerra E, Trerotola M, Dell' Arciprete R, Bonasera V, Palombo B, El-Sewedy T, et al. A 
bicistronic CYCLIN D1-TROP2 mRNA chimera demonstrates a novel oncogenic mechanism 
in human cancer. Cancer Res. 2008;68:8113-21. 
35. 
Kobayashi H, Minami Y, Anami Y, Kondou Y, Iijima T, Kano J, et al. Expression of the 
GA733 gene family and its relationship to prognosis in pulmonary adenocarcinoma. 
Virchows Arch. 2010;457:69-76. 
36. 
Kobel M, Kalloger SE, Boyd N, McKinney S, Mehl E, Palmer C, et al. Ovarian carcinoma 
subtypes   are   different   diseases:   implications   for   biomarker   studies.   PLoS   Med. 
2008;5:e232. 
37. 
Ohmachi T, Tanaka F, Mimori K, Inoue H, Yanaga K, Mori M. Clinical significance of 
TROP2 expression in colorectal cancer. Clin Cancer Res. 2006;12:3057-63. 
38. 
Stepan LP, Trueblood ES, Hale K, Babcook J, Borges L, Sutherland CL. Expression of 
trop2 cell surface glycoprotein in normal and tumor tissues: potential implications as a cancer 
therapeutic target. J Histochem Cytochem. 2011;59:701-10. 
39. 
Wu H, Xu H, Zhang S, Wang X, Zhu H, Zhang H, et al. Potential therapeutic target and 
independent prognostic marker of TROP2 in laryngeal squamous cell carcinoma. Head Neck. 
2012. 
40. 
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. 
41. 
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. 
42. 
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. 
43. 
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. 
44. 
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. 
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Protocol: IMMU-132-01 
 
 
                             
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CONFIDENTIAL 
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45. 
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. 
46. 
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. 
47. 
Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Arrojo R, Liu D, Rossi EA, Chang CH, 
Goldenberg DM. Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-
Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. 
Bioconjug Chem. 2015;26(5):919-31 
48. 
Sharkey RM, McBride WJ, Cardillo TM, Govindan SV, Wang Y, Rossi EA, Chang CH, 
Goldenberg DM. Enhanced Delivery of SN-38 to Human Tumor Xenografts with an Anti-
Trop-2-SN-38 Antibody Conjugate (Sacituzumab Govitecan). Clin Cancer Res. 2015 Jun 23. 
[Epub ahead of print]. 
49. 
Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM. Trop-2 is a novel 
target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug 
conjugate (ADC).  Oncotarget.  2015 Jun 18. [Epub ahead of print]. 
50. 
Starodub AN, Ocean A, Shah MA, Guarino MJ, Picozzi VJ Jr, Vahdat LT, Thomas SS, 
Govindan SV, Maliakal PP, Wegener WA, Hamburger SA, Sharkey RM, Goldenberg DM. 
First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 conjugate, Sacituzumab 
Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Clin Cancer Res. 2015 
May 5 [Epub ahead of print]. 
VV-RIM-0003811 1.0 - Approved


Product: IMMU-132 
Protocol: IMMU-132-01 
APPENDIX 1 
List of Standard Treatments for Each Cancer Type 
January 23, 2020 
Refractory to or relapsed after at least one chemotherapy regimen containing one or more 
of the following agents: 5 FU, Cisplatin, Epirubicin, Capecitabine, Irinotecan, Oxaliplatin, 
Vinorelbine; Commonly used standard regimens in the appropriate lines of treatment are 
listed below. 
Epirubicin + Cisplatin + 5-FU (ECF) 
Epirnbicin + Cisplatin + Capecitabine (ECX) 
Epirubicin + Oxaliplatin + 5-FU (EOF) 
Epirubicin + Oxaliplatin+ Capecitabine (EOX) 
Capecitabine + Oxaliplatin (CAPOX, XELOX) 
Cisplatin / Carboplatin + Paclitaxel 
Gemcitabine + 5 FU + Leucovorin 
Liposomal Doxornbicin + Cisplatin + 5 FU 
5-FU + Leucovorin + Oxalipla.tin 
5-FU + Leucovorin + Irinoteca.n 
5-FU + Cisplatin 
Docetaxel + Cisplatin 
Docetaxel + Irinotecan 
Cisplatin + Irinotecan 
Mitomycin + Irinoteca.n 
Paclitaxel / Docetaxel 
Irinotecan 
Vinorelbine 
Etoposide 
Tra.stuzumab 
Erlotinib 
CONFIDENTIAL 
VV-RIM-0003811 1.0 - Approved 
Page 59 of79 


Product: IMMU-132 
Protocol: IMMU-132-01 
Head and neck cancer 
January 23, 2020 
Refractory to or relapsed after at least one chemotherapy regimen containing one or more of the 
following agents: 5 FU, platinum agents, taxanes, gemcitabine, Epimbicin, ifosphamide,bleomycin, 
methotrexate, Ed otinib and cetuximab; Commonly used standard regimens in the appropriate lines of 
treatment are listed below. 
Cisplatin or Carboplatin + 5 FU + Cetuximab 
Cisplatin or Carboplatin + Cetuximab 
Cisplatin or Carboplatin + docetaxel or paclitaxel 
Paclitaxel + Cetuximab 
Docetaxel + Cisplatin + 5 FU (TPF) 
Cisplatin / Carboplatin + 5-FU 
5-FU + Cisplatin + Bleomycin 
5-FU + Cisplatin + Bleomycin + Epimbicin 
5-FU + Cisplatin + Bleomycin + Epimbicin + Mitomycin 
Cisplatin + Docetaxel + Edotinib 
Cisplatin + Gemcitabine 
Cisplatin + Edotinib 
Cisplatin 
Carboplatin 
Oxaliplatin 
5-FU 
Docetaxel 
Paclitaxel 
Gemcitabine 
Ifosphamide, 
Bleomycin, 
Methotrexate 
Cetuximab 
CONFIDENTIAL 
VV-RIM-00038 11 1.0 - Approved 
Page 60 of79 


Product: IMMU-132 
Protocol: IMMU-132-01 
January 23, 2020 
.. 
<J = 
c,: 
<J = 
0 
0 u 
Refractory to or relapsed after at least one Fluoropyrimidine-based, platinum-based or Taxane-
based single agent, doublet or triplet regimen. The chemo regimen may include one or more of 
the following agents: Epirubicin, Cisplatin, Oxaliplatin, 5FU, Irinotecan, Paclitaxel, 
Capecitabine, and Methotrexate. Commonly used standard regimens in the appropriate lines of 
treatment are listed below. 
Epirubicin + Cisplatin + 5-FU (ECF) 
Epirubicin + Cisplatin + Capecitabine (ECX) 
Epirubicin + Oxaliplatin + 5-FU (EOF) 
Epirubicin + Oxaliplatin + Capecitabine (EOX) 
Docetaxel + Cisplatin + 5-FU (DCF) 
Docetaxel + Cisplatin 
Paclitaxel + Cisplatin 
5-FU + Leucovorin + Irinotecan (FOLFIRI) 
5-FU + Leucovorin + Oxaliplatin (FLO) 
5-FU + Leucovorin + Oxaliplatin (FUFOX) +Cetuximab 
5-FU + Doxorubicin + Methotrexate (FAMTX) 
5-FU + Cisplatin 
5-FU + Leucovorin + Irinotecan 
Capecitabine 
Cisplatin + Capecitabine 
Cisplatin + Irinotecan 
Irinotecan + Docetaxel + Oxaliplatin 
Refractory to or relapsed after at least one chemotherapy regimen containing one or more of 
the following agents: 5 FU, Leucovorin, Capecitabine, Irinotecan, Oxaliplatin, Bevacizumab, 
Cetuximab and Panitumumab; Commonly used standard regimens in the appropriate lines of 
treatment are listed below. 
5-FU + Leucovorin + Oxaliplatin (FOLFOX) 
FOLFOX4 + Bevacizumab /Cetuximab 
FOLFOX6 + Bevacizumab 
mFOLFOX6 ± Bevacizumab /Panitumumab 
5-FU + Leucovorin + Oxaliplatin (FUFOX) 
5-FU + Leucovorin + Irinotecan (FOLFIRI) 
5-FU + Leucovorin± Bevacizumab 
FOLFIRI + Bevacizumab 
FOLFIRI + Cetuximab /Panitumumab 
5-FU + Leucovorin + Oxaliplatin+ Irinotecan (FOLFOXIRI) 
Capecitabine + Oxaliplatin (CAPOX, XELOX) 
Capecitabine + Oxaliplatin Irinotecan (COI) 
Capecitabine + Irinotecan (XELIRI) 
Capecitabine + Irinotecan (XELIRI)+ Bevacizumab 
Capecitabine + Oxaliplatin (XELOX) + Bevacizumab 
Capecitabine ± Bevacizumab 
Irinotecan + 5-FU + Leucovorin (IFL) 
Irinotecan + 5-FU + Leucovorin (IFL) + Bevacizumab 
Irinotecan + Oxaliplatin (IROX) Irinotecan ± Cetuximab 
Cetuximab / Panitumumab 
Cetuximab +Bevacizumab + Irinotecan (CBI) 
Cetuximab +Bevacizumab (CB) 
Uracil +Tegafur + Leucovorin 
CONFIDENTIAL 
Page 61 of 79 
VV-RIM-00038 11 1.0 - Approved 


Product: IMMU-132 
Protocol: IMMU-132-01 
January 23. 2020 
Refractory to or relapsed after at least one treatment with the following Fluoropyrimidine-based 
or Platinum based chemotherapy regimens with or v.iithout biological agents or chemo-radiation. 
Commonly used standard regimens in the appropriate lines of treatment are listed below. 
5 FU + Leucovorin ± Bevacizumab 
FOLFOX± Bevacizumab /Panitumumab 
Capecitabine ± Bevacizumab 
.. 
Capecitabine + Oxaliplatin (CapOX) ± Bevacizumab !Panitumumab 
<I,) 
FLOX 
CJ = 
FOLFIRI ± Cetuximab !Panitumumab /Bevacizumab 
c,: 
CJ -; 
FOLFOXIRI 
-
Irinotecan 
CJ 
<I,) 
0:: 
Irinotecan + Oxaliplatin (IROX) 
Irinotecan + Cetuximab !Panitumumab 
Cetuximab !Panitumumab 
5-FU + Leucovorin + Radiation Therapy (RT) 
5-FU + Oxaliplatin + RT 
5-FU +RT 
Capecitabine + RT 
XELOX+RT 
Refractory to or relapsed after at least one of the following chemotherapeutic/targeted agents 
c,: 
and underwent locoregional approaches including trans-arterial chemo-embolization or radio-
s 
embolization. Collllllonly used regimens as the appropriate lines of treatment are listed below: 
0 = 
·.::; .. 
Sorafenib 
c,: 
CJ 
Capecitabine 
.. 
.! 
Doxombicin 
.E 
Bevacizumab 
CJ 
I 
5-FU + Leucovorin 
0 -
c,: 
Capecitabine + Oxaliplatin (XELOX) 
Q. 
<I,) 
:I: 
Cisplatin + Gemcitabine 
Gemcitabine + Oxaliplatin + Bevacizumab (GEMOX-B) 
CONFIDENTIAL 
Page 62 of79 
VV-RIM-0003811 1.0 - Approved 


Product: IMMU-132 
Protocol: IMMU-132-01 
 
 
                             
