Phase II Pilot Study of Sacituzumab Govitecan for Relapsed Ovarian, Endometrial, and Cervical Carcinomas
Phase: PHASE2
Conditions: Recurrent Platinum Resistant Epithelial Ovarian Carcinoma, Recurrent Epithelial Endometrial Carcinoma, Recurrent Epithelial Cervical Carcinoma
Sponsor: National Cancer Institute (NCI)

Abbreviated Title: SG in gynecologic cancers
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Abbreviated Title: SG in gynecologic cancers  
NIH Protocol #: IRB002068
Version Date: 10/24/2025
NCT Number: NCT06865677
Title: Phase II Pilot Study of Sacituzumab Govitecan for Relapsed Ovarian, Endometrial, and 
Cervical Carcinomas 
NCI Principal Investigator:
Kevin Conlon, M.D., M.S. 
Women’s Malignancy Branch
Center for Cancer Research (CCR)
National Cancer Institute (NCI)
Building 10, Room 3B38
9000 Rockville Pike
Bethesda, MD  20892
Phone:  240-760-6087
Email:  conlonkc@mail.nih.gov  
Drug Name:
Sacituzumab govitecan 
(IMMU-132; Trodelvy)
IND Number:
166593
Sponsor:
NCI Center for Cancer 
Research
Manufacturer:
Gilead Life Sciences, LLC
Supplier
Gilead Life Sciences, LLC

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PRÉCIS 
Background:
•
Human trophoblast cell-surface marker (TROP2) is a surface glycoprotein originally 
identified in human placental tissue and highly expressed in gynecologic malignancies. 
TROP2 overexpression in ovarian, endometrial, and cervical cancers is linked to 
tumorigenicity and poor overall survival. 
•
Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) of an IgGκ1 
monoclonal antibody targeting TROP2 with a chemotherapeutic payload of SN-38. SN-38 
is an active metabolite of irinotecan and acts as a topoisomerase I inhibitor.
•
Preclinical data suggest that SG induces DNA damage, replication stress, and tumor 
shrinkage in drug-resistant ovarian, endometrial, and cervical cancer in vitro and in vivo 
preclinical models. 
•
Further clinical and translational studies are needed to better understand SG’s clinical 
activity and biology in relapsed gynecologic cancer patients.  
Objective:
•
To determine the objective response rate (ORR) of sacituzumab govitecan (SG) in 
participants with recurrent gynecological malignancies, calculated for each individual 
tumor histology by RECIST v1.1.  
Eligibility:
•
Age ≥ 18 years
•
ECOG performance status ≤ 1
•
Histologically documented, recurrent platinum-resistant epithelial ovarian, primary 
peritoneal, or fallopian tube cancer (referred to as ovarian cancer); recurrent endometrioid 
or serous endometrial cancer; or recurrent epithelial cervical cancer
•
At least two prior systemic therapeutic regimens 
•
Measurable disease by RECIST v1.1 criteria with lesions that can be safely biopsied 
•
No prior TROP2-targeting ADC 
Design:
•
This is an open label, non-randomized Phase II pilot study with one Arm. 
•
SG will be administered intravenously (IV) at 10 mg/kg on Days 1 and 8 each 21-day cycle.  
•
Tumor assessments will be time-based: every 9 weeks (± 1 week) for the first year and 
every 12 weeks (± 1 week) thereafter until disease progression. Pre-treatment biopsies and 
serial blood samples will be collected for the correlative studies. 
•
Treatment will be given for a maximum of 5 years or until disease progression or 
unacceptable toxicities. 
•
Up to 66 evaluable participants will be enrolled. 

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Schema 
 

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TABLE OF CONTENTS 
PRÉCIS............................................................................................................................................2
TABLE OF CONTENTS ................................................................................................................4
STATEMENT OF COMPLIANCE ................................................................................................7
1
INTRODUCTION ...................................................................................................................7
1.1
Study Objectives ...............................................................................................................7
1.2
Background and Rationale................................................................................................8
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT .......................................................18
2.1
Eligibility Criteria ...........................................................................................................18
2.2
Recruitment Strategies ....................................................................................................21
2.3
Screening Evaluation ......................................................................................................22
2.4
Participant Registration and Status Update Procedures..................................................24
3
STUDY IMPLEMENTATION .............................................................................................25
3.1
Study Design...................................................................................................................25
3.2
Drug Administration .......................................................................................................25
3.3
On Study Assessments/Evaluations................................................................................30
3.4
Study Calendar................................................................................................................34
3.5
Cost and Compensation ..................................................................................................37
3.6
Criteria for Removal from Protocol Therapy and Off Study Criteria.............................37
4
CONCOMITANT MEDICATIONS/MEASURES...............................................................38
4.1
PROHIBITED MEDICATION.......................................................................................38
4.2
Permitted Medicines/Interventions .................................................................................39
5
CORRELATIVE STUDIES FOR RESEARCH ...................................................................41
5.1
Biospecimen collection...................................................................................................41
5.2
Planned Analyses ............................................................................................................42
5.3
Storage, Use, and Sharing of Specimens and Data (Including for Secondary Research)
44
5.4
Samples for Genetic/Genomic Analysis .........................................................................45
6
DATA COLLECTION AND EVALUATION .....................................................................46
6.1
Data Collection ...............................................................................................................46
6.2
Publication and Data Sharing Policy ..............................................................................47
6.3
Response Criteria ............................................................................................................47
6.4
Toxicity Criteria..............................................................................................................52

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7
NIH REPORTING REQUIREMENTS / DATA AND SAFETY MONITORING PLAN...52
7.1
Definitions.......................................................................................................................52
7.2
OHSRP Office of Compliance and Training / IRB Reporting........................................53
7.3
NIH Required Data and Safety Monitoring Plan............................................................53
8
SPONSOR PROTOCOL/SAFETY REPORTING................................................................53
8.1
Definitions.......................................................................................................................53
8.2
Assessment of Safety Events ..........................................................................................55
8.3
Reporting of Serious Adverse Events .............................................................................55
8.4
Waiver of expedited reporting to CCR ...........................................................................55
8.5
Safety Reporting Criteria to the Pharmaceutical Collaborators......................................55
8.6
Reporting Pregnancy.......................................................................................................56
8.7
Regulatory Reporting for Studies Conducted Under CCR-Sponsored IND...................56
8.8
Sponsor Protocol Deviation Reporting ...........................................................................56
9
CLINICAL MONITORING..................................................................................................57
10
STATISTICAL CONSIDERATIONS ...............................................................................58
10.1
Objectives and Endpoints................................................................................................58
10.2
Statistical Hypothesis......................................................................................................60
10.3
Sample Size Determination.............................................................................................60
10.4
Population for Analysis...................................................................................................60
10.5
Statistical Analyses .........................................................................................................61
11
COLLABORATIVE AGREEMENTS...............................................................................62
11.1
Cooperative Research and Development Agreement (CRADA)....................................62
12
HUMAN SUBJECTS PROTECTIONS.............................................................................62
12.1
Rationale For Subject Selection......................................................................................62
12.2
Participation of Children.................................................................................................62
12.3
Risk/Benefit Assessment.................................................................................................62
12.4
Consent Process and Documentation..............................................................................64
12.5
Study Discontinuation and Closure.................................................................................65
12.6
Quality Assurance and Quality Control..........................................................................65
12.7
Conflict of Interest Policy...............................................................................................66
12.8
CONFIDENTIALITY AND PRIVACY ........................................................................66
13
PHARMACEUTICAL INFORMATION ..........................................................................67

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13.1
SACITUZUMAB GOVITECAN (IMMU-132; Trodelvy) (IND # 166593)..................67
14
REFERENCES ...................................................................................................................68
15
LIST OF ABBREVIATIONS.............................................................................................76
16
APPENDICES ....................................................................................................................80
16.1
Appendix A: Performance Status Criteria ......................................................................80
16.2
Appendix B: Anaphylaxis Precautions ...........................................................................81

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STATEMENT OF COMPLIANCE
The trial will be carried out in accordance with International Council for Harmonisation Good 
Clinical Practice (ICH GCP) and the following: 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812) 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training.
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval. Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled. Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study. In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form.
1
INTRODUCTION
1.1
STUDY OBJECTIVES
1.1.1
Primary Objective
•
To determine the objective response rate (ORR) of sacituzumab govitecan (SG), in 
participants with recurrent gynecological malignancies, calculated for each individual 
tumor histology by RECIST v1.1 
1.1.2
Secondary Objectives
•
To determine the safety of SG
•
To determine the progression-free survival (PFS) of participants receiving SG
•
To determine the overall survival (OS) of participants receiving SG
•
To determine the duration of response (DOR) of SG
1.1.3
Exploratory Objectives
•
To evaluate the concordance (or discordance) of TROP2 expression between archival 
tissues and pretreatment fresh biopsies 
•
To identify baseline characteristics of gene expressions of DNA repair pathways in 
participants with or without clinical response 
•
To identify mutations of TROP2 gene (TACSTD2) in tumors with resistance against SG
•
To investigate systemic pharmacodynamic biomarkers before and after SG treatment (i.e., 
circulating tumor DNA [ctDNA], circulating tumor cells [CTC], and γH2AX expression)
•
To evaluate UGT1A1*28 allele as a predictive marker for gastrointestinal and hematologic 
toxicities

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1.2
BACKGROUND AND RATIONALE
1.2.1
Ovarian Carcinoma
There are several different types of epithelial ovarian carcinoma including high grade serous 
(70%), endometrioid (high and low grade, 20%), clear cell (5%), low grade serous (3%) and other 
rare subtypes (<2%). High grade serous ovarian cancer (HGSOC) is the most common subtype of 
ovarian cancer and the most lethal gynecologic malignancy in developed countries, with 5-year 
survival rate <40% [1]. This unfavorable prognosis is closely related to presentation of the disease 
at late stages, a high (>80%) relapse rate, and intrinsic or acquired resistance to conventional 
chemotherapy. The standard of care treatment includes optimal debulking surgery [2, 3] followed 
by platinum-based chemotherapy. The most commonly used taxane/platinum based 
chemotherapeutic regimen [4, 5] has been well established for some time. These regimens 
produced response rate (RR) in the 60 to 80% rage, with median progression free survival (PFS) 
of about 15 to 20 months and median overall survival (OS) of 30 to 45 months [6, 7] but at least 
75% of these patients will relapse [8]. Attempts to identify alternative regimens with more activity 
have not been successful [9]. Alternatively, patients who are not considered appropriate for 
successful upfront debulking surgery are treated with neoadjuvant combination chemotherapy that 
improves the odds for optimal debulking surgery outcomes and additional adjuvant chemotherapy 
but these patients also relapse at similar rates [10, 11]. 
While the standard adjuvant treatment regimens demonstrated benefit for many patients, durable 
complete responses were uncommon and the search for additional effective agents continued. 
There have been a number of large randomized controlled trials (GOG218, ICON7, OTILLA, 
JGOG3022, ROBOT, ROSiA) assessing the addition of the anti-angiogenic agent bevacizumab to 
the chemotherapeutic regimen in the first line treatment [12-19]. While benefit in terms of 
improvement in PFS, OS, and RR were documented in some of these trials, there was not 
consistent evidence of substantial improvement in these important clinical endpoints. Two clinical 
studies (NCT01847677 and NCT01739218) examining the impact of bevacizumab to standard 
neo-adjuvant chemotherapy showed no improvement in resectability at surgery or other clinical 
endpoints [20, 21]. Three large, randomized trials (NCT00434642, NCT00976911, and 
NCT00565851) assessing the addition of bevacizumab to standard chemotherapeutic regimens not 
all platinum based in the second line [22-24] demonstrated more consistent improvement in the 
clinical endpoint of PFS or OS and sometimes in RR that supports the addition of bevacizumab to 
the standard chemotherapeutic regimens. In addition to being administered as part of adjuvant 
combination chemotherapy regimens, bevacizumab has also been shown to be effective as 
maintenance therapy and as monotherapy in relapsed patients (RR ≈ 15 to 20%) [25, 26].  
As the core chemotherapeutic regimens are nearly all platinum-based, platinum sensitivity is 
generally the most important element in choosing a treatment regimen.  Patients who progress 
during their initial treatment are platinum refractory and are not offered other platinum containing 
regimens. Patients who relapse within 6 months of completing their initial or subsequent platinum-
based regimen are considered platinum resistant and generally are offered a non-platinum regimen. 
Intrinsic or acquired resistance to platinum drugs is the norm for advanced metastatic ovarian 
cancer patients even with the addition of other classes of cytotoxic drugs or anti-vascular 
endothelial growth factor (VEGF) agents [27, 28]. Compared to the other histologic types of 
ovarian cancer, HGSOC initially are very sensitive to platinum containing regimens because of 
underlying homologous repair deficiencies (HRD) present in about 50% of these cancers, 
alterations in p53, and up to 25% of HGSOC have mutations in BReast CAncer gene (BRCA)1 

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and 2 that are mostly germline [29-32]. Because of the high incidence of HRD, HGSOC are also 
very sensitive to poly(ADP-ribose) polymerase inhibitors (PARPi) which are given to platinum 
refractory and resistant patients including as maintenance therapy for patients who achieve 
remissions to their initial or later treatment regimens. 
PARPi have been proven to be an important addition in the treatment of ovarian cancers especially 
HGSOC for the reasons mentioned above. In addition to their role in combination with the standard 
cytotoxic regimens, they have an important role in maintenance therapy for patients with HRD or 
BRCA mutations. But the development of resistance has tempered some of the enthusiasm for 
these agents [33-36].  There are four standard chemotherapeutic drugs (liposomal doxorubicin 
[Doxil®], gemcitabine, paclitaxel, and topotecan) that are commonly given to relapsed or 
refractory ovarian carcinoma sometimes as part of a combination with bevacizumab or as single 
agents. Even in patients with more indolent progressive disease, RR (10 to 15%), PFS (3 to 4 
months), and OS (≈ 12 months) are underwhelming [36, 37], highlighting the unmet medical need 
of novel treatments. 
ADCs are novel therapeutic agents designed to target antigens specific to tumor cells with direct 
delivery of cytotoxic agents while limiting systemic toxicity. The first ADC, mirvetuximab 
soravtansine, was approved for platinum resistant ovarian cancer patients with high folate receptor-
alpha (FRα)-expressing platinum resistant ovarian cancer. Mirvetuximab demonstrated a RR of 
32.4%, including five complete responses (CR), and median duration of response of 5.9 months 
(NCT04296890) [38]. In the confirmatory trial (NCT04209855), the anti-tumor activity of 
mirvetuximab was verified and improved PFS and OS, compared to standard-of-care 
chemotherapy, was reported [39]. Despite these major advances, alternative therapies and novel 
combinations are still needed for patients not eligible to mirvetuximab and those who progress 
after this therapy. 
1.2.2
Endometrial Carcinoma 
Endometrial cancer is the most prevalent gynecologic cancer in the U.S. and usually is low grade 
histology and early stage limited disease at presentation, resulting in a better chance of survival 
[40]. The majority of endometrial cancer is the type I endometrioid endometrial cancer driven by 
obesity and hormonal imbalance and associated with endometriosis [41, 42]. Conversely, serous 
endometrial cancer (SEC; type II endometrial cancer), which comprises ~15% of endometrial 
cancer, exhibits more aggressive phenotypes with a high recurrence rate [43, 44]. High grade 
endometrial carcinoma has been grouped into four molecular subtypes; polymerase ε ultramutated 
(POLEmut), mismatch repair (MMR) deficient, p53 mutant (p53abn) and the 4th group without 
these particular defects referred to as non-specific molecular profile (NSMP) [45, 46]. Like 
HGSOC which is characterized by universal TP53 mutation and DNA repair defects, SEC exhibits 
similar genomic characteristics such as TP53 mutation [47]. Surgical resection is generally the 
standard first therapeutic intervention [48, 49]. Brachytherapy rather than external beam radiation 
with adjuvant or neoadjuvant chemotherapy has been a standard component for the treatment of 
early-stage high risk patients including stage I disease invading more than 50% of the 
myometrium, grade 1 or 2 tumors with lymphovascular space invasion (LVSI) or any lymphatic 
involvement and locally advanced stage III endometrial carcinoma [50, 51]. 
There is evidence that the addition of external beam or brachytherapy to chemotherapy with 
standard platinum/taxane doublets for stage III disease leads to improvements in survival [52, 53]. 
However the recently reported 10-year follow-up for GOG258 (NCT00942357) showed no 