January 23, 2020                         
 
CONFIDENTIAL 
Page 63 of 79 
 
Ovarian cancer 
Refractory to or relapsed after at least one treatment with platinum based and Taxane based 
doublets/Pegylated Doxorubicin or Gemcitabine or Topoisomerase inhibitor - based regimen or 
biological agents.   Commonly used regimens as the appropriate lines of treatment are listed 
below: 
Carboplatin + Paclitaxel  
Cisplatin + Paclitaxel  
Carboplatin + Gemcitabine  
Pegylated liposomal Doxorubicin 
Pegylated liposomal Doxorubicin + Gemcitabine, alternating with  
Cisplatin + Cyclophosphamide 
Cyclophosphamide + Bevacizumab 
Topotecan 
Etoposide 
Gemcitabin 
Vinorelbine  
 Ifosfamide  
 5-FU + Leucovorin 
 Bevacizumab 
Non-small cell lung cancer 
Refractory to or relapsed after at least one treatment with chemotherapy regimen containing one 
or more of the following agents: Paclitaxel, Docetaxel, Gemcitabine, Pemetrexed, Vinorelbine, 
Topotecan, Erlotinib, Sunitinib, Cetuximab and anti-PD-1 antibody.  Commonly used regimens 
include 
platinum- based doublets, Taxane- based / Pemetrexed, Gemcitabine-based / 
Vinorelbine-based regimens and targeted agents as listed below. 
Cisplatin + Paclitaxel 
Cisplatin + Gemcitabine 
Cisplatin + Docetaxel 
Carboplatin + Paclitaxel 
Carboplatin + Docetaxel 
Carboplatin + Gemcitabine 
Cisplatin + Vinorelbine 
Carboplatin + Vinorelbine 
Gemcitabine + Docetaxel 
Gemcitabine + Vinorelbine 
Carboplatin + Pemetrexed 
Cisplatin + Pemetrexed 
Carboplatin + Paclitaxel + Bevacizumab 
Paclitaxel + Carboplatin + Gemcitabine 
Cisplatin + Gemcitabine + Bevacizumab 
Cisplatin + Vinorelbine + Cetuximab 
Docetaxel + Bevacizumab 
Pemetrexed + Bevacizumab 
Erlotinib + Bevacizumab 
Gefitinib ± platinum doublet chemotherapy 
 
 
VV-RIM-0003811 1.0 - Approved


Product: IMMU-132 
Protocol: IMMU-132-01 
 
 
                             
January 23, 2020                         
 
CONFIDENTIAL 
Page 64 of 79 
 
Urothelial Cancer 
Small cell lung cancer 
Refractory to or relapsed after at least one platinum-based chemotherapy regimen or one of 
the following combinations; Commonly used regimens as the appropriate lines of treatment 
are listed below: 
Cisplatin 
Cisplatin + Etoposide (EP) 
Carboplatin + Etoposide (EP) 
Irinotecan + Cisplatin 
Irinotecan + Carboplatin 
Cisplatin / Carboplatin + Etoposide + Ifosphamide 
Cisplatin / Carboplatin + Etoposide + Paclitaxel 
Cyclophosphamide + Adriamcycin + Vincristin ( CAV) 
Pancreatic cancer 
Refractory to or relapsed after at least one Gemcitabine-based or Fluoropyrimidine-based 
chemotherapy with or without targeted agents.  Commonly used regimens as the appropriate 
lines of treatment are listed below: 
Gemcitabine 
Gemcitabine + Capecitabine (GEM-CAP) 
Gemcitabine + Docetaxel + Capecitabine (GTX) 
Gemcitabine + Oxaliplatin 
Gemcitabine + Erlotinib 
Gemcitabine + Cisplatin 
Capecitabine + Erlotinib 
Oxaliplatin + 5-FU + Leucovorin (OFF) 
5-FU + Leucovorin + Oxaliplatin+ Irinotecan (FOLFIRINOX) 
Abraxane (nab-pacltitaxel) 
Renal Cell Cancer 
Refractory to or relapsed after at least one treatment with a regimen containing one or more of 
the following targeted agents and or immunotherapeutic agents.  Commonly used regimens as 
the appropriate lines of treatment are listed below: 
Sorafenib 
Sunitinib 
Temsirolimus 
Everolimus 
Interferon α-2b 
Interleukin-2 
Interleukin-2 + Interferon α-2a 
Bevacizumab 
Bevacizumab + Interferon α-2a 
Refractory to or relapsed after at least one treatment with a regimen containing one or more 
of the following chemotherapeutic agents.  Commonly used regimens as the appropriate 
lines of treatment are listed below: 
 
Gemcitabine + Cisplatin 
Methotrexate (MTX) +Vinblastine + Adriamycin+ Cisplatin (MVAC) 
Carboplatin or Taxane based regimens 
Cisplatin 
Cisplatin + RT 
Cisplatin + 5 Fu 
Carboplatin + Paclitaxel  
Gemcitabine + Paclitaxel 
Gemcitabine + Cisplatin + Paclitaxel 
Mitomycin + 5 FU  
Pemetrexed 
 
VV-RIM-0003811 1.0 - Approved


Product: IMMU-132 
Protocol: IMMU-132-01 
January 23, 2020 
I-
"" = 
"" 
Refractory to or relapsed after at least one chemotherapy regimen 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), Tamoxifen, Goserelin, 
Anastrozole, Letrozole, Exemestane, Fulvestrant, Trastuzumab and Lapatinib. 
Commonly used standard regimens in the appropriate lines of treatment are listed below. 
AC (Doxorubicin + Cyclophospharnide) 
TAC (Docetaxel +Doxorubicin + 
Cyclphosphamide) 
AC followed by Paclitaxel 
AC followed by Docetaxel 
Dose-dense AC followed by Paclitaxel 
TC (Docetaxel + Cyclophospharnide) 
FAC or CAF (Fluorouracil + Doxorubicin + Cyclophophamide) 
FEC or CEF (Cyclophospharnide + Epirubicin + Fluorouracil) 
CMF ( Cyclophospharnide + Methotrexate + Fluorouracil) 
A followed by T followed by C (Doxorubicin followed by Paclitaxel followed by 
Cyclophospharnide) 
FEC followed by T (Docetaxel) 
EC (Epirubicin +Cyclophospharnide) 
AT (Doxorubicin + Paclitaxel / Docetaxel) 
EP (Epirubicin + Paclitaxel) 
Docetaxel + Capecitabine 
GT (Gemcitabine +Paclitaxel) 
Ixabepilone + Capecitabine 
Paclitaxel + Bevacizumab 
Docetaxel + Bevacizumab 
Capecitabine + Bevacizumab 
Eribulin Tamoxifen + Goserelin,± Zoledronic Acid 
Anastrozole + Goserelin ,± Zoledronic Acid 
AC followed by Paclitaxel+ Trastuzumab 
TH Docetaxel + Trastuzumab 
TCH Docetaxel + Carboplatin+ Trastuzumab 
Trastuzumab + Paclitaxel 
Trastuzumab + Anastrozole 
TPC Trastuzumab + Paclitaxel + Carboplatin 
Trastuzumab +Capecitabine 
T rastuzumab + Docetaxel+ Capecitabine 
Lapatinib + Capecitabine 
Lapatinib+ Paclitaxel 
CONFIDENTIAL 
Page 65 of79 
VV-RIM-0003811 1.0 - Approved 


Product: IMMU-132 
Protocol: IMMU-132-01 
 
 
                             
January 23, 2020                         
 
CONFIDENTIAL 
Page 66 of 79 
 
Prostate cancer 
Refractory to or relapsed after at least one regimen containing one or more of the following 
agents: Docetaxel, Mitoxantrone, Cabazitaxel, Sipuleucel-T, Cyclophosphamide, Vinblastine, 
Vinorelbine, Enzalutamide, Abiraterone Acetate, Radium 223, and Andogen Deprivation 
Therapy.  Commonly used standard regimens in the appropriate lines of treatment are listed 
below. 
Docetaxel + Prednisone  
Docetaxel + Estramustine 
Mitoxantrone + Prednisone 
Estramustine + Vinblastine 
Satraplatin + Prednisone 
Estramustine + Cyclophosphamide 
Cabazitaxel + Prednisone 
Sipuleucel-T 
Cyclophosphamide 
Vinblastine 
Vinorelbine 
Cervical Cancer 
Cisplatin  
Cisplatin + 5 FU 
Cisplatin + Paclitaxel  
Paclitaxel, 
Vinorelbine 
Topotecan 
Cisplatin + Topotecan 
Cisplatin + Vinorelbine 
Cisplatin + Gemcitabine 
Endometrial Cancer 
Doxorubicin + Cisplatin 
Cisplatin + Ifosfamide + Mesna (CIM) 
Megesterol Acetate 
Tamoxifen 
Carboplatin 
Paclitaxel 
Topotecan 
Dactinomycin  
Carboplatin + Paclitaxel 
Doxorubicin+ Cisplatin+ Paclitaxel 
Ifosfamide+ Paclitaxel+Mesna 
 
 
VV-RIM-0003811 1.0 - Approved


Product: IMMU-132 
Protocol: IMMU-132-01 
 
 
                             
January 23, 2020                         
 
CONFIDENTIAL 
Page 67 of 79 
 
Glioblastoma 
Multiforme 
Refractory to or relapsed after at least one chemotherapy regimen containing one or more of 
the following agents: 
 
Irinotecan, Temozolomide, Bevacizumab, Everolimus, Carmustine, Lomustine, Fotemustine, 
Procarbazine, Vincristine, Carboplatin and Cisplatin. Commonly used standard regimens in the 
appropriate lines of treatment are listed below: 
 
PCV (Procarbazine, lomustin + Vincristine) 
Temozolomide +RT 
Irinotecan + Bevacizumab 
Carboplatin + Bevacizumab 
Carboplatin + Teniposide 
Cisplatin + Etoposide 
Thyroid  
Cancer 
(Papillary) 
Refractory to or relapsed after at least one regimen containing one or more of the following 
agents: Radioiodine, Sorafenib, Axitinib, Everolimus, Pazopanib, Sunitinib, Vandetanib, 
Cabozantinib, and Lenvatinib. 
Note:  The lists include regimens recommended by the NCCN guidelines as well as used in documented clinical 
trials.  Patients who received other treatment combination may also be eligible for enrollment after obtaining approval 
from the medical monitor. 
 
 
VV-RIM-0003811 1.0 - Approved


Product: IMMU-132 
Protocol: IMMU-132-01 
Percent 
100 
90 
80 
January 23. 2020 
APPENDIX2 
Performance Status Evaluation 
Karnofsky Perfo1·mance Status 
Level 
ECOG* 
Description 
Normal; no complaints, no 
evidence of disease 
0 
Nomial Activity 
Able to can-yon normal activity; 
minor signs or symptoms of disease 
Normal activity with effort; some 
signs or symptoms of disease 
1 
Symptoms but ambulatory 
70 
Cares for self; unable to can-y on 
nonnal activity or do active work 
60 
Requires occasional assistance but 
is able to care for most needs 
2 
In bed < 50% of time 
50 
Requires considerable assistance 
and frequent medical care 
40 
Disabled; requires special care and 
assistance 
Severely disabled; hospitalization is 
3 
In bed::::, 50 % of time 
30 
indicated although death is not 
imminent 
20 
Ve1y sick; hospitalization is 
necessary 
4 
100% bedridden 
10 
Moribund; fatal processes 
progressing rapidly 
Abstracted from: Kamofsky DA, et al., Cancer. 
*ECOG: Eastern 
1948; 1 :634-656 
Cooperative Oncology Group 
CONFIDENTIAL 
Page 68 of79 
VV-RIM-0003811 1.0 - Approved 


Product: IMMU-132 
Protocol: IMMU-132-01 
APPENDIX3 
January 23. 2020 
Procedure for Collection, Storage, and Shipment of Serum Samples 
It is important that serum and not plasma be sent 
Semm Samples Obtained for· 
Minimum Required Semm 
Documentation to be Completed and 
Measurement of: 
Volume for Each Time-point: 
Sent with Samples: 
HAHA (human anti-antibodies) 
l.SmL 
HAHALevels 
IMMU-132 serum levels 
l.SmL 
PK Levels 
/Free SN38 
Conjugate levels 
l.SmL 
PK Levels SN38 conjugate 
A. Collection Schedule: 
As per protocol. 
B. 
Collection, Labeling, Storage and Shipment: 
1. 
Blood for sennn IMMU-132 (PK) and Human Anti-Human Antibody (HAHA) 
concentrations. 
a) Four (4) mL of blood will be drawn into a glass vacutainer with a red stopper. 
b) Allow blood to clot at room temperature. 
c) Refrigerate clotted sample for 30 minutes at 4°C to contrnct the clot. 
d) Centrifuge at 1000 rpm at 4°C for ten minutes to extract additional sennn. 
e) Pipette all sernm but not more than 1.5 mL into a 2 mL screw cap cryotube (to be 
supplied by hmnunomedics). 
f) 
Label each sample using stickers provided by the Sponsor. They must bear the 
following infonnation: 
CONFIDENTIAL 
Timepoint - Sample 
Protocol No.: IMMU-132-01 
Patient Initials: __ _ 
Patient No.: ___ 
-__ _ 
Date Drawn: ______ _ 
Time Drawn: ___ _ 
VV-RIM-00038 11 1.0 - Approved 
Page 69 of79 


Product: IMMU-132 
Protocol: IMMU-132-01 
 
 
                             
January 23, 2020                           
 
CONFIDENTIAL 
Page 70 of 79 
 
2.  Storage 
 
a) Samples should be stored frozen at -20oC or below until time of shipment. 
 