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difference in survival when radiation was added to chemotherapy indicating that the impact on OS 
is still not entirely clear [54] but is appropriate only for a limited number of patients [53]. Even 
with the small percentage of patients initially diagnosed with stage III or IV disease, about 20-25% 
of endometrial cancer patients eventually develop recurrent or metastatic disease [55-57]. Patients 
with locally recurrent disease are treated with surgery, surgery plus radiation therapy, or combined 
modality chemoradiation ± surgery [58, 59]. The initial systemic chemotherapy for metastatic 
disease is most often the standard platinum/taxane doublets sometimes given with a third agent 
(i.e., doxorubicin or bevacizumab for patients with good performance status who are still platinum 
sensitive). Treatment choices beyond these regimens are very similar to the algorithm for HGSOC: 
single agent platinum, taxanes, doxorubicin, liposomal doxorubicin, topotecan or bevacizumab. 
Hormonal therapy with tamoxifen, aromatase inhibitors (AIs), or fulvestrant can have benefit for 
less vigorous patients with more indolent disease [60, 61]. 
Because of the high frequency of PTEN loss, PIK3CA mutation and MMR deficient tumors, 
molecular therapies are given as part of investigational trials with occasional successes. 
Endometrial carcinomas have high level of programmed death-ligand 1 (PD-L1) expression and 
led to testing combinations of immune checkpoint inhibitors (ICI) with other drugs that have 
activity against endometrial carcinoma [62-65] and the combination of lenvatinib (a multi-kinase 
inhibitor including VEGFRs) with pembrolizumab was approved by the Food and Drug 
Administration (FDA) for the treatment of advanced non-microsatellite instability (MSI) high, 
non-MMR deficient endometrial cancer patient who have progressive disease after at least one 
systemic therapy and are not radiation therapy candidates based on the data in KEYNOTE-775 
(NCT03517449) [66]. More recently, anti-programmed cell death protein 1 (PD-1) dostarlimab 
given with carboplatin and paclitaxel was approved for the treatment of endometrial carcinoma in 
patients who are MMR deficient based on the results from the RUBY trial (NCT03981796) [67]. 
Similarly, GY018 trial (NCT03914612) also confirmed the benefit of adding anti-PD-1 
pembrolizumab to carboplatin/paclitaxel in advanced or recurrent endometrial cancer in both 
deficient MMR and proficient MMR cohorts in the randomized phase III registration trial [68]. 
ADCs are now actively investigated as one of the emerging therapeutic options in 
advanced/metastatic endometrial cancer [69]. TROPiCS-03, a Phase II multi-center basket study 
of SG in advanced solid tumors (NCT03964727) [70] reported preliminary clinical data of 20 
patients with endometrial cancer who had prior platinum-based and anti-PD-L1 therapies at the 
2023 ASCO meeting. In 20 patients with ≥13 weeks of follow-up as of 10/11/2022, ORR was 25% 
(95% CI, 8.7-49.1). Clinical benefit rate (CBR; confirmed complete response + partial response 
[PR] + stable disease [SD] ≥ 6 months) was 35% (95% CI, 15.4-59.2). Median PFS was 5.6 months 
(95% CI, 2.3 months-not reached [NR]). Grade ≥3 treatment-related adverse events (TRAEs) 
occurred in 64% of patients; most common grade ≥3 TRAEs were neutropenia (25%), febrile 
neutropenia (14%), and diarrhea (14%). Discontinuation rate due to TRAEs was 7%. Of note, no 
ovarian or cervical cancer patients were included in TROPiCS-03 study and the study is ongoing. 
Despite the recent advances in the standard of care therapy and emerging results from novel 
therapeutics such as ADCs in endometrial cancer, there are still limited understanding of ADC’s 
mechanisms of actions (or resistance) and its impacts on DNA damage response pathways in 
patients.
1.2.3
Cervical Carcinoma 
Cervical cancer is the fourth most frequent cancer in women across the world after breast, 
colorectal, and lung with an estimated 604,127 new cases and 341,831 deaths in 2020 [71]. In 

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2024, it is estimated that there will be 13,820 new cases in the U.S. and an estimated 4,360 people 
will die of this disease [72]. The frontline therapy after initial diagnosis is either surgery or a 
combination of chemotherapy and radiation depending on the stage and the patient factors. 
Although most patients present with early-stage disease, distant metastases or multiple recurrence 
sites develop in 15 to 61% of cases, usually within the first two years after completion of primary 
treatment, and prognosis for recurrent/metastatic cervical cancer still remains poor [73]. 
For women with recurrent/metastatic cervical cancer, the first-line treatment includes platinum-
based chemotherapy and bevacizumab. The addition of bevacizumab to platinum-based doublet 
regimen has shown a survival benefit, leading to the current first-line standard of care based on 
the findings from GOG240 Phase 3 trial. More recently, two Phase 3 studies demonstrated adding 
anti-PD-L1 (GOG3030; atezolizumab [74] [irrespective of PD-L1 status] or KEYNOTE-826; 
pembrolizumab [75] PD-L1 positive disease only] to a standard bevacizumab plus platinum 
regimen significantly improved PFS and OS in metastatic or recurrent cervical cancer and became 
a new first-line therapy. However, despite these advances with combination therapies in cervical 
cancer treatment, there is still compelling need for newer biologic agents due to significant side 
effects and narrow therapeutic window of these drugs. 
Single-agent therapy is generally indicated in the second line setting for patients who progress 
following first-line chemotherapy and those who are not candidates for combination therapy. 
Tisotumab vedotin-tftv is a tissue factor-specific ADC with a microtubule inhibitor approved by 
the US FDA for recurrent or metastatic cervical cancer that has progressed on chemotherapy. In a 
single-arm multi-center Phase II trial (innovaTV204/GOG-3023/ENGOT-cx7; NCT03438396), 
101 patients with recurrent or metastatic cervical cancer who had received no more than two prior 
systemic regimens in the recurrent or metastatic setting were treated with tisotumab. The ORR was 
24% (17% PR and 7% CR) [76]. 
Other ADCs are also actively investigated in advanced/metastatic cervical cancer. Recently, the 
interim analysis from the Chinese multi-center, single-arm phase 2 basket study of SG (EVER-
132-003, NCT05119907) was reported at the 2024 Society of Gynecologic Oncology (SGO) 
meeting. 18 Chinese patients with recurrent/metastatic cervical cancer were enrolled. 
Approximately 80% had prior immunotherapy and two thirds (66%) had at least two prior 
regimens in the recurrent or metastatic setting. ORR was 50% (95% CI, 26%-74%) with a median 
duration of response of 9.2 months (95% CI, 2.9 months-not estimable). Median PFS was 8.1 
months (95% CI, 4.1-10.6 months) in this heavily pretreated population. No new safety signals 
were reported. The accrual for EVER-132-003 study is now ongoing and the verification of data 
is needed. 
1.2.4
Sacituzumab govitecan (SG)
TROP2 is a 36 kDa transmembrane glycoprotein encoded by the TACSTD2 gene that is involved 
in intracellular calcium signaling in many cells. In many cancers including ovarian or endometrial 
carcinomas [77-80], TROP2 overexpression is linked with tumorigenicity and poor OS. TROP2 is 
a trophoblast cell-surface antigen which is overexpressed on many other epithelial tumors [81, 82]. 
TROP2 expression is relatively common in gynecologic malignancies. In a comprehensive tissue 
microarray study with 18,563 tumor samples including HGSOC (n = 344) and endometroid 
endometrial cancers (n = 160), approximately 80-90% of HGSOC and endometrial cancer were 
TROP2 positive [83]. Also, Santin’s group evaluated the primary surgical samples from 147 
cervical cancer patients. Of 147, 113 were squamous cell carcinomas (SCCs), and 34 were 