3.  Shipment 
 
a) Samples should be accumulated and shipped at appropriate intervals on a Monday 
or Tuesday. 
 
b)  Log samples  in  on  the  appropriate  Serum  Pharmacokinetics  and/or  HAHA 
Worksheet(s). This paperwork must be included with all specimen shipments. 
 
 
c)  Labeled cryotubes containing serum samples for HAHA and PK evaluation must be 
wrapped with enough absorbent material to absorb all liquid completely in case of 
leakage.  Place wrapped vials in a leak resistant clear pouch or sealable pack. 
 
d)  The specimens must be placed in an insulating (primary) container with dry ice. 
Place the insulated mailer inside a sturdy outer corrugated (secondary) container and 
write, “DIAGNOSTIC SPECIMEN,” on the box. 
 
 
 
If using dry ice to ship specimens, International Air Transport Association (IATA) 
regulations require that the following packaging markings include: 
 
 
“Dry Ice” 
 
 
“UN 1845” 
 
 
Net quantity of dry ice in kilograms 
 
 
Name and address of BOTH the shipper and recipient (An 
air bill does not fulfill this requirement) 
 
 
 
 
Address package with return address to: 
 
 
 
 
 
 
e)  Shipments must be made by Federal Express.  The airway bill number must be 
transmitted to the CRA by phone before shipment of specimens. 
 
 
VV-RIM-0003811 1.0 - Approved
PPD


Product: IMMU-132 
Protocol: IMMU-132-01 
IMMUNOMEDICS®, INC. 
HAHA Levels Worksheet 
January 23. 2020 
Protocol #: IMMU-132-0lPatient Initials: __ _ 
Patient ID #: ___ -__ _ 
F M 
L 
(Site #) (Pt #) 
Return To: 
Fax No. 
--------------
--------
PLEASE INCLUDE A corx OF THIS PAGE WITH EVERY SHIPMENT 
RECORD ONLY THOSE SAMPLES INCLUDED IN THE SHIPMENT 
[ORIGINAL PAGE(S) SHOULD BE RETAINED IN PATIENT BINDER] 
Sampling Times 
Collection 
Date 
(mm/dd/yy) 
Collection Time 
[as 14:20 = 2:20PM) 
Date& Time 
Sample Frozen 
(mm/dd/yy) 
* If samples are shipped separately indicate date each sample was shipped in 
box(es) above. If the multiple samples are shipped on the same date, simply 
indicate the collection information as required for each sample, check the 
shipment date box [ 
and record the date of that shipment below: 
Shipment date: 
CONFIDENTIAL 
Shipped by: 
Send Specimens 
to: 
VV-RIM-0003811 1.0 - Approved 
Shipping date* 
(mm/dd/yy) 
Page 71 of79 


Product: IMMU-132 
Protocol: IMMU-132-01 
 
 
                             
January 23, 2020                           
 
CONFIDENTIAL 
Page 72 of 79 
 
 
 
IMMUNOMEDICS®, INC. 
 
Antibody IgG and Intact Conjugate PK Levels Worksheet 
 
 
Protocol #: IMMU-132-01 Patient Initials:     
  
 Patient ID #:               -               
F M L 
 (Site #)      (Pt #) 
 
Return To:  
 
Fax No.  
 
 
PLEASE INCLUDE A COPY OF THIS PAGE WITH EVERY SHIPMENT 
RECORD ONLY THOSE SAMPLES INCLUDED IN THE SHIPMENT 
[ORIGINAL PAGE(S) SHOULD BE RETAINED IN PATIENT BINDER] 
 
 
 
Cycle #   Dose # 
Sampling Times 
Collection 
Date 
(mm/dd/yy) 
Collection 
Time 
[as 14:20 = 
2:20] PM 
Date 
Sample 
Frozen 
(mm/dd/yy) 
Time 
Sample 
Frozen 
[as 14:20 = 
2:20] PM 
Shipping 
Date* 
(mm/dd/yy) 
(date) 
* If samples are shipped separately indicate date each sample was shipped in box(es) above.  If the multiple samples are ship ped 
on the same date, simply indicate the collection information as required for each sample, check the shipment date box [] and 
record the date of that shipment below: 
Shipment date: 
Shipped by: 
 
 
 
 
 
 
Send Specimens to: 
 
 
 
 
VV-RIM-0003811 1.0 - Approved
PPD
CCI


Product: IMMU-132 
Protocol: IMMU-132-01 
January 23. 2020 
APPENDIX4 
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 
Qualifying Definition 
Measurable 
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 rmn.) • 10mm caliper 
measurement by clinical exam (lesions which cannot be accurately measured v.iith 
calipers should be recorded as non-measurable) • 20llllll by chest X-ray. 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a 
lymph node must be 15rmn in short axis when assessed by CT scan (CT scan slice 
thickness recormnended to be no greater than 5 llllll). At baseline and in follow-up, 
only the sho1t axis will be measured and followed. 
Non-Measurable 
All other lesions, including small lesions (longest diameter < 1 0rmn or pathological 
lymph nodes v.iith 10 to < 15mm sho1t axis) as well as tmly non-measurable lesions. 
Lesions considered tmly non-measurable include: leptomeningeal disease, ascites, 
pleural or pericardia! effusion, inflallllllatory breast disease, lymphangitic involvement 
of skin or lung, abdominal masses/abdominal organomegaly identified by physical 
exam that is not measw·able by reproducible imaging techniques. 
Special considerations regarding lesion measurability: 
Bone lesions, cystic lesions, and lesions previously treated with local therapy require pa1ticular 
comment: Bone lesions: • Bone scan, PET scan or plain films are not considered adequate imaging 
techniques to measure bone lesions. However, these techniques can be used to confnm the 
presence or disappearance 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 are present in the 
same patient, these are prefened for selection as target lesions. 
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 
CONFIDENTIAL 
VV-RIM-0003811 1.0 - Approved 
Page 73 of79 


Product: IMMU-132 
Protocol: IMMU-132-01 
January 23. 2020 
meti·ic notation, using calipers if clinically assessed. All baseline evaluations should be perfo1med 
as close as possible to the ti·eatment staii and never more than 4 weeks before the beginning 
of the treatment. 
Target Lesions. Tai·get lesions ai·e 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 chai·acterizing objective tumor response to ti·eatment as follows: 
Evaluation Criteria Used fo1· Cate2orizin2 Treatment Response of Tar2et Lesions 
Response Cate201-y 
Definition 
Conmlete Response (CR) 
Disaooearance of all target lesions 
Partial Response (PR) 
> 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as 
reference the baseline sum LD 
> 20% increase in the sum of the LD of target lesions, taking as reference the 
Progressive Disease (PD) 
smallest sum LD recorded since the treatment staited or the appearance of one or 
more new lesions. 
Stable Disease (SD) 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for 
PD, taking as reference the smallest sum LD since the treatment started 
Non-Target Lesions. Non-target lesions ai·e 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- tai·get 
lesions to treatment is evaluated on the basis of their presence or absence as follows: 
Evaluation Criteria Used for Cate2orizimz Treatment Response of Non-Tar2et Lesions 
Response Cate2ory 
Definition 
Complete Response (CR) 
Disappeai·ance of all non-target lesions and normalization of tumor mai·ker 
levels initially above upper limits of normal 
Progressive Disease (PD) 
Appearance of one or more new lesions and/or unequivocal progression of 
existing non-target lesions 
Incomplete Response/Stable 
Persistence of one or more non-tai·get lesion(s) or/and maintenance of tumor 
Disease (SD) 
marker level above the normal limits 
New Lesions. New lesions not present at baseline should be recorded at time of occunence. 
Overall Response. 
The overall response is the best response recorded from the start of the 
ti·eatment until disease progression/recun ence (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 ai·e first met. 
In the case of SD, follow-up 
measurements must have met the SD criteria at least once with a minimum interval of at least 6-8 
weeks from study entry 
CONFIDENTIAL 
VV-RIM-00038 11 1.0 - Approved 
Page 74 of79 


Product: IMMU-132 
Protocol: IMMU-132-01 
Target Lesions 
CR 
CR 
PR 
SD 
PD 
Any 
Any 
Non-Target Lesions 
CR 
Incomplete 
response/SD 
Non-PD 
Non-PD 
Any 
PD 
Any 
New Lesions 
No 
No 
No 
No 
Yes or No 
Yes or No 
Yes 
January 23. 2020 
Overall Response 
CR* 
PR 
PR 
SD 
PD** 
PD** 
PD** 
*When evaluation of possible CR depends on distinguishing residual disease from normal tissue, fine needle 
aspirate/biopsy is recommended before confinning the complete response status. 
**Patients without objective evidence of disease progression, but v.iith globally deteriorated health status 
requiring discontinuation of treatment should be classified as having "symptomatic deterioration" at that time, 
with every effo1t 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 recmTent or 
progressive disease is objectively docmnented (taking as reference for progressive disease the 
smallest measurements recorded since the treatment staiied). Stable disease is measured from the 
staii of the treatment until the criteria for progression ai·e met, taking as reference the smallest 
measurements recorded since the treatment staiied. 
CONFIDENTIAL 
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Page 75 of79 


Product: IMMU-132 
Protocol: IMMU-132-01 
 
 
                             
January 23, 2020                         
 
CONFIDENTIAL 
Page 76 of 79 
 
APPENDIX 5 
 
 
Procedure for Collection, Storage, and Shipment of Whole-Blood Sample 
for UGT1A1 Genotyping 
 
Immunomedics will provide shipping boxes with the appropriate materials for collecting the 
sample and shipping it to Immunomedics.  The kit includes: 
 
 (1) Insulated Shipper (Outer Packaging) 
 
 (1) Plastic Shipping Tubes (50 mL secondary containers) + Cap 
 
 (1) Glass Vacutainer Blood Collection tube inside the secondary shipping tube. 
 
 (4) 24-oz Gel Packs (do NOT freeze) 
 
 Bubble Wrap 
 
 Packing List Envelope with instructions and FedEx shipping form and label. 
 
Blood Draw and Packing Instructions: 
The day before: 
 
1.   Place gel packs from each box to be shipped into a refrigerator overnight. 
 
 
Day of the blood draw: 
 
1.   Draw 1 x 2 mL vacutainer tube per patient on a Cycle 1 Day 1 visit. 
 
2.  Label all the tube with Immunomedics study identification number [site ID – patient 
number] 
 
3.   The blood samples can stay at ambient temperatures until loaded into shipping container 
if shipment takes place on the same day. Samples may be stored in refrigerator up to 7 days 
until shipped. These samples are NOT to be frozen before or during shipment 
 
4.  Multiple samples can be batched together per shipping container if shipped within 7 
days. Make sure each sample is labelled appropriately if multiple samples are in a container. 
 
5.   Put the cold gel packs back into the shipping container. Do NOT use dry ice. 
 
 
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Product: IMMU-132 
Protocol: IMMU-132-01 
 
 
                             
January 23, 2020                         
 
CONFIDENTIAL 
Page 77 of 79 
 
6.   Place the vacutainer tube into the 50 mL secondary container and screw the cap back on 
tightly. 
 
7.   Place the secondary container in a biohazard bag and seal the bag. 
 
8.   Place the tube back into the styrofoam holder. 
 
9.   Pack in the bubble-wrap around the tubes to hold in place during transport. 
 
10. Seal up the box and fill out the FedEx form for shipping (Immunomedics will be charged 
for the shipping costs). 
 
11.  Send FedEx Priority Overnight. 
 
 
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Product: IMMU-132 
Protocol: IMMU-132-01 
 
 
                             
January 23, 2020                         
 
CONFIDENTIAL 
Page 78 of 79 
 
APPENDIX 6 
 
 
Tissue Sample Instructions and Worksheet 
Procedure for Submitting Samples for Tissue Testing for IMMU-132 
 
1.   Tissue testing can be done on paraffin embedded tumor biopsies or other paraffin 
embedded archival tissue (e.g. lymph nodes).  Smears, touch preps or other cytology 
specimens are NOT acceptable. 
 
2.  Send the at least 10   unstained histologic sections on positively charged 
immunohistochemistry slides (preferably Vision Biosystems slides) OR paraffin block. 
Your hospital's histology lab is familiar with these terms and should be able to provide 
this material. If paraffin block is sent, any unused sample will be sent back to you. If you 
have any questions, please call the Clinical Research Department below. 
 
3.   Label the samples with the patient’s study identification # and initials and patient’s 
diagnosis. 
 
4.   Notify your CRA that samples are being shipped. Tissue Sample Shipment forms will be 
provided, and a copy of this form should be included with the shipment. 
 
5.   Ship using Federal Express overnight (airbills provided by Immunomedics). 
 
6.  Shippers must also comply with all applicable local, state and federal laws governing 
packing, marking and labeling of shipments of blood and blood products regardless of 
whether they are infectious.   Blood, urine and Biological Substance, Category B (UN 
3373), shipments may not be deposited in a FedEx Express® Drop Box. 
 
7.   Refer to: http://www.fedex.com/us/services/options/dangerousgoods/hidden.html and 
download the “how to pack” attachment. 
 
8.   Clinical Samples That Are Dried and Non-infectious: Dried samples such as dried 
blood, tissue, saliva, hair.  While noninfectious samples of dried blood are not dangerous 
goods and are not required to meet dangerous-goods regulations, they do require special 
packaging that meets FedEx guidelines.     Dried-blood samples on absorbent pads or cards 
for diagnostic testing must be enclosed in watertight plastic bags and shipped in a sturdy 
outer container or commercial envelope.   Samples on glass or plastic slides must be 
adequately cushioned and may be shipped inside a sturdy outer container or flexible-
envelope packaging.  Use of the FedEx Clinical Pak is optional. 
 
9.   Send the samples to: 
c/o Clinical Research 
Immunomedics, Inc. 
300 The American Road 
Morris Plains, NJ 07950 
 
 
 
VV-RIM-0003811 1.0 - Approved
PPD


Product: IMMU-132 
Protocol: IMMU-132-01 
January 23. 2020 
IMMUNOMEDICS®, INC. 
Tissue Sample Worksheet 
Protocol #: IMMU-132-01 
Patient Initials: __ _ 
Patient ID #: ______ _ 
F 
M L 
(Site #) 
(Pt #) 
Patient's Diagnosis and Current Stage: _________________ _ 
Clinical Site to Complete 
Date 
Sample Sent * 
Fed-Ex 
Sample 
Tissue 
( describe the type and amount of 
Date sent 
tracking 
Taken 
sample sent i.e. 5 unstained slides or 1 toIMMU 
number 
paraffin block) 
* Paraffin block is preferred; if slides are being sent, it should be at least 10 unstained slides. 
Results (to be recorded by Immunomedics, Inc.): 
Immunomedics Use Only 
Date Received 
Date of Analysis 
Results 
Comments 
Send Specimens including a copy ofthis fonn to: 
c/o Clinical Research Department 
Immunomedics, Inc. 
Perfo1med By: ----------
300 The American Road 
Morris Plains, NJ 07950 
PPD 
CONFIDENTIAL 
Approval Signature: _______ _ 
Date of Approval: __ -__ 
-
VV-RIM-0003811 1.0 - Approved 
Page 79 of 79 


Signature Page for VV-RIM-0003811 v1.0
Signature Page for VV-RIM-0003811 v1.0
Approval
23-Jan-2020 14:29:46 GMT+0000
Approval
23-Jan-2020 15:00:24 GMT+0000
VV-RIM-0003811 1.0 - Approved
PPD
PPD

SAP_001.pdf: 
Immunomedics, Inc. 
Statistical Analysis Plan, Protocol IMMU-132-01 
27 Febura,y 2019, Version 3.0 
STATISTICAL ANALYSIS PLAN 
A Phase 1/11 Study ofIMMU-132 (hRS7-SN38 Antibody 
Drug Conjugate) in Patients with Epithelial Cancer 
Protocol Number: 
Protocol Version and Date: 
Name of Test Drng: 
Phase: 
Sponsor: 
Analysis Plan Date: 
Analysis Plan Version: 
IMMU-132-01 
24 April 2017 (includes Amendments # 1 through # 11) 
Sacituzumab Govitecan (IMMU-132) 
Phase I/II 
Immunomedics, Inc. 
300 The American Road 
Monis Plains, 004EJ 07950 
IPPD 
Febrnaiy 27, 2019 
Version 3.0 
Confidentiality Statement 
The information contained herein is confidential and the proprieta1y property of 
Inununomedics, Inc. and any unauthorized use or disclosure of such information without 
the prior w-ritt.en authorization oflnununomedics, Inc. is expressly prohibited. 
CONFIDEmIAL 
VV-RIM-0001564 1.0 - Approved 
Page 1 of40 


Protocol Title: 
Protocol Number: 
Sponsor: 
Author: 
Author Signatory: 
PPD 
Sr. iostatistician 
Sponsor Approval: 
Jmmunomedics, Inc. 
Statistical Analysis Plan. Protocol JMMU-132-01 
27 Febura,y 2019, Version 3.0 
APPROVAL SIGNATURE PAGE 
A Phase I/II StudyoflMMU-132 (hRS7-SN38 Antibody Drug 
Conjugate) in Patients with Epithelial Cancer 
IMMU-132-01 
Immunomedics, Inc. 
300 The American Road 
Morris Plains, NJ 07950 
Veristat, LLC 
118 Turnpike Road 
Southborough, MA O t 772 
PPD 
Date: 
'2 7 Feb 201-i 
------------~--~--
By signing this document, I acknowledge that l have read the document and approve of the 
planned statistical analyses described herein. I agree that the planned statistical analyses are 
appropriate for this study, are in accordance with the study objectives, and are consistent 
with the statistical methodology described in the protocol, clinical development plan, and all 
applicable regulatory guidances and guidelines. 
I have discussed any questions I have regarding the contents of this document with the 
biostatistical author. 
I also understand that any subsequent changes to the planned statistical analyses, as 
described herein, may have a regulatory impact and/or result in timeline adjustments. All 
changes to the planned analyses will be described in the clinical study report. 
Sponsor Signatory: 
PPD 
PPD 
---
Sr. Director, Biostatistics 
CONFIDENTIAL 
Page2of40 
VV-RIM-0001564 1.0 - Approved 


Immunomedics, Inc. 
Statistical Analysis Plan, Protocol IMMU-132-01 
27 Feburary 2019, Version 3.0 
 
CONFIDENTIAL 
Page 3 of 40 
REVISION HISTORY 
Version Number 
Version Date 
Summary and Rational of Revision(s) 
First draft (V0.1) 
13Jul2017 
 
Second draft (V0.2) 
02Aug2017 
 
Third draft (V0.3) 
23Aug2017 
 
Fourth draft (V0.4) 
07Sep2017 
 
Fifth draft (V0.5) 
16Oct2017 
 
V1.0 
24Oct2017 
 
V2.0 
14Mar2018 
• 
Final SAP was amended after clinical database lock 
updated to version 2.0. SAP section 1. 
• 
Sample size for the Target mTNBC Population has been 
revised and updated to 108. SAP section 3.4. 
• 
Sample size for patients who received at least 2 lines of 
prior standard chemotherapy for metastatic disease (ie, 
excluding hormonal or other investigational treatment) 
updated to 94. SAP section 3.4. 
• 
Per-Protocol Population definition has been reworded. 
SAP section 4.3. 
• 
Data listing for the efficacy population has been 
updated to 108. SAP section 4.1. 
• 
Patients Disposition category screened/entered into the 
study has been excluded. SAP section 5.1. 
• 
A separate listing of patients registered but did not 
receive study drug has been excluded. SAP section 5.1. 
• 
New text has been added to Percentage of patients with 
dose reduction. SAP section 5.5. 
• 
Planned dose intensity definition has been updated. 
SAP section 5.5. 
• 
Response assessment dates derivation has been 
corrected. SAP section 6. 
• 
Objective response rate definition has been reworded. 
SAP section 6.2. 
• 
Clinical benefit rate definition has been updated and 
corrected. SAP section 6.3. 
• 
Guidelines and specification for Progression 
Assessment and Censoring for Analysis of PFS has 
been updated. SAP section 6.4. 
• 
Duration of Response definition has been updated. SAP 
section 6.6. 
• 
Sensitivity analyses text has been modified. SAP 
section 6.9. 
• 
Treatment-related Grade 3 or higher AEs by SOC and 
PT was removed and on treatment deaths definition has 
been updated. SAP section 7.1. 
• 
Lab baseline definition has been updated. SAP 
section 7.3. 
VV-RIM-0001564 1.0 - Approved


Immunomedics, Inc. 
Statistical Analysis Plan, Protocol IMMU-132-01 
27 Feburary 2019, Version 3.0 
 
CONFIDENTIAL 
Page 4 of 40 
• 
New text has been added for the eDISH figures, 
defining the Horizontal and Vertical lines for 3xULN 
and 2XULN. SAP section 7.3. 
• 
Informed Consent major protocol violation category has 
been removed. SAP section 8. 
• 
New text has been added to clarify derivation of 
Radiation during treatment violation category under 
prohibited medications category of major protocol 
violation. SAP section 8. 
• 
Best Overall Response with Confirmation of CR and 
PR Required table has been updated for the patients 
missing subsequent response. Appendix 12. 
V3.0 
01Feb2019 
• 
Added analyses populations other than the Target 
mTNBC Population based on cancer histology and 
associated efficacy and safety analyses. 
• 
Added additional subgroup analyses for selected 
efficacy and safety endpoints. 
• 
Added safety analyses and definitions of AE of special 
interest. 
• 
Added some additional safety analyses for the Overall 
Safety Population. 
• 
Dose intensity and relative dose intensity definitions are 
clarified and updated. 
• 
The study drug name sacituzumab govitecan is added to 
the SAP. Where IMMU-132 is referred to, in keeping 
consistent with the Protocol, is identical to sacituzumab 
govitecan that may be used in other documents. 
• 
Added operational dates and characteristics such as data 
planned data cut-off date, last patient enrolment date 
and total number of subjects enrolled for final CSR 
analyses. 
• 
Changed the programming spec for swimmer plot. 
• 
 
• 
Moved data handling rules of missing dates from the 
SAP into separate documentation. 
 
 
 
VV-RIM-0001564 1.0 - Approved
CCI


Immunomedics, Inc. 
Statistical Analysis Plan, Protocol IMMU-132-01 
27 Feburary 2019, Version 3.0 
 
CONFIDENTIAL 
Page 5 of 40 
TABLE OF CONTENTS 
1. 
INTRODUCTION ........................................................................................................9 
2. 
STUDY OBJECTIVES ..............................................................................................10 
2.1. 
Primary Objective .......................................................................................................10 
2.2. 
Secondary Objectives .................................................................................................10 
3. 
INVESTIGATIONAL PLAN .....................................................................................11 
3.1. 
Overall Study Design and Plan ...................................................................................11 
3.2. 
Phase I Dose-Escalation .............................................................................................12 
3.3. 
Phase II .......................................................................................................................12 
 
 
4. 
ANALYSIS POPULATIONS ....................................................................................14 
4.1. 
Efficacy Populations ...................................................................................................15 
4.2. 
Safety Populations ......................................................................................................15 
4.3. 
Per-Protocol Population ..............................................................................................16 
4.4. 
Analyses Population Overview...................................................................................16 
5. 
STATISTICAL ANALYSES .....................................................................................19 
5.1. 
Patient Disposition ......................................................................................................19 
5.2. 
Demographics and Baseline Characteristics ...............................................................19 
5.2.1. 
Demographics .............................................................................................................19 
5.2.2. 
Baseline Disease Characteristics ................................................................................20 
5.3. 
Prior Anticancer Therapy ...........................................................................................20 
5.4. 
Concomitant Medications and Medical History .........................................................20 
5.4.1. 
Medical History ..........................................................................................................20 
5.4.2. 
Concomitant Medications ...........................................................................................20 
5.5. 
Exposure to Study Drug and Compliance ..................................................................21 
6. 
EFFICACY ANALYSIS ............................................................................................23 
6.1. 
Best Overall Response ................................................................................................23 
6.2. 
Objective Response Rate ............................................................................................23 
6.3. 
Clinical Benefit Rate ...................................................................................................23 
6.4. 
Progression-Free Survival ..........................................................................................24 
6.5. 
Overall Survival ..........................................................................................................26 
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Immunomedics, Inc. 
Statistical Analysis Plan, Protocol IMMU-132-01 
27 Feburary 2019, Version 3.0 
 
CONFIDENTIAL 
Page 6 of 40 
6.6. 
Duration of Response .................................................................................................26 
6.7. 
Time to Response .......................................................................................................27 
6.8. 
Other Analyses Related to Efficacy ............................................................................27 
6.9. 
Sensitivity Analyses ....................................................................................................28 
 