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adenocarcinoma/adenosquamous carcinomas. Moderate to strong diffuse TROP2 staining was 
seen in 95% (108/113) of SCCs, and 81% (29/34) of adenocarcinoma/adenosquamous cancers on 
immunohistochemistry (IHC) [84]. 
SG is a novel ADC, comprising a topoisomerase 1 (TOP1)–inhibiting camptothecin, SN-38 (7-
ethyl-10-hydroxycamptothecin, the active metabolite of irinotecan, a TOP1 inhibitor), linked to a 
humanized antibody targeting TROP2. SG has a high drug-to-antibody ratio with 7.6 molecules of 
moderately toxic SN-38 conjugated to each antibody via the unique hydrolyzable and proprietary 
linker, CL2A [85]. The linker allows for intratumoral release of therapeutic concentrations of SN-
38, as well as release extracellularly within the surrounding tumor microenvironment, providing a 
bystander effect [85]. 
The TOP1 inhibitors (TOP1is), irinotecan and topotecan are widely used against a broad spectrum 
of malignancies including colon, ovarian, pancreatic, and small cell lung cancers [86]. In 
gynecologic cancers, topotecan is an FDA-approved regimen for women with recurrent ovarian 
and cervical cancers [87] and is one of the recommended drugs for relapsed endometrial cancer 
[88] per National Comprehensive Cancer Network (NCCN) guidelines and showed ~15-20% of 
ORR across the diseases. There are currently 10 ADCs approved by the FDA, and of the three 
approved in the past 3 years, two are ADC-TOP1i including SG and trastuzumab deruxtecan [89]. 
SG’s benefit has been seen in breast cancer and urothelial carcinoma independent of TROP2 
expression, thus no need for a companion diagnostic test for TROP2 expression [90-92]. It is 
noteworthy that most post-hoc TROP2-specific biomarker studies used the archival tissue samples 
and investigated TROP2 expression as prognostic or predictive biomarkers. For instance, an 
exploratory post-hoc subgroup analysis from TROPiCS-02 study revealed SG improved PFS and 
OS across both TROP2 IHC H-score groups (<100 or ≥100) and SG benefit was also seen in ORR, 
CBR, and DOR compared with chemotherapy regardless of TACSTD2 mRNA expression [93]. 
However, it is unclear whether SG can modulate TROP2 expression in patients after treatment. 
1.2.4.1
Preclinical Studies
First, Dr. Jung-Min Lee’s lab (Women’s Malignancy Branch, CCR, NCI) performed flow 
cytometric analysis to determine TROP2 expression in various drug-sensitive and drug-resistant 
ovarian cancer cell lines (Figure 1A, unpublished data). TROP2 was highly expressed in most 
HGSOC cell lines independent of their BRCA mutation or PARPi or platinum resistance status.  
TROP2 expression also was evaluated on RNAseq data from fresh biopsy samples of recurrent 
HGSOC patients who were enrolled in the NCI Phase 2 trial of cell cycle checkpoint inhibitor 
prexasertib (NCT02203513) (Figure 1B, unpublished data). TROP2 was highly expressed in 
HGSOC compared to normal ovary tissues and was not associated with clinical benefit by 
prexasertib, in both BRCA mutant (BRCAmut) and BRCA wild-type (BRCAwt) patients. 

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Figure 1, TROP2 expression. Screening ovarian cancer cell lines for TROP2 expression (A) and RNAseq 
analysis of HGSOC tumors for TROP2 expression (B). Expression values (TPM, Transcripts per million) (Log2) 
for TROP2 (TACSTD2) from both BRCAmut (n = 15) and BRCAwt patients (n = 20) were compared against 
TPM values of TROP2 from normal ovarian tissues (normal) gleaned from the GTEx database (n = 180). TROP2 
values were not associated with clinical benefit (defined by > 6 months PFS) by prexasertib therapy.  * P < 
0.05, ** P < 0.01, and *** P < 0.001; ns, not significant.
Also, Dr. Lee’s lab found that SG monotherapy induces DNA damage and replication stress in 
HGSOC cell lines (Figure 2, unpublished data). Increased percentage of cells with pan-nuclear 
γH2AX and γH2AX foci by IF and elevated levels of γH2AX by immunoblotting were seen upon 
SG treatment in both PARPi-sensitive and PARPi-resistant HGSOC cell lines (Figure 2 A and B). 
Surprisingly this DNA damage was not further enhanced by the addition of an ataxia telangiectasia 
and RAD3-Related (ATR) inhibitor (ATRi) berzosertib. Similarly, increased replication stress 
measured by a DNA fiber assay was observed by SG alone but not augmented by the addition of 
berzosertib to SG in PARPi-resistant HGSOC (Figure 2C). 
In ovarian cancer cell lines, preliminary immunoblotting data showed no significant changes of 
TROP2 levels by SG and/or ATRi treatment, although this requires further validation (data not 
shown). In breast cancer preclinical models, Zhu et al. reported that inhibitors of AKT, RSK, and 
p38 MAPK suppressed the TROP2 expression while tamoxifen treatment significantly increased 
TROP2 expression in luminal breast cancer cell lines [94]. Further studies are needed to better 
understand SG’s impact on target proteins such as TROP2 in patients for the future 
pharmacodynamic studies and combination trials.
A. 
B.

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Figure 2,  Effect of SG and berzosertib on DNA damage (A, B) and replication fork (RF) stability (C). A. 
Representative images of TROP2 positive PEO1 (PARPi-sensitive) and OlaJR (PARPi-resistant) HGSOC cells 
that were pretreated with SG and then exposed to berzosertib (ATRi) (1 µM) overnight. Slides were then probed 
for γH2AX-S139 (pink) and RPA1 (green dots).  Approximately 100–200 cells were analyzed for γH2AX foci and 
counted as pan nuclear (> 15 foci/nucleus) or below (5–15 foci/nucleus) and plotted as bar charts. B. Cells were 
pretreated (30 minutes at 37C) with SG and then exposed to berzosertib (ATRi) overnight at the given 
concentrations. Western blot analysis of downstream proteins of ATR/ATM pathways and DNA double strand 
break marker pH2AX-S139 (γH2AX) is shown. Effect of berzosertib (ATRi), SG or a combination of both on 
γH2AX levels and corresponding effect on ATM activity as measured by activated ATM (pATMS1981) or its 
specific phosphorylated substrate KAP1 are shown. All experiments were performed at least three times with 
similar outcomes. C. DNA fiber assays for studying DNA RF stability was performed as detailed previously. 
About 200 DNA fibers were selected and the length of both red (IdU) and green (CldU) strands were measured 
using Fiji™ software and the ratio of IdU/CldU were plotted as column charts using GraphPad prism®.  
Basically, the lower ratio of IdU/CldU compared to the control indicates a deficit in replication fork protection 
or blocked fork progression.  Representative strands are shown below the corresponding columns.  P values for 
all figures are marked as asterisks. * P < 0.05, ** P < 0.01, and *** PP < 0.001; ns, not significant.
In xenograft studies, SG alone induced tumor shrinkage in both PARPi-sensitive (PEO1-Luc, 
TROP2 positive) and PARPi-resistant (PEO1-olaR-Luc, TROP2 negative) HGSOC mouse 
models, again ATRi berzosertib did not further induce tumor shrinkage (Figure 3, unpublished 
data). As a result of these preclinical findings, Dr. Lee’s group decided to identify the better drug 
candidate for the future combination trials with SG for gynecologic cancer patients and are now 
conducting mechanistic studies with SG in gynecological cancer preclinical models.  