 
7. 
SAFETY ANALYSIS ................................................................................................30 
7.1. 
Adverse Events ...........................................................................................................30 
7.2. 
Death ...........................................................................................................................32 
7.3. 
Clinical Laboratory Evaluations .................................................................................32 
7.3.1. 
Pregnancy Tests ..........................................................................................................33 
7.4. 
Physical Examination .................................................................................................34 
7.5. 
Vital Signs ..................................................................................................................34 
7.6. 
Electrocardiograms .....................................................................................................34 
8. 
MAJOR PROTOCOL DEVIATIONS .......................................................................35 
9. 
INTERIM ANALYSIS ...............................................................................................36 
10. 
METHODS FOR HANDLING MISSING DATA.....................................................37 
11. 
CHANGES TO THE PLANNED ANALYSES OR THE STATISTICAL 
ANALYSIS SECTION FROM THE PROTOCOL ...................................................38 
12. 
APPENDIX.................................................................................................................39 
 
 
 
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Immunomedics, Inc. 
Statistical Analysis Plan, Protocol IMMU-132-01 
27 Feburary 2019, Version 3.0 
 
CONFIDENTIAL 
Page 7 of 40 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
ADC 
Antibody-drug conjugate 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ASCO 
American Society of Clinical Oncology 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
 
 
BMI 
Body mass index 
BOR 
Best overall response 
CAP 
College of American Pathologists 
CR 
Complete response 
CRF 
Case report form 
CT 
Computed tomography 
CTCAE 
Common Terminology for Adverse Events 
DILI 
Drug-induced liver injury 
DOR 
Duration of response 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eDISH 
Evaluation of drug-induced serious hepatotoxicity 
FDA 
Food and Drug Administration 
HAHA 
Human anti-human antibody 
HR 
Heart rate 
ICR 
Independent central review 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic resonance imaging 
mTNBC 
Metastatic Triple-Negative Breast Cancer 
NCI 
National Cancer Institute 
NSCLC 
Non-small cell lung cancer 
ORR 
Objective response rate 
OS 
Overall survival 
PD 
Progressive disease 
PFS 
Progression-free survival 
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Abbreviation 
Definition 
PK 
Pharmacokinetic 
popPK 
Population Pharmacokinetics 
PP 
Per-protocol 
PR 
Partial response 
PT 
Preferred term 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SCLC 
Small cell lung cancer 
SD 
Stable disease 
SOC 
System organ class 
TBL 
Total bilirubin level 
TEAE 
Treatment-emergent adverse event 
TNBC 
Triple Negative Breast Cancer 
TTR 
Time to response 
UC 
Urothelial Cancer 
UGT1A1 
Uridine diphosphate glucuronosyltransferase 1A1 
ULN 
Upper limit of normal 
US 
United States 
WHO 
World Health Organization 
 
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1. 
INTRODUCTION 
Immunomedics, Inc. 
Statistical Analysis Plan, Protocol IMMU-132-01 
27 Febura,y 2019, Version 3.0 
This document is the Statistical Analysis Plan (SAP) for Protocol IMMU-132-01 "A Phase I/II 
Study ofIMMU-132 (hRS7-SN38 Antibody Drng Conjugate) in Patients with Epithelial 
Cancer," which was issued on 24 April 2017 (includes Amendments #1 through #11). 
This SAP provides a comprehensive and detailed description of the strategy, rationale, and 
statistical techniques used to evaluate the specified efficacy and safety endpoints. 
Safety and efficacy data will be presented separately for the metastatic Triple-Negative Breast 
Cancer (mTNBC) Target Population, metastatic non-triple-negative Breast Cancer (mBC) 
population and metastatic Urothelial Cancer (mUC) including urinaiy bladder as specifically 
defined in Section 4, Analyses Population. In addition, safety data will also be presented on all 
patients, inespective of tumor type or IMMU-132 dose received; this population will for the 
remainder of the SAP be refened to as the Overall Safety Population. Whereas patients 
populations with cancer type Small-cell lung cancer (SCLC), Non-small-cell lung cancer 
(NSCLC), Colorectal (CRC), Esophageal cancer (EGC), Endometi·ial cancer (EMC), and 
Pancreatic ductal adenocarcinoma (PDC) will be analyzed separately only for the selected 
efficacy endpoints. 
Subsequently, the SAP is amended (Version 3.0) to include efficacy and safety analyses for 
patient populations (as defined by underlying malignancy) other than the Target mTNBC 
Population, and additional safety analyses for the Overall Safety Population, to be based on data 
from final database lock (DBL) with planned data cut-off date of 1 March 2019, in suppo1t of the 
clinical study repo1t (CSR). Separate phannacokinetic (PK) analysis, popPK and 
immunogenicity plans will detail the PK, popPK and immunogenicity analyses. 
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2. 
STUDY OBJECTIVES 
This is a first-in-man clinical study with the antibody-drug conjugate (ADC), IMMU-132, which 
uses the humanized antibody hRS7 to deliver the topoisomerase I inhibitor, SN-38, directly to 
Trop-2-expressing epithelial tumors. The study has been conducted in 2 Phases. Dose escalation 
in Phase I was designed to determine a maximum acceptable dose and to select cancer types for 
further study in the Phase II expansion cohorts. Phase II continued enrollment with dose levels 
and cancers selected based upon Phase I results and preliminary efficacy results. 
2.1. 
Primary Objective 
The primary objective in Phase I is to identify the maximum acceptable dose and 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 cancers. The primary objective in Phase II 
is the evaluation of the safety and efficacy of IMMU-132 administered in 3-week treatment 
cycles, at a dose selected in Phase I. 
2.2. 
Secondary Objectives 
In Phase I, the secondary objectives are to obtain initial data concerning PK, immunogenicity, 
and efficacy with this dosing regimen. In Phase II, secondary objectives also include PK and 
immunogenicity. 
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3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
IMMU-132-01 is a Phase I/II, open-label, basket design study ofIMMU-132 in adult patients 
with epithelial cancers expressing Trop-2. The allowed cancer types include ovarian, 
endometrial, ce1vical, breast (Triple-Negative Breast Cancer [TNBC] and non-TNBC), prostate 
(ho1mone refracto1y), lung (non-small cell and small-cell lung [NSCLC and SCLC], head and 
neck (squamous cell), esophageal, gastric, hepatocellular, renal (clear cell), thyroid, glioblastoma 
multifo1me, colorectal, pancreatic, and urothelial cancers (UC). Eligible patients were required to 
have metastatic (Stage IV) disease at the time of study entiy ( except for glioblastoma 
multifo1me) and be refracto1y to or have relapsed after at least 1 prior standard therapeutic 
regimen for their disease. All patients received IMMU-132 administered IV as a single agent in 
3-week ti·eatment cycles (Days 1 and 8 of21-day cycles). Patients were to continue u-eatment 
until disease progression requiring discontinuation of ti·eatment or unacceptable toxicity. A 
protocol-defined dose reduction scheme was in place to manage patients with selected AEs. 
The primary objective of Phase I is to evaluate the safety and tolerability of IMMU-132 in 
patients with advanced epithelial cancers, using a dose escalation design to dete1mine the 
maximlllll acceptable dose. The secondaiy objective of Phase I is to evaluate the PK, 
irmnunogenicity, and preliminaiy effica.cy of IMMU-132. The primary objective of Phase II is 
the evaluation of the safety and efficacy ofIMMU-132 at a dose selected in Phase I, while the 
secondaiy objectives of Phase II also include evaluation of PK and irmnunogenicity. 
Screening/baseline procedures include patient histo1y , physical examination with vital signs and 
peifonnance status evaluation, local histology/pathology review to confom 1 of the epithelial 
cancers listed above, safety laborato1y assessments, and electi·ocardiogram (ECG). TUillor 
imaging was perfonned using conti·ast enhanced computed tomography (CT) or magnetic 
resonance imaging (MRI). Baseline imaging was obtained within 4 weeks of study entiy. 
Blood/samples were collected to test for hlllllan anti-human antibod 
HAHA and uridine 
di hos hate 
ucuronos lti·ansferase lAl UGTlAl 
enot 
e 
During the study, imaging was perfo1med at baseline (ie, within 4 weeks of study entiy) and 
thereafter in 8 weekly inte1vals from the staii ofu-eatment onwards, with confomato1y CT/MRI 
scans obtained 4 to 6 weeks after an initial pa1iial response (PR) or complete response (CR), 
until pe1manent ti·eatment discontinuation. Response assessment was perfonned according to 
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Response assessment was 
peifonned locally, but independent centi·al review (ICR) of the tumor scans was additionally 
obtained for mTNBC patients who had at least 2 prior therapies for metastatic disease, were 
being ti·eated at the 10 mg/kg dose level, and whose local scans demonsti·ated at least 20% 
decrease. ICR of tumor scans was perfo1med by Inti·insic Imaging (Bolton, Massachusetts; San 
Antonio, Texas, US). The details of the independent review were provided in an imaging chaii er 
for the study. 
After ti·eatment discontinuation, patients were to be followed until resolution or stabilization of 
any ti·eatment-related AEs. All patients were followed for smvival eve1y month, which may be 
by telephone with patient or cai·egiver. 
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The safety of patients is assessed based on occmTence of AEs, clinical laborato1y assessments, 
vital signs, and ECGs. 
3.2. 
Phase I Dose-Escalation 
Phase I dose-escalation used a standard 3+ 3 dose escalation design. Three to 6 patients per 
coho1t were to be enrolled in up to 4 planned dose levels, for a planned total number of24 
patients. Based on preclinical studies, 8 mg/kg was selected as the staiting dose. 
3.3. 
Phase II 
In Phase II, after initially enrolled patients were evaluated in each cancer indication selected by 
the Sponsor in up to 2 dose levels to provide additional safety and efficacy data, indications 
showing a promising tumor response were considered adequate evidence of activity for fmt her 
clinical development, which included TNBC, NSCLC, SCLC and UC. After initial review of 
patients treated at both IMMU-132 doses of 8 and 10 mg/kg, 10 mg/kg was selected for fmther 
clinical development. This dose has been received by the majority of patients in this study, 
including the majority of patients with mTNBC. 
The enrollment of patients of the target mTNBC population was stopped on 14 Febrnaiy 2017 
since the enrollment goals were met after a total of 148 mTNBC patients had been entered, but 
the enrollment of patients in other cancer indications continued. Subsequently, in June 2017, the 
Sponsor notified the sites of the decision to stop fmt her enrollment of patients into the study, and 
the last patient enrolled occmTed on 22 June 2017. 
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4. 
ANALYSIS POPULATIONS 
Given that this study was conducted as a Phase I/Phase II and included a diverse population 
comprised of patients with different tumor types, it is necessary to define specific patient 
populations. The following sections outline the populations to be included for the evaluation of 
efficacy and safety. The patient populations to be used are: 
• Target mTNBC Population: Patients with relapsed/refractory mTNBC who have received 
at least 2 prior therapies for metastatic disease and who received IMMU-132 at a dose of 
10 mg/kg. 
• Per-Protocol (PP) Population (specific to the Target mTNBC Population): This will 
include patients of the Target mTNBC Population who received at least 1 complete cycle 
of IMMU-132 and had data available from at least 1 response assessment. 
• Overall Safety Population: This will include all patients who received at least 1 dose of 
IMMU-132, irrespective of dose, tumor type, or number of prior therapies. 
At the time of final SAP (version 3.0), the following patient populations are added for safety and 
efficacy analyses: 
• Metastatic, non-triple-negative breast cancer (mBC) Population: This will include all 
patients with hormone receptor-positive/human epidermal growth factor receptor 
2-negative (HR+/HER2-) metastatic breast cancer (mBC) who progressed on at least 1 
prior hormonal therapy in the metastatic setting and who received at least 1 dose of 
IMMU-132 at a dose of 10 mg/kg. 
• Metastatic Urothelial cancer including urinary bladder (mUC) Population: This will 
include all mUC patients who had relapsed after or were refractory to at least 1 prior 
standard therapeutic regimen and who received at least 1 dose of IMMU-132 at a dose of 
10 mg/kg. 
And the following patient populations are added for limited efficacy analyses: 
• Small-cell lung cancer (SCLC) Population: This will include all SCLC patients as 
enrolled in the study in accordance with the eligibility criteria and who received at least 1 
dose of IMMU-132. 
• Non-small-cell lung cancer (NSCLC) Population: This will include all NSCLC patients 
as enrolled in the study in accordance with the eligibility criteria and who received at 
least 1 dose of IMMU-132. 
• Colorectal (CRC) Population: This will include all CRC patients as enrolled in the study 
in accordance with the eligibility criteria and who received at least 1 dose of IMMU-132. 
• Esophageal cancer (EGC) Population: This will include all EGC patients as enrolled in 
the study in accordance with the eligibility criteria and who received at least 1 dose of 
IMMU-132. 
• Endometrial cancer (EMC) Population: This will include all EMC patients as enrolled in 
the study in accordance with the eligibility criteria and who received at least 1 dose of 
IMMU-132. 
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• 
Pancreatic ductal adenocarcinoma (PDC) Population: This will include all PDC patients 
as enrolled in the study in accordance with the eligibility criteria and who received at 
least 1 dose ofIMMU-132. 
For the mTNBC target population of 108 patients, it was ensured that all patients had a minimum 
of 4 months follow-up. This allowed to include at least 2 post-baseline assessments ( except for 
patients who died or discontinued study treatment prior to their second post-baseline scan). 
1 
. 
1 
, 
e actual data 
-
the 
CSR. The cut-off date applies to both the Overall Safety Population and individual cancer 
populations. 
4.1. 
Efficacy Populations 
The analysis populations for efficacy analyses include cancer specific populations as defined in 
Section 4. Only patients who received at least one dose of IMMU-132 will be included in the 
analysis. 
For other cancer-specific analysis populations, efficacy analysis and listings will be conducted 
where applicable. No per-protocol populations or sensitivity analyses are planned for cancer 
types other than m TNBC. 
Data listing will in general be perfo1med on the Overall Safety Population and where applicable, 
also on the cancer specific analysis population. 
4.2. 
Safety Populations 
For the pmposes of summarizing safety data, there will be 4 populations, as follows: 
• 
Target mTNBC Population, as defined in Section 4. 
• 
Metastatic, non-triple-negative breast cancer (mBC) Population, as defined in Section 4. 
• 
Metastatic Urothelial cancer including urinaiy bladder (mUC) Population, as defined in 
Section 4. 
• 
Overall Safety Population, as defined in Section 4 which includes all patients regardless 
of cancer type, regai·dless of number of prior cancer therapies, and regardless of 
IMMU-132 dose as long as the patient received at least 1 dose ofIMMU-132. 
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4.3. 
Per-Protocol Population 
The Per-Protocol Population is defined as the subset of Target mTNBC patients who received at 
least 1 cycle of IMMU-132 and had available data from at least 1 response assessment. The Per-
Protocol Population is specific to the mTNBC patients and mainly used for sensitivity analyses 
of efficacy, and no other cancer specific populations has a similarly defined per-protocol 
population. 
4.4. 
Analyses Population Overview 
Analysis populations will be summarized in this study for relevant safety and efficacy endpoint. 
 an overview of the analyses conducted is shown in Table 1. At 
the time of final analyses to support CSR, requisite analyses 
 