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Figure 3, Mouse studies.  Top: Schematic of treatment strategy for mice treated with single treatments of SG or 
berzosertib (ATRi) or a combination of both. Disease bearing mice (10 per group) were treated with sterile 
saline/PBS, or with SG alone (IP) or with berzosertib (25 µg/gm) (oral gavage) three times a week or a 
combination of both over 4 weeks, with first dose given 24 hours after SG treatment. Mice were imaged on 
Fridays of every week for the duration of the experiment.  Representative images of luciferase imaging of TROP2 
positive PARPi-sensitive PEO1 (Middle) and TROP2 negative PARPi-resistant PEO1 OlaR (Bottom) HGSOC 
xenograft models that show change in disease burden from Day 0 to Day 77, and a line plot of the same data 
from 8-10 mice plotted on the right. P values are shown to the right of vertical parenthesis encompassing relevant 
groups being compared.  P values, * P < 0.05 and ** P < 0.01. 
Santin’s lab also tested SG in other gynecologic cancer preclinical models including uterine 
carcinosarcoma (Figure 4) and cervical cancer (Figure 5). TROP2 positive uterine 
carcinosarcoma cell lines (SARARK4, SARARK9) showed higher sensitivity to SG in vitro when 
compared to TROP2 low/negative (SARARK14) cell lines [95]. In xenografts, SG alone induced 
a significant tumor growth inhibition when compared to control, to ADC control and to the naked 
Antibody (AB) (p=0.004, p=0.007 and p=0.0007, respectively). SG significantly improved OS at 
90 days when compared to control groups (p<0.0001) (Figure 4) [95]. In cervical cancer, SG also 
induced a difference in tumor growth inhibition beginning on day 18 (p < 0.001) in SG-treated 
group and improved OS at 90 days (p = 0.014) when compared to the other control groups in 
TROP2 positive cervical cancer xenografts (CVX8) (Figure 5). Animals tolerated SG treatment 
well with no significant toxicity [95]. It is also noteworthy that SG demonstrated a significant 
bystander killing effect, which could aid in treating tumors with heterogeneous antigen expression. 

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Figure 4, SG monotherapy in endometrial carcinosarcoma xenografts. Antitumor activity (A) and Survival (B) of 
the SG versus controls in TROP2 positive uterine carcinosarcoma (SARARK9) xenografts. Mice were treated twice 
per week for three weeks by IV injection of saline, SG, ADC control, and naked AB (A) SG significantly inhibited 
tumor growth when compared to saline, ADC control, and naked AB beginning at day 7 of the treatment (p=0.004, 
p=0.007 and p=0.0007 respectively). (B) Overall survival at 90 days was significantly improved in the SG group 
(p<0.0001).
Figure 5, SG monotherapy in cervical cancer xenografts. Antitumor activity of SG was compared to controls 
including, CTRL ADC isotype, hRS7 IgG and CTRL saline, in cervical cancer xenograft models (ie, CVX8, 2 + TROP2 
positive) (4 mice per group) All treatments were given twice per week for 3 weeks by intravenous injection of 500 μg 
of SG, control ADC, saline and hRS7 IgG.  (A) Overall survival. (B) Tumor growth inhibition.
These preclinical results combined with the recent Phase II clinical trial data demonstrating 
promising clinical responses in multiple solid tumors that are resistant to chemotherapy, strongly 
support the design of SG clinical trials in recurrent or advanced gynecologic cancer patients.  
1.2.4.2
Clinical Studies
As of April 2024, there are two completed studies of SG for solid tumors and 23 ongoing studies 
of SG with at least one participant enrolled. The final safety and efficacy report of the phase I/II 
basket study (NCT01631552) (n=495) [85] included 18 patients with recurrent/refractory 
endometrial cancer who had relapsed after or were refractory to ≥1 prior standard therapeutic 
regimen. 4 of 19 endometrial cancer patients achieved PRs yielding 22.2% of ORR. Also, the 
interim data from the ongoing TROPiCS-03 phase 2 basket study (NCT03964727) showed 25% 
ORR in endometrial cancer patients.  With respect to cervical cancer, the recent interim analysis 
from Chinese’s multicenter phase 2 basket study of SG (EVER-132-003, NCT05119907) showed 
50% ORR (9/18) in recurrent cervical cancer patients. Also, Santin’s group recently (4Q 2023) 
opened the pilot single arm Phase II trials of SG monotherapy in recurrent/metastatic ovarian 
(NCT06028932), endometrial (NCT04251416) and cervical cancers (NCT05838521); 20 patients 

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per each cohort. The data from these small pilot studies will require confirmation for further 
development of SG. 
Table 1 shows common adverse events (AE)s of SG monotherapy reported in advanced/metastatic 
triple negative breast cancer (TNBC) patients. The most frequent AEs (all grades) included 
gastrointestinal toxicity (diarrhea, nausea/vomiting, abdominal pain, anorexia, constipation), 
fatigue, neutropenia, anemia, and alopecia. Although grade ≥ 3 neutropenia was relatively 
common (34.5%), it was rare to have febrile neutropenia. Other grade 3 or 4 AEs were limited to 
fatigue, diarrhea, anemia, or neutropenia. 
Table 1, Adverse events with SG
1.2.5
UGT1A1 and Mutation for SN-38 Metabolism 
SN-38 (the active metabolite of irinotecan) is metabolized by uridine diphosphate-glucuronosyl 
transferase 1A1 (UGT1A1). Irinotecan-treated subjects who are homozygous for the UGT1A1*28 
allele are at increased risk for neutropenia and diarrhea (Camptosar Prescribing Information, 
2018). Preliminary results from study IMMU-132-01 (NCT01631552) suggest that the frequency 
of some exposure-related AEs (i.e., neutropenia and febrile neutropenia) may be higher in subjects 
homozygous for the *28 allele as well; however, the frequencies of neutrophil count decreased and 
other treatment-related adverse events, notably diarrhea, did not differ among the subgroups. 
Concomitant administration of strong inhibitors or inducers of UGT1A1 with SG should be 
avoided due to the potential to either increase (inhibitors) or decrease (inducers) the exposure to 
SN-38. In the phase I/II basket study (NCT01631552), the influence of UGT1A1 genotype status 
on the incidence of AEs was analyzed in 403 (81.4%) patients for whom UGT1A1 genotypes were 
available [85]. Most patients were either wild type for the UGT1A1 allele (∗1/∗1) or heterozygous 
for the ∗28 allele (∗1/∗28). Only 9.3% (n = 46) were homozygous for the ∗28 allele (∗28/∗28). The 
pattern and incidence of AEs were broadly similar in heterozygous and wild-type patients. 
Neutropenia was numerically more frequent in homozygous patients (28/46; 60.9%) compared 