for the Target mTNBC Population will be repeated based on the updated data based on the final 
DBL data cut-off date (the sample size of the Target mTNBC Population still remained the same 
in the updated data). In addition, additional analyses will be conducted for analysis populations 
other than mTNBC, along with analyses for the Overall Safety Population, an overview of the 
analyses is shown in Table 2. 
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Table 1: 
Overview of Analyses and Populations 
 
 
Target mTNBC 
Population 
Overall Safety 
Population 
(N=420
 
 
Per-Protocol Population 
Disposition 
X 
X 
 
Demographics 
X 
X 
 
Prior anticancer therapy 
X 
X 
 
Concomitant medication 
and medical history 
X 
X 
 
Efficacy (ORR, PFS, OS, 
DOR, TTR) 
X 
 
X (only ORR; PFS; OS) 
Sensitivity efficacy 
(ORR, PFS, OS) 
X 
 
 
Exposure 
X 
X 
 
AEs 
X 
X 
 
Deaths 
X 
X 
 
Laboratory 
X 
X 
 
Vital signs 
X 
X 
 
ECG 
X 
X 
 
Subgroups efficacy 
X 
 
 
Subgroups exposure 
X 
X 
 
Subgroups safety 
X 
X 
 
Major protocol deviations 
X 
X 
 
Abbreviations: AE = Adverse event, DOR = Duration of response, ECG = Electrocardiogram, mTNBC = Metastatic 
Triple Negative Breast Cancer, ORR = Objective response rate, OS = Overall survival, PFS = Progression-free 
survival, TTR = Time to response. 
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Table 2: 
Overview of Analyses and Populations for Final Analyses 
 
mBC 
mUC 
 
SCLC, NSCLC, 
CRC, EGC, EMC, 
PDC 
Overall Safety 
Population 
(N=approximately 
495 at final DBL) 
Disposition 
X 
X 
 