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with heterozygous (69/180; 38.3%) and wild-type patients (59/177; 33.3%). The frequency of 
diarrhea was generally similar between heterozygous and wild-type patients, although slightly 
higher in homozygous patients (60.9%, 51.7%, and 54.8%, for homozygous, heterozygous, and 
wild-type patients, respectively). Anemia occurred in 50.0%, 31.7%, and 37.3% in homozygous, 
heterozygous, and wild-type patients, respectively. The percentage of patients who permanently 
discontinued treatment for any reason was similar among patients who were either wild type, 
heterozygous, or homozygous, with rates of 98.3%, 96.7%, and 97.8%, respectively. Of note, the 
FDA-approved drug label for Trodelvy (SG) indicates that screening for UGTIA1 testing is 
not required for SG treatment and the dose should be adjusted on the basis of individual 
patient tolerance because the appropriate dose for these patients is unknown [96].
1.2.6
Rationale  
There is an urgent need for the novel therapeutic agents for relapsed gynecologic cancer patients 
because single agent chemotherapy generally yields low ORRs (10-15%) with median PFS of 3-4 
months [25, 26].  
ADCs are currently FDA approved in ovarian (FR alpha-specific ADC) and cervical (TF-specific 
ADC) cancers and are a rapidly emerging class of therapeutic agents, with ongoing research to 
improve outcomes in the various settings of gynecologic cancer. Yet, there is insufficient 
information on the TROP2-sepcific ADC, specifically, SG’s clinical activity and biology in 
heavily pretreated (three or more previous systemic therapies) gynecologic cancer patients, 
underscoring the importance of further clinical and mechanistic translational studies.  
We and others have demonstrated the monotherapy activity of SG in gynecologic cancer 
preclinical models and found that SG alone can induce DNA damage, replication stress, and tumor 
shrinkage in drug-resistant HGSOC preclinical models. While small basket clinical trials are 
currently testing SG in gynecologic malignancies, there is still a need to confirm the clinical 
activity in heavily pretreated gynecologic cancer patients, also to do correlative studies prior to 
moving forward with large randomized clinical trials. Hence, our proof-of-concept Phase II pilot 
study will provide important insights of SG’s activity and biology in patients by studying fresh 
biopsies and serial blood samples. 
In summary, recurrent/metastatic gynecologic cancers are incurable, highlighting the urgent need 
for new therapeutic options. We aim to investigate the clinical activity of SG in heavily pretreated 
patients and to better understand the biology of SG in gynecologic cancer patients, particularly, 
concerning DNA damage repair pathways and TROP2 expression. As several ADCs show promise 
in subsets of gynecologic cancers, continued translational/correlative studies are necessary to 
determine the best therapeutic approaches for SG and to identify the targets for the future 
combination trials.
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT 
2.1
ELIGIBILITY CRITERIA 
2.1.1
Inclusion Criteria 
2.1.1.1
Cohort 1 (Ovarian Cancer)
2.1.1.1.1 Participants must have histologically or cytologically confirmed recurrent platinum-
resistant (defined as less than six months of platinum-free interval) epithelial (i.e., high 

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grade serous, endometrioid, low grade serous, or clear cell) ovarian carcinoma that is 
refractory to standard treatment. 
2.1.1.1.2 Participants with known BRCA mutated tumors should have received a PARP inhibitor 
maintenance or treatment.
2.1.1.1.3 Participants without known BRCA mutation and platinum-resistant tumors must have 
had prior bevacizumab or not eligible for bevacizumab-based therapy (i.e., history of 
proteinuria).
2.1.1.2
Cohort 2 (Endometrial Cancer)
2.1.1.2.1 Participants must have histologically or cytologically confirmed recurrent epithelial 
(i.e., endometrioid or serous) endometrial carcinoma that is refractory to standard 
treatment. 
2.1.1.2.2 Participants must have received prior anti-PD-1/PD-L1-based therapy or not eligible for 
anti-PD-1/PD-L1-based therapy. 
2.1.1.3
Cohort 3 (Cervical Cancer) 
2.1.1.3.1 Participants must have histologically or cytologically confirmed recurrent epithelial 
cervical (i.e. squamous or adeno) carcinoma that is refractory to standard treatment. 
Note: Participants with a history of human papilloma virus infection (i.e., positive HPV 
DNA testing) are eligible.
2.1.1.3.2 Participants must have received prior bevacizumab-based therapy or not eligible for 
bevacizumab-based therapy (i.e., history of proteinuria). 
Note: Platinum chemotherapy administered concurrent with primary radiation (i.e., 
weekly cisplatin) is not counted as a systemic chemotherapeutic regimen for 
management of persistent or recurrent carcinoma of the cervix.
2.1.1.4
All Cohorts
2.1.1.4.1 Participants must have received at least two systemic therapies including at least one 
platinum-based therapy regimen. 
2.1.1.4.2 Participants must have radiographically measurable disease, per RECIST 1.1, and safely 
biopsiable lesion. 
2.1.1.4.3 Age ≥ 18 years 
2.1.1.4.4 ECOG performance status ≤ 1 (see Appendix A: Performance Status Criteria)
2.1.1.4.5 Adequate organ and marrow function as defined below:
•
Hemoglobin (Hgb) ≥ 9.0 g/dL
•
Absolute neutrophil count (ANC) ≥ 1,500/mcL
•
Platelets ≥ 100,000/mcL 
•
White Blood Cell count (WBC) ≥ 3,000/mcL
•
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤ 3 x ULN in participants 
with known/suspected Gilbert’s disease)

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•
Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 2.5 x 
ULN 
•
Serum creatinine ≤ 1.5 x ULN or   estimated GFR ≥ 30 ml/min/1.73 m2 
2.1.1.4.6 Participants with suspicion or prior history of treated central nervous system (CNS) 
metastases with no evidence of active disease (assessed by MRI or contrast CT scan of 
the brain and spinal column) are eligible if pretreatment brain MRI demonstrate no 
evidence of disease in the past 4 weeks prior to entry.
2.1.1.4.7 Major surgical procedure, other than for diagnosis, must not occur within 4 weeks prior 
to the first dose of study treatment. Participants must have recovered adequately from 
the toxicity and/or complications from the intervention prior to starting the study drug.
2.1.1.4.8 Participants with prior cancer-directed therapy must have a washout period of 3 weeks 
prior to the first dose of study treatment.
2.1.1.4.9 Participants with prior cancer-directed immunotherapy-based therapy must have a 
washout period of 4 weeks prior to the first dose of study treatment.
2.1.1.4.10 Human immunodeficiency virus (HIV)-infected participants are eligible if on stable 
dose of highly active antiretroviral therapy (HAART), a CD4 count ≥ 200 cells/mcL, 
and an undetectable viral load (VL). 
2.1.1.4.11 Hepatitis B virus (HBV) positive participants are eligible if they have been treated or 
are on an appropriate course of antivirals at study entry. 
2.1.1.4.12 Participants with a history of hepatitis C virus (HCV) infection (i.e., positive HCV 
antibody test) must have been treated and cured (undetectable HCV VL at screening). 
Participants with HCV infection who are currently on treatment are eligible if they have 
an undetectable HCV VL. 
2.1.1.4.13 Individuals of child-bearing potential (IOCBP) must agree to use an effective method 
of contraception (barrier, surgical sterilization, abstinence) prior to study entry, for the 
duration of study participation, and for at least 6 months after the last dose of study drug.
2.1.1.4.14 IOCBP must undergo pregnancy testing at screening and must not be pregnant in order 
to take part. Note: In these cases, a negative β-human chorionic gonadotropin (β-hCG) 
(urine or blood) is required.
2.1.1.4.15 Nursing participants must discontinue nursing and/or not begin nursing until 1 month 
after the last dose of study drug.
2.1.1.4.16 Ability of participants to understand and the willingness to sign a written informed 
consent document.
2.1.2
Exclusion Criteria
2.1.2.1
Participants who are receiving any other investigational agents 
2.1.2.2
Primary platinum-refractory ovarian cancer (defined as progression while on the upfront 
platinum-based therapy)

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2.1.2.3
Participants with any other concomitant invasive malignancies
2.1.2.4
History of severe hypersensitivity or allergic reactions attributed to compounds of similar 
chemical or biologic composition to SG, SN-38, or irinotecan.
2.1.2.5
Prior treatment with TROP2-targeting ADC. Participants with prior use of other ADCs 
are eligible. 
2.1.2.6
Prior treatment with topoisomerase 1 inhibitors i.e., topotecan
2.1.2.7
Symptomatic or untreated brain/CNS metastases
2.1.2.8
Participants who require treatment with UGT1A1 inhibitors (see Section 4.1). 
2.1.2.9
Participants with known homozygous UGT1A1*28 allele if tested during the previous 
treatment. 
2.1.2.10 Participants with active infection requiring antibiotics.
2.1.2.11 Participants who have not recovered from toxicities or AEs related to prior therapy to 
Grade ≤ 1 with the following exceptions.  
•
Participants with platinum related hypomagnesemia (on replacement) are eligible.
•
Participants with auto-immune thyroid dysfunction on stable replacement therapy 
are eligible. 
•
Participants with any grade alopecia or grade 1 or 2 neuropathy are eligible.  
2.1.2.12 Participants with a history of gastrointestinal (GI) perforation or hemorrhage (> 30mL 
bleeding/episode) fistula or hemoptysis within 3 months prior to initiation of study 
therapy, intra-abdominal abscess in the 6 months prior to entry, history of ascites or 
pleural effusion requiring paracentesis or thoracentesis in the 4 weeks prior to initiation 
of study therapy or history of bowel obstruction within 3 months prior to initiation of 
study therapy. 
2.1.2.13 Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study 
treatment, or anticipation of need for such a vaccine during SG treatment or within 5 
months after the final dose of SG. Note: Seasonal flu vaccines that do not contain a live 
virus and locally authorized/approved COVID-19 vaccines are permitted (see also 
Section 4.1)
2.1.2.14 Participants with severe uncontrolled intercurrent illness that would limit compliance 
with study requirements, evaluated by history, physical exam, and chemistry panel.
2.2
RECRUITMENT STRATEGIES
All participants will be enrolled and generally expected to be recruited from, but not limited to, 
the United States.
The protocol may be abstracted into a plain language announcement-information to be abstracted 
includes-study title; purpose of the study; protocol summary; basic eligibility criteria; study site 
location(s); and how to contact the site for further information) and posted/distributed on the below 
media without IRB approval. Should we add additional descriptive information about the study to 
these announcements, we will seek IRB approval.
Recruitment strategies may include:

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1. The study may be publicized on 
a.
NIH official websites; (e.g., www.clinicaltrials.gov., NCI cancer clinical trial 
listing [PDQ], CCR)
b. NIH moderated social medical platforms (e.g., Facebook, X, Instagram. These 
sites comply with government terms of service per the NIH Social Media 
Guidelines)
c.
Research Match (https://www.researchmatch.org/about/)
2. Newsletters (if intent is to recruit)
3. Television advertisements/radio advertisements
a.
Clinical Center TV (CCTV) – Clinical Center Television - CCTV | NIH Clinical 
Center - America's Research Hospital TVs placed all around the NIH Clinical 
Center will rotate through various messages including one for this study.
4. Newspaper advertisements
5. Videos
6. Publicly posted recruitment flyers and posters
7. Brochures
8. Clinical Center Office of Patient Recruitment Services (OPR) including OPR Listservs 
(Email list of those interested in receiving study recruitment updates). Includes the OPR 
Protocols and OPR Healthy Volunteers listservs and 3 NIH listservs (NIH Post bac, 
NIH Clinical Fellows & NIH Study Volunteers) 
9. Recruitment Letters 
a.
Doctor to patient informational letter: distribution of letters to private health 
care physicians/providers- these professionals will share study information with 
potential participants. This information will be made available in electronic 
and/or a hard copy as needed. (Note: if material is not to be shared with 
participants, these are not submitted to the IRB)
b. Investigator to potential participant letters
Prior to distribution of any individual recruitment materials not excepted in item #1, such 
materials will be submitted for IRB review, as appropriate.
2.3
SCREENING EVALUATION
2.3.1
Screening activities performed prior to obtaining informed consent. 
Minimal risk activities that may be performed before the participant has signed a consent include 
the following: 
•
Email, written, in person or telephone communications with prospective participants 
•
Review of existing medical records to include H&P, laboratory studies, etc. 
•
Review of existing MRI, x-ray, or CT images
•
Review of existing photographs or videos

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•
Review of existing pathology specimens/reports from a specimen obtained for diagnostic 
purposes
2.3.2
Screening activities performed after a consent for screening has been signed
The following activities will be performed only after the participant has signed the consent for this 
study. Assessments performed at outside facilities or on other NIH protocols within the timeframes 
below may also be used to determine eligibility once a participant has signed the consent.
The following screening evaluations must be completed:
2.3.2.1
Performed within 10 years prior to treatment initiation
•
Confirmation of diagnosis: Obtain archival tumor specimen (one block of tissue or 20 
paraffin-embedded unstained slides) for all participants for confirmation of histology by 
the NCI Laboratory of Pathology (LP) or by an outside pathologist. Results from any 
US or Canadian certified labs may be acceptable for eligibility and treatment initiation. 
If archival tumor specimen is unavailable for confirmation of diagnosis, then samples 
from the fresh tumor biopsy will be used for confirmation of diagnosis by NCI LP.
•
Documentation of BRCA mutation (Cohort 1 only) by any US or Canadian certified 
lab 
2.3.2.2
Performed within 4 weeks prior to treatment initiation 
2.3.2.2.1 Radiographic studies
•
CT scan of chest, abdomen, and pelvis (CAP) with contrast. MRI abdomen/pelvis with 
gadolinium may be performed in participants unable to tolerate contrast for CT.
•
Brain MRI in participants with suspicion or prior history of treated CNS metastases
2.3.2.3
Performed within 3 weeks prior to treatment initiation
2.3.2.3.1 Clinical examination
•
Complete medical history and physical examination (including height, weight, vital 
signs)
•
ECOG performance status evaluation (see Appendix A: Performance Status 
Criteria)
•
Review of concomitant medications
•
Review of contraception
2.3.2.3.2 Clinical laboratory data
•
Complete blood count (CBC) with differential: includes Neutrophils, Lymphocytes, 
Monocytes, Eosinophils, Basophils, WBC, RBC, Hemoglobin, Hematocrit, MCV, 
RDW, Platelet
•
Serum Chemistries:
o
Acute care panel (sodium, potassium, chloride, total CO2, creatinine, glucose, 
urea nitrogen) 
o
Mineral panel (albumin, calcium total, magnesium total, phosphorus)