X 
Demographics 
X 
X 
 
X 
Prior anticancer therapy 
X 
X 
 
X 
Concomitant medication and medical 
history 
X 
X 
 
X 
Efficacy (ORR, CBR, PFS, OS, DOR, 
TTR) 
X 
X 
X 
 
Exposure 
X 
X 
 
X 
AEs 
X 
X 
 
X 
Deaths 
X 
X 
 
X 
Laboratory 
X 
X 
 
X 
Vital signs 
X 
X 
 
X 
ECG 
X 
X 
 
X 
Subgroups analyses * 
X  
X  
 
X 
Major protocol deviations 
X 
X 
 
X 
* Overview of subgroup analyses is provided in Section 6.10, Subgroup Analyses and Section 7.1, Adverse Events. 
Abbreviations: AE = Adverse event, DOR = Duration of response, ECG = Electrocardiogram, mTNBC = Metastatic 
Triple Negative Breast Cancer, ORR = Objective response rate, OS = Overall survival, PFS = Progression-free 
survival, TTR = Time to response. 
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5. 
STATISTICAL ANALYSES 
Throughout this SAP, efficacy data will be summarized for the Target mTNBC Population, 
mBC, mUC, SCLC, NSCLC, CRC, EGC, EMC and PDC Population, with all patients in the 
respective population combined, while safety data will be summarized for the Target mTNBC 
Population, mBC Population, mUC Population and the Overall Safety Population. For the 
Overall Safety Population, data will be summarized by dose group (defined as assigned dose) 
and overall. 
All data will be listed for the Overall Safety Population and where applicable, in the cancer-
specific analysis population, as specified. 
Screen failures and entered-but-not-dosed patients will be excluded from all analyses. 
5.1. 
Patient Disposition 
Disposition in terms of number of patients treated, permanently discontinued treatment, and 
reasons for treatment discontinuation will be summarized for the Target mTNBC Population, 
mBC Population, mUC Population and the Overall Safety Population. 
A by-patient listing for disposition will be provided, including whether the patient is included in 
each of the analysis sets, treatment status, date of stopping treatment, date of stopping study 
participation, reason for treatment discontinuation, reason for study discontinuation, and survival 
follow-up status (ie, date of death, indicator of death during study, and cause of death). 
Patient disposition will also be summarized for the subgroups for selected analyses populations 
as identified and defined in Section 6.10 and Section 7.1. 
5.2. 
Demographics and Baseline Characteristics 
Demographics and baseline disease characteristics for the Target mTNBC Population, mBC 
Population, mUC Population and the Overall Safety Population will be summarized using 
descriptive statistics. Continuous data will be summarized by mean, standard deviation, 
minimum, median, maximum and number of patients. Categorical variables will be summarized 
by frequency tabulations (count, percent) with a separate cell summarizing any missing data 
where applicable. 
Individual patient listings will be provided to support the summary tables. 
5.2.1. 
Demographics 
Baseline demographic data summaries will include age, age group, sex, race, ethnicity, height, 
weight, body mass index (BMI), and number of subjects with renal impairment and hepatic 
impairment. 
Patient demographic data will also be summarized for the subgroups as identified and defined in 
Section 6.10 and Section 7.1. 
Age will be calculated as: Age = Integer ≤ [(Informed Consent Date – Date of Birth + 1) / 
365.25]. 
Body mass index will be calculated as: BMI (kg/m2) = weight in kg / (height in m2). 
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5.2.2. 
Baseline Disease Characteristics 
Baseline disease characteristics will be provided for the target mTNBC Population, mBC 
Population, mUC Population and Overall Safety Population and will include Eastern Cooperative 
Oncology Group (ECOG) performance status, 
 UGT1A1 status, tumor stage at 
initial diagnosis and at screening. In addition, the time since diagnosis of initial cancers will also 
be displayed. 
5.3. 
Prior Anticancer Therapy 
Prior systemic anticancer therapy will be summarized for the target mTNBC Population, mBC 
Population and mUC Population. For the Target mTNBC Population, the number of prior 
anticancer therapies for metastatic disease (2 prior lines vs >2 prior lines) and number of prior 
chemotherapies for metastatic disease (categories: 0, 1, 2, >2) will also be summarized 
categorically. In addition, time since last prior therapy (calculated from the end date of last prior 
therapy to the first dose of IMMU-132) and the duration of last line of prior therapy will be 
summarized. A frequency table will also be produced summarizing chemotherapy, hormonal 
therapy and investigational therapy products separately. For the target mTNBC Population, the 
number of prior anticancer therapies and of prior chemotherapies (excluding investigational and 
hormonal treatments) will also be summarized by the median, minimum and maximum number 
of therapies, and the number of patients. The number of patients receiving each individual 
therapy will also be summarized. 
For mUC Population, the number of prior anticancer therapies, chemotherapies, cisplatin, 
platinum-based chemotherapies, immune check point inhibitors (CPI) including anti-PD1/PDL-1 
therapies will be summarized descriptively and by categories of number of lines of each type of 
therapies. In addition, time since last prior therapy and the duration of last line of prior therapy 
will be summarized. 
For mBC Population, the number of prior anticancer therapies, chemotherapies, CDK4/6 
inhibitors, mTOR inhibitors, hormonal therapies, endocrine therapies, and immune CPIs will be 
summarized similarly descriptively and by number of lines of each type of therapies, along with 
summaries of time since last prior therapy and the duration of last line of prior therapy. 
Additional analyses of prior anticancer therapies of particular interest, if warranted, may be 
generated. 
5.4. 
Concomitant Medications and Medical History 
5.4.1. 
Medical History 
Medical history will be summarized for the Target mTNBC Population, mBC Population, mUC 
Population and the Overall Safety Population, and listed by patient. 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. 
5.4.2. 
Concomitant Medications 
Previous and concomitant medications will be summarized for the Target mTNBC Population, 
mBC Population, mUC Population and the Overall Safety Population and coded using the World 
Health Organization (WHO) Drug Dictionary (WHO Drug Dictionary B3 Enhanced 
March 2017). Medications in this section are distinct from the anticancer medications described 
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previously. These medications will be recorded on the “Pre-infusion medications” case report 
form (CRF) and the “Prior and concomitant medications” CRF rather than the “Prior 
Treatments” CRF. Concomitant medications are those medications that were ongoing at the time 
of first IMMU-132 dose or that were initiated after first dose but prior to last dose. If an end date 
is missing or the medication is ongoing during IMMU-132 treatment, the medication will be 
included as concomitant medication. Reporting of pre-treatment and concomitant medications 
will be by WHO Drug Anatomical Therapeutic Chemical (ATC) Classification. 
Concomitant medical/surgical procedures are defined as therapies that were initiated on/after the 
date of the first dose of study drug and on/before the end of the study treatment period. The 
number (%) subjects who had concomitant medical/surgical procedures will be summarized 
separately in frequency tabulations. 
Additional analyses or listing of concomitant medication of specific interest, if warranted in the 
course of safety review, may be generated. 
5.5. 
Exposure to Study Drug and Compliance 
Treatment exposure will be summarized for the Target mTNBC Population, mBC Population, 
mUC Population and the Overall Safety Population using the following measures: 
• Number of doses administered 
• Duration of treatment (months) 
• Number of patients remaining on the same dose 
• Number of IMMU-132 treatment cycles 
• Percentage of patients with treatment delays 
• Percentage of patients with dose reduction (separately for each category: Any, 1, 2 and 3 
dose reductions) 
• Time to first dose reduction  
• Percentage of patients with permanent treatment discontinuations 
• Percentage of patients with infusion interruptions but completed (based on CRF tick box 
information) 
• Percentage of patients with infusions prematurely discontinued (based on CRF tick box 
information) 
• Duration of patient follow-up (from start of treatment to death, last follow up, study 
discontinuation or data cut-off date) 
Duration of treatment (in days) will be calculated as (date of the last dose – date of the first dose 
+ 1) before being converted to months by dividing it by 30.4375. For patients who are still on 
treatment at the data cut-off date, the date of the last dose will be the latest dosing record end 
date. 
Dose reductions will be calculated by taking the assigned dose level infused for each infusion 
(from the dose administered CRF). From this it will be possible to calculate when a dose 
reduction has occurred and the amount by which the dose was reduced. This will enable the dose 
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reduction, time to dose reduction, and number of patients with a 25% and 50% dose reduction, as 
outlined above to be derived. 
Dose intensity is calculate by the following algorithm: 
Delivered dose (in mg) for each infusion is provided per CRF form. 
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 
dosage (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 
(in 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. 
Patients with treatment delays longer than the 3 weeks permitted in the protocol will be 
summarized by number and percentage of patients. A treatment delay will have been considered 
to have occurred if there are >28 days between Dose 1 and Dose 2 of the same cycle, or >35 days 
between Dose 2 of Cycle n and Dose 1 of Cycle n+1. 
In addition, exposure data will also be summarized for the subgroups as identified and defined in 
Section 6.10 and Section 7.1. 
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6. 
EFFICACY ANALYSIS 
Efficacy results will be summarized for the target mTNBC Population, mBC Population and 
mUC Population. In addition, selected efficacy data will be summarized separately for each 
cancer type populations including SCLC, NSCLC, CRC, EGC, EMC and PDC. Formal statistical 
hypothesis testing will not be performed. Descriptive statistics, data summaries and graphical 
methods will be used to assess the efficacy of IMMU-132. 
The primary endpoint will be the objective response rate (ORR) [PR+CR], with responders 
requiring a confirmatory response assessment no sooner than 4 weeks after the criteria for 
response are first met. Assessment of tumor response is based upon on-site readings by local 
radiologists, using RECIST 1.1 for all populations. Response rates will be additionally provided 
for the Target mTNBC Population and Per-Protocol Population (specific to mTNBC). 
 tumor scans were additionally assessed by independent central review (ICR) 
for mTNBC patients; however, this is not done for other cancer populations. For mTNBC 
population, an ICR was conducted for tumor scans from patients who achieved an objective 
response by local radiologists or at least 20% reduction of their locally determined target lesions. 
Local vs ICR assessments at each response time point and overall will be compared to determine 
concordance of local vs ICR best overall results. An imaging scans time point will be presented 
graphically for the Target mTNBC Population, whether tumor CT scans results were collected 
within allowed time windows at each of the imaging time points (based on 8 weekly imaging 
allowed by protocol and collection windows for study time points that were nominally within 
±10%), based on available data. 
Secondary efficacy endpoints will include time to response (TTR), duration of response (DOR), 
clinical benefit rate (CR+PR+SD [stable disease] ≥6 months), progression-free survival (PFS), 
and overall survival (OS). DOR, PFS, and OS data will be analyzed via Kaplan-Meier method 
and 95% CI from Brookmeyer and Crowley method with log-log transformation. TTR will be 
summarized by descriptive statistics, whilst clinical benefit rate will be presented as a response 
rate along with ORR. 
6.1. 
Best Overall Response 
Response will be determined using RECIST 1.1 criteria, and summarized by the best overall 
response (BOR) using the following hierarchical order: CR, PR, SD, PD, Not evaluable and Not 
assessed. CR or PR will require a confirmation scan. 
6.2. 
Objective Response Rate 
The ORR is defined as the rate of the overall best response as CR or PR. All patients in the 
applicable analysis population will be included in the denominator in the calculation of the 
percentage for each response category and ORR. ORR will be summarized by the percentage of 
responses with 2-sided exact binomial 95% CI. 
6.3. 
Clinical Benefit Rate 
Clinical benefit rate (CR+PR+[SD ≥6 months]) is defined as those patients with best response as 
CR or PR or else SD with a duration of at least 6 months. SD for 6 months duration is defined as 
the time from the first dose to the first documentation of PD or to the last adequate response 
assessment prior to data cut-off date, whichever is earlier. Clinical benefit rate will be 
summarized by the percentage of responses with 2-sided exact binomial 95% CI. 
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6.4. 
Progression-Free Survival 
Immunomedics, Inc. 
Statistical Analysis Plan, Protocol IMMU-132-01 
27 Febura,y 2019, Version 3.0 
Progression-free survival is defined as the interval from the first dose staii date to the date of 
disease progression defined as documented PD or death from any cause, whichever occurs first. 
Death was considered an end point only while the patient was on study and receiving treatment 
or undergoing response assessments. Patients othe1w ise without adequate response assessments 
or without radiologic evidence of progression were censored. Clinical PD was not considered as 
a PFS event. PFS = (Earliest Date of Disease Progression/ Death- First Dose Staii Date+ 1) / 
30.4375. 
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Statistical Analysis Plan, Protocol IMMU-132-01 
27 Febura,y 2019, Version 3.0 
Table 3: 
Guidelines for Response Assessment and Censoring for Analysis of 
Progression-Free Survival 
Guidelines for Progression Assessment and Censoring for Analysis of PFS 
Case 
Outcome 
Date of Event/Censoring1 
No adequate response assessment after start of treatment 
Died prior to second scheduled 
PD 
Date of death 
assessment 
Did not die pdor to second 
Censor 
Date of first dose 
scheduled assessment 
Continued study until objective PD or death 
At scheduled assessment 
PD 
Date of objective PD 
Between scheduled 
PD 
Date of objective PD or death 
assessments 
After missing 2 or more 
Censor 
Date of last adequate response assessment before 
scheduled assessments 
missed ones 
Continued scheduled response assessments without objective PD or death 
Discontinued for 
Censor 
Date of last adequate response assessment 
undocumented PD, toxicity, 
other reasons 
Lost to follow-up 
Censor 
Date of last adequate response assessment 
Initiated other treatment 
Censor 
Date of last adequate response assessment p1ior to 
starting other treatment 
No objective PD at final 
Censor 
Date of last adequate response assessment 
assessment 
Abbreviations: CT = Computed tomography, MRI = Magnetic resonance imaging, PD = Progressive disease, 
PFS = Progression-f ree survival. 
If the onset of response required evaluations at different times (ie, chest CT on 1 day, abdomen and pelvic MRI 
several days late,) the last measurement date was to be used. For PD based on the sum of target lesion 
measurements at different times, the last measurement date was to be used. For PD based on new or non-target 
lesions, if these were equivocal at 1 assessment and later considered unequivocal PD, the earliest date when 
progression was suspected was to be used. 
1 Adequate response assessment was defined as a response assessment other than 'not assessed' or 'not 
evaluable'. As p rogression was based on the sum of target lesion measurements at different time points, the 
last measurement date was to be used. For progression based on new or non-target lesions which ware 
equivocal at 1 assessment but later considered unequivocal PD, the earliest date when progression was 
suspected was to be used. 
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6.5. 
Overall Survival 
Immunomedics, Inc. 
Statistical Analysis Plan, Protocol IMMU-132-01 
27 Febura,y 2019, Version 3.0 
Overall survival is defined as the time from the date of the first dose staii date to the date of 
death due to any cause. Patients without documentation of death at the time of the data cutoff for 
analysis will be censored at the date the patient was last known to be alive or the data cutoff date, 
whichever is eai·lier. The last known alive date is the last record in the study database. This date 
may be the maximum of the last visit date or last contact date, including telephone follow-up 
where the patient is known to be alive. 
6.6. 
Duration of Response 
Among responders (patients who have a best response of PR or CR), DOR will be calculated as 
the date of the first evaluation showing documented PR, or CR to the date of the first PD or 
Death. DOR= (Earliest Date of Progression or Death-Date of First PR/CR + 1) / 30.4375. For 
patients not progressing, censoring mles apply. DOR censoring mles are presented in Table 4. 
Table 4: 
Guidelines for Response Assessment and Censoring for Analysis of Duration 
of Response 
Guidelines for Progression Assessment and Censoring for Analysis of Duration of Response 
Condition 
Case 
Outcome 
Date of Progression or Censo1ing 
At or between scheduled 
PD/ 
Objective PD 
assessments or p1ior to missing 2 
Death 
Date of objective PD or Death 
scheduled successive assessments 
or Death 
Progression or Death after 
occUITed 
Date of last adequate response 
missing 2 or more scheduled 
Censor 
successive assessments 
assessment 
Date of last adequate response 
Initiated other treatment 
Censor 
assessment piior to staiting other 
No objective 
treatment 
PD or Death 
Lost to follow-up 
Censor 
Date of last adequate response 
occUITed 
assessment 
Data cutoff 
Censor 
Date of last adequate response 
assessment 
Abbreviations: CT = Computed tomography, MRI= Magnetic resonance imaging, PD = Progressive 
disease. 
If the onset of response requires evaluations at different times (ie, chest CT on 1 day, abdomen and 
pelvic MRI several days later) the last measurement date should be used. For progression based on the 
sum of target lesion measurements at different times (ie, chest CT on 1 day, abdomen and pelvic MRI 
several days later) the last measurement date should be used. For progression based on new or 
non target lesions, if these are equivocal at 1 assessment and later considered unequivocal progression, 
the earliest date when progression was suspected should be used. If progression occurred after 2 or 
more scheduled successive response assessments were missed or inadequate, the outcome will be 
censored at the last prior adequate assessment. Adequate response assessment is defined as a response 
assessment other than "not assessed" or "not evaluable" for the determination of duration of 
response. If objective evidence of progression has not occurred and the patient is either lost to f ollow-
up, died, a new treatment is initiated, or data cut-off occurs, then the outcome will be censored at the 
last prior adequate assessment. 
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6.7. 
Time to Response 
Time to response is defined as the time from the first dose to the first documentation of response 
(PR or CR). 
6.8. 
Other Analyses Related to Efficacy 
Waterfall plots of the percent change from baseline in target lesion measurement will be 
presented. 
Swimmer plots of onset to response and duration of response will be presented. The plot will 
include only CR and PR patients distinctly color coded; onset of response, response ongoing 
status will be marked at the end of the plot indicating 1) DOR is stopped by PD or death, 2) DOR 
is censored due to missing 2 or more scheduled, initiated of other treatment or loss to follow-up; 
and 3) DOR is ongoing (censored but not due to reasons listed in 2). 
Example of swimmer plot: 
 
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I 
I 
I 
* 
I 
Partial Response 
I 
Complete Response 
Yellow Bar marks onset of response 
Ongoing 
* 
Censored 
0 
2 
3 
4 
5 
6 
7 
8 
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 
Months 


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Statistical Analysis Plan, Protocol IMMU-132-01 
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Example of waterfall plot: 
60 
40 
20 
(l) 
-~ 
ai 
0 
1/) 
ro 
0) 
-20 
E g 
-40 
(l) 
O> 
C: 
ro 
-60 
.c: u 
-80 
-100 
6.9. 
Change in Tumor Size 
ITT Population 
p 
_P - _I\. - A- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
BCR 
C• CR 
R• PR 
S= SD 
Pa PD 
N= NE 
Sensitivity Analyses 
S 
N 
Analyses based on the Per-Protocol Population will be perfo1med for ORR, PFS, and OS for the 
Target m TNBC Population. 
Sensitivity analyses will only be conducted for the Target mTNBC Population, but not planned 
for other cancer-specific analysis population . 
• 
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7. 
SAFETY ANALYSIS 
Safety will be assessed for the Target mTNBC Population, mBC Population, mUC Populations 
and the Overall Safety Population. Data will be presented in terms of AEs, laboratory data, ECG 
data, and vital signs. 
7.1. 
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) Version 20.0 unless 
otherwise specified. The severity will be graded based on the National Cancer Institute’s (NCI) 
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. All AEs will be 
listed. Only TEAEs will be summarized and will be referred to as AEs hereafter. Timing of AEs 
and concomitant medications will take account of the date and the time of the AE or concomitant 
medication. 
The frequency and severity of AEs will be tabulated by MedDRA SOC and PT. For this purpose, 
an AE that occurs more than once within each patient will be counted only once (at the worst 
CTCAE grade and relationship category). Adverse event tables will be sorted by SOC frequency 
and within each SOC, the PTs will be sorted by decreasing frequency for the total IMMU-132 
treated patients’ column reported in each table. 
Additional by-patient listings will be provided for AEs leading to on-treatment death, serious 
AEs (SAEs), and AEs leading to discontinuation of treatment (excluding AEs leading to death). 
Tables summarizing the incidence of AEs will be generated for each of the following: 
1. Overall summary of AEs 
2. All AEs by SOC and PT 
3. Most common AEs (defined as ≥10% of the total number of patients) by PT 
4. Grade 3 or higher AEs by SOC and PT 
5. AEs by SOC, PT, and grade; columns for: any grades; grade 3, grade 4, grade 5 
6. Treatment-related AEs by SOC and PT 
7. Treatment-related grade 3 or higher AEs 
8. SAEs by SOC and PT 
9. Treatment-related SAEs by SOC and PT 
10. AEs leading to permanent treatment discontinuation by SOC and PT 
11. AEs leading to dose interruption by SOC and PT 
12. AEs leading to on-treatment death by SOC and PT, where AEs leading to death is defined 
as any event of grade 5 and/or outcome equal to fatal, and on-treatment death is defined 
as date of death within 30 days of last dose 
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All TEAEs by SOC/PT and the overall TEAE summary table for the following subgroups will be 
provided when the numbers of patients are deemed sufficient for the Target mTNBC Population 
and for the Overall Safety Population: 
• Age (<50, 50-65, >65 years) 
• Sex (male and female) - only for the Overall Safety Population 
• Race 
• Ethnicity 
• Types of Malignancy according to patient’s eligibility criteria CRF - only for the Overall 
Safety Population 
• ECOG Performance Score 
• Renal Impairment (creatinine >ULN; creatinine ≤ULN) 
• Hepatic Impairment, as defined by baseline serum bilirubin: 
- Normal (<=ULN) 
- >1-1.5ULN (> 1 and <= 1.5 x ULN) 
- >1.5ULN (> 1.5 x ULN) 
• UGT1A1 (including but not limited to: *1/*1; *1/*28; *28/*28; not done or missing 
combined in 1 group) 
For the mUC and mBC populations, subgroup analyses of all TEAEs by SOC/PT summary table 
and the overall TEAE summary table will be done for hepatic impairment and UGT1A1 
subgroups, respectively, as defined above. 
For the Overall Safety Population, additional subgroup safety analyses including treatment-
related AEs and SAEs will be summarized by SOC and PT for hepatic impairment and UGT1A1 
subgroups. 
In addition to analyses of AEs, adverse events of special interest (AESI) will be assessed. 
Definitions of AESI, as currently defined, are provided in Table 6, including but not limited to 
listed. For AESI, frequency tables will be generated, showing overall summary of AESI, 
Summary of AESI by SOC and PT, Serious AESI by SOC and PT, AESI leading to 
discontinuation by SOC and PT, AESI leading to treatment interruption by SOC and PT, Grade 3 
or higher AESI by SOC and PT, treatment-related AESI (by a worst CTCAE grade of 3, 4, or 5, 
>=3 and any grade) by SOC and PT. Corresponding listings will also be produced. 
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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 
 
In addition, AESI will be summarized for neutropenia, diarrhea, anemia, nausea and vomiting. 
For each type of AESI, the following will be generated based on the Overall Safety Population: 
• Summary of Subjects with the concerned AESI (by a worst CTCAE grade of 3, 4, or 5, 
>=3 and any grade) 
• Summary of subjects who permanently discontinued treatment due to AESI 
• Time to onset of 1st event of AESI from the 1st dose of study drug and of 1st event of 
AESI or to the 1st event of AESI of Grade 3 or higher; time to onset of event of AESI 
from the time of the dose that is immediately prior to the onset of the AESI event 
• Duration of AESI of any grade, and duration of AESI of grade 3 or higher 
Additional analyses of AEs in general or of specific interest, if warranted in the course of safety 
review, may be generated. 
7.2. 
Death 
All-cause deaths will be summarized (including presentation of death due to PD, AE, or other 
reason) and listed, and deaths within 30 days of the last dose of study drug will be summarized 
for the Target TNBC Population, mBC Population, mUC Population and Overall Safety 
Population. In addition, a listing of death based on patient death report CRF will be provided. 
7.3. 
Clinical Laboratory Evaluations 
Clinical laboratory data results will be reported in standard international units and US 
conventional units. Baseline is defined as the last observation occurring prior to the first 
treatment administration of IMMU-132. Observations occurring on the same day as first 
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treatment day will be the baseline assessment as they are assumed to have occurred prior to the 
time of treatment according to study schedule. 
If a lab value is reported using a non-numeric qualifier (eg, less than [<] a certain value, or 
greater than [>] a certain value), the given numeric value will be used in the summary statistics, 
ignoring the non-numeric qualifier. 
Hematology and serum chemistry data will be listed by patient and summarized by study visit. 
Actual values by visit and change-from-baseline will be summarized by mean, median, standard 
deviation, minimum, maximum and number of patients. 
Shift tables from baseline to worst CTCAE grade on treatment and from worst to last CTCAE 
grade on treatment will be presented where CTCAE grade is available. Shift tables will be 
presented based on CTCAE v4.03 criteria, using the grades 1 through 4 as well as a grade 0 
indicating no abnormality. These shift tables will report the shift from baseline CTCAE grade to 
worst grade on treatment and from worst to last on-treatment visit. 
For liver function tests, summaries of maximum alanine aminotransferase (ALT), maximum 
aspartate aminotransferase (AST), and maximum total bilirubin level (TBL) will be produced to 
evaluate for possible drug-induced liver injury (DILI), including presentation of Hy’s 
law/evaluation of drug-induced serious hepatotoxicity (eDISH) figures (see figure below). For 
the eDISH figures the horizontal and vertical lines for 2ULN and 3ULN will be selected based 
on the lowest available reference range for each parameter. In addition, tables will be produced 
summarizing the number and percentage of patients with multiples of the upper limit of normal 
(ULN) for AST and ALT (≤3 ULN, >3 ULN) and bilirubin (≤2 ULN and >2 ULN) and for 
patients who fulfil either AST or ALT >3 ULN in conjunction with bilirubin >2 ULN. 
 
Patients with elevated ALT or AST (>3 ×ULN) or bilirubin (>2 ×ULN) will be flagged on the 
relevant listing of laboratory data. 
7.3.1. 
Pregnancy Tests 
Pregnancy test results will be listed. 
VV-RIM-0001564 1.0 - Approved
000 
hy 
OnJg X 
100 
OrugC 
10 
01 
10 
100 
100 
T, 
LRR 


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27 Feburary 2019, Version 3.0 
 
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7.4. 
Physical Examination 
A by-patient listing will be presented for any clinically significant findings from the physical 
examination. 
7.5. 
Vital Signs 
The actual value and change from baseline (most recent evaluation within 28 days prior to 
beginning study therapy) to each on-study evaluation, including baseline and end of treatment, 
will be summarized for vital signs. 
Vital sign measurements will be presented for each patient in a by-patient data listing. 
7.6. 
Electrocardiograms 
Descriptive statistics for the actual values and changes from baseline over time will be 
summarized for the ECG parameters including heart rate (HR) measured in beats per minute, 
QTcB and QTcF is not recorded on the CRF page and will be calculated in the following way: 
QTcB = QT/sqrt (RR) and QTcF is calculated as QTcF = QT/cube root of RR interval where 
RR = 60/HR. 
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 the final evaluation on treatment will also be 
provided. 
As ECG comments were collected in a free text field; a listing will also be produced with ECG 
investigator comments in the output (as well as a listing with any investigator comments). 
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8. 
MAJOR PROTOCOL DEVIATIONS 
A by-patient listing with major study protocol violations and deviations will be provided for 
patients in the Overall Safety Population, and major protocol deviations as identified will be 
summarized for the Target mTNBC, mUC, mBC, and Overall Safety Population.  
Protocol Violations to be Programmed 
• Inclusion/Exclusion Criteria 
- <2 weeks between previous treatment, immune therapy, chemotherapy, or 
investigational therapy for metastatic disease and start of treatment with IMMU-132. 
• Prohibited Medication 
- Anticancer therapy during treatment with IMMU-132 (fulvestrant; Gemzar; letrozole; 
nivolumab; paclitaxel; temozolomide). 
- Radiation during treatment with IMMU-132 was not allowed except for pain 
palliation or prophylaxis. 
- Prophylactic medication of hematopoietic growth factors or blood transfusions before 
Cycle 1. 
 
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9. 
INTERIM ANALYSIS 
Analyses based on data from the 30 June 2017 cut-off conducted under SAP version 2.0 
 
 Various administrative interim analyses had been conducted to 
support clinical development decisions or public data disclosures or publications. The final 
analyses are conducted under SAP version 3.0 based on the planned data cut-off date of 
01 March 2019. 
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10. 
METHODS FOR HANDLING MISSING DATA 
Data handling rules, such as imputation rules for missing or partial dates of AE and concomitant 
medication as conventionally applied, and other data handling or programming specifications as 
applied in programming will be specified and documented by a data handling and programming 
specifications document. 
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11. 
CHANGES TO THE PLANNED ANALYSES OR THE 
STATISTICAL ANALYSIS SECTION FROM THE PROTOCOL 
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12.
APPENDIX
Eisenhauer EA, et al. New response evaluation criteria in solid tumours: revised RECIST 
guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026. 
Tumor Response Rules 
Objective Response: Objective responses are evaluated according to RECIST1.1 (Eisenhauer et 
al., Eur J Cancer, 228-247, 2009). Study IMMU-132-01 requires measurable radiologic disease 
at baseline by CT or MRI. Target lesions may include up to 5 measurable lesions (at most 2 per 
organ) selected at baseline and may include pathologic lymph nodes with short axis ≥15 mm. 
The sum of diameters of target lesions uses the longest diameter for lesions that are not lymph 
nodes and the shortest diameter for lesions that are pathologic lymph nodes. Objective tumor 
response for target lesions at each assessment are defined as: 
•
Complete Response (CR): Disappearance of all target lesions. Any pathologic lymph
node must have reduction in short axis to <10 mm.
•
Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as
reference the baseline sum diameters.
•
Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions,
taking as reference the smallest sum on study (which includes the baseline sum if the
smallest on study). In addition to a relative increase of ≥20%, the sum must also
demonstrate an absolute increase of ≥5 mm. (Note: the appearance of 1 or more new
lesions is also considered progression).
•
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient
increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Non-target lesions are other measurable or non-measurable lesions at baseline including 
pathologic lymph nodes with short axis ≥10 mm. Objective tumor response for non-target lesions 
at each assessment are defined as: 
•
Complete Response (CR): Disappearance of all non-target lesions. All pathologic lymph
nodes must be non-pathologic in size (<10 mm short axis).
•
Non-CR/Non-PD: Persistence of 1 or more non-target lesions.
•
Progressive Disease (PD): Unequivocal progression of existing non-target lesions (note:
the appearance of 1 or more new lesions is also considered progression).
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The overall response at each assessment is based on the response of the target and non-target 
lesions, as well as the appearance of any new lesions, as follows: 
Overall Response at Each Assessment 
Target Lesions 
Non-target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all evaluated 
No 
PR 
SD 
Non-PD or not all evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE (inevaluable) 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations: CR = Complete response, PR = Partial response, SD = Stable disease, NE = Not evaluable. 
This study requires confinnation of an overall assessment of CR or PR at least 4 weeks after the 
criteria for response are first met. The BOR across all assessments is determined as follows: 
Best Overall Response with Confirmation of CR and PR Required 
Overall Response 
BEST Overall Response 
Initial 
Subsequent 
CR 
CR 
CR 
CR 
PR 
SD, PD or PR* 
CR 
SD 
SD if minimum criteria for SD duration met, otherwise PD 
CR 
PD 
SD if minimum criteria for SD duration met, otherwise PD 
CR 
Missing 
SD if minimum criteria for SD duration met, otherwise NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD if minimum criteria for SD duration met, otherwise PD 
PR 
Missing 
SD if minimum criteria for SD duration met, otherwise NE 
Abbreviations: CR = Complete response, NE = Not evaluable, PD = Progressive disease, PR = Partial response, 
SD = Stable disease. 
* If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting 
PR c,,iteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after 
CR) . Best response would depend on whether minimum duration for SD was met. However, sometimes 'CR' 
may be claimed when subsequent scans suggest small lesions were likely still present and in fact the patient had 
PR, not CR at the first time point. Under these circumstances, the o,,iginal CR should be changed to PR and the 
best response is PR. 
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