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o
Hepatic panel (alkaline phosphatase, ALT, AST, total bilirubin, direct bilirubin) 
•
PT/INR and aPTT (required for pretreatment biopsy)
•
HIV screening antibody, CD4 count and VL if positive
•
Hepatitis B surface antigen
•
Hepatitis C antibody panel with reflex VL
•
Pregnancy test (serum or urine β-hCG) in IOCBP* 
*IOCBP: Any person who is postmenarchal, has not reached a postmenopausal state 
(≥ 12 continuous months of amenorrhea with no identified cause other than 
menopause), and has not undergone surgical sterilization (removal of ovaries, 
fallopian tubes and/or uterus) or another cause as determined by the treating 
investigator (e.g., Müllerian agenesis). Per this definition, a person with a tubal 
ligation is considered to be of childbearing potential. The definition of childbearing 
potential may be adapted for alignment with local guidelines or requirements.
2.3.2.3.3 Other evaluations
•
12-lead electrocardiogram (EKG) to rule out cardiotoxicity from previous therapy
2.4
PARTICIPANT REGISTRATION AND STATUS UPDATE PROCEDURES
Registration and status updates (e.g., when a participant is taken off protocol therapy and when a 
participant is taken off-study) will take place per CCR SOP ADCR-2, CCR Participant 
Registration & Status Updates found at: https://nih.sharepoint.com/sites/NCI-CCR-OCD-
Communications/SitePages/OEC-Administrative---Clinical-Research-(ADCR).aspx?Mode=Edit.
2.4.1
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently assigned to the study intervention. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants, to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details, and 
eligibility criteria.
Individuals who do not meet the criteria for participation in this trial (screen failure) because of a 
transient underlying condition not related to the condition under study may be rescreened once 
after the underlying condition has resolved.
2.4.2
Treatment Assignment Procedures
Cohorts  
Number
Name
Description
1
Cohort 1
Participants with recurrent/metastatic ovarian carcinoma
2
Cohort 2
Participants with recurrent/metastatic endometrial carcinoma
3
Cohort 3
Participants with recurrent/metastatic cervical carcinoma

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Arms
Number
Name
Description
1
Arm 1
Treatment with SG 
Arm Assignment
Participants in Cohorts 1, 2, and 3 will be assigned to Arm 1.
3
STUDY IMPLEMENTATION
3.1
STUDY DESIGN
This is an open-label Phase II, single arm, pilot study to investigate the anti-tumor activity of SG 
in recurrent gynecologic cancers. 
Participants will receive SG at 10mg/kg by intravenous (IV) infusion on Days 1 and 8 of every 21-
day cycle in the outpatient setting. The standard dose adjustment algorithm defined in the SG 
package insert will be used to make decisions on dose reductions, interruptions or discontinuation 
of SG treatment based on adverse events that may occur during participants’ treatments. 
Restaging will be time-based and performed every 9 weeks (± 1 week, approximately every 3 
cycles) for the first year, and every 12 weeks (± 1 week, approximately every 4 cycles) thereafter 
until disease progression or up to 5 years.
SG will be administered for a maximum of 5 years, or until participants experience adverse events 
requiring treatment discontinuation (see Section 3.2.1), trial withdrawal, progression, or as 
determined by the Principal Investigator (PI) after an integrated assessment of radiographic and 
biochemical data, biopsy results (if available), and clinical status (e.g., symptomatic deterioration 
such as pain secondary to disease).  All study participants will be followed-up for 10 years after 
completion of therapy (see Section 3.3.1).
3.2
DRUG ADMINISTRATION
SG may be dispensed only under the supervision of the PI or an authorized designee and only for 
administration to the study participants. The FDA-approved product labeling for SG includes a 
boxed warning for neutropenia and withhold if ANC < 1500 on D1 or < 1000 on D8) on the day 
of scheduled treatment. 
SG is administered as an IV infusion on days 1 and 8 of a 21-day cycle. Dosing is based on the 
participant’s body weight on day 1 and day 8 of each cycle. If the participant’s body weight is 
within 10% of the previous cycle, the same dose may be carried forward based on local site 
procedures. 
Do not administer as an IV push or bolus. Do not administer other drugs concurrently with SG 
through the same intravenous line. 
SG has a known risk of infusion-related reactions. Therefore, for each participant, the first infusion 
will be run over 3 hours. If well-tolerated, subsequent infusions may be given over 1-2 hours. 
Participants will be monitored, including vital signs during each hour of the infusion and for at 
least 30 minutes following the completion of the infusion.

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SG should be administered in a setting that allows for immediate access to an intensive care unit 
and administration of therapy for anaphylaxis, such as the ability to implement immediate 
resuscitation measures. Steroids (dexamethasone 10 mg), intramuscular epinephrine (1:1,000 
dilution), allergy medications (IV antihistamines), bronchodilators, or equivalents, and oxygen 
should be available for immediate access.
To prevent or reduce the severity of infusion-related reactions, premedication with an antipyretic, 
an H1 and H2 blocker approximately 30 to 60 minutes prior to each dose of SG is mandatory for 
the first 2 infusions and is optional and at the discretion of the treating investigator after the second 
infusion.
If an allergic reaction occurs, the subject must be treated according to the best available medical 
practice. Please see the guidelines for anaphylaxis management in Appendix B: Anaphylaxis 
Precautions.
See Section 13.1.3 for drug preparation information.
3.2.1
Dose Modifications
Dose modification is allowed for infusion-related reactions. In these cases, SG infusion will be 
slowed or interrupted. For life-threatening infusion-related reactions, SG will be permanently 
discontinued. Other adverse events attributable to SG will be managed as per Table 2. 
Table 2 reflects additional appropriate dose reduction and/or medical management [97].
Table 2: Recommended Dose Modification Schedule for SG
Adverse Reaction
Occurrence
Dose Modification or Action
Severe neutropenia 
First
Reduce dose to 7.5 mg/kg 
and administer granulocyte 
– colony stimulating factor 
(G-CSF) as soon as 
clinically indicated
Second
Reduce dose to 5 mg/kg and 
administer G-CSF as soon 
as clinically indicated
Grade 4 neutropenia ≥ 7 days or less if clinically indicated,
OR
Grade 3 or Grade 4 febrile neutropenia, 
OR
At time of scheduled treatment, Grade 3 or Grade 4 
neutropenia that delays dosing by up to 3 weeks for 
recovery to ≤ Grade 1
Third
Discontinue treatment and 
administer G-CSF as soon 
as clinically indicated
At time of scheduled treatment, Grade 3 or Grade 4 
neutropenia that delays dosing beyond 3 weeks for 
recovery to ≤ Grade 1
First
Discontinue treatment and 
administer G-CSF as soon 
as clinically indicated
Severe nonneutropenic toxicity
Grade 4 nonhematologic toxicity of any duration,
OR
First
Reduce dose to 7.5 mg/kg

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Adverse Reaction
Occurrence
Dose Modification or Action
Second
Reduce dose to 5 mg/kg
Any Grade 3 or Grade 4 nausea, vomiting, or diarrhea due 
to treatment that is not controlled with antiemetics and 
antidiarrheal agents 
OR
At time of scheduled treatment, Grade 3 or Grade 4 
nonneutropenic hematologic or nonhematologic toxicity 
that delays dose by 2 or 3 weeks for recovery to ≤ Grade 1
Third
Discontinue treatment
In the event of Grade 3 or Grade 4 nonneutropenic 
hematologic or nonhematologic toxicity, Grade 3 nausea, 
or Grade 3-4 vomiting that does not recover to ≤ Grade 1 
within 3 weeks 
First
Discontinue treatment
Infusion-related toxicities
Grade 2 or Grade 3 infusion-related reaction despite 
optimal management
Recurrent
Discontinue treatment
Grade 4 infusion-related reaction
First
Discontinue treatment
3.2.1.1
Adverse Event Management
3.2.1.1.1 Gastrointestinal toxicities
Nausea, vomiting, and diarrhea are frequent toxicities associated with SG. Appropriate monitoring 
and treatment, including fluid and electrolyte replacement as clinically indicated, is required to 
minimize the risk of serious consequences such as dehydration. Instructions for SG dose 
modification for treatment-related toxicities are provided in Table 2.
3.2.1.1.1.1 Nausea and Vomiting
For prevention of chemotherapy-induced nausea and vomiting, a 2- or 3-drug combination regimen 
(e.g., dexamethasone with either a 5-HT3 receptor antagonist or a neurokinin 1 (NK1) receptor 
antagonist, as well as other drugs, as indicated) should be used as premedication. 
Additional antiemetics and other supportive measures may also be employed as clinically 
indicated. All participants should be provided with a prescription with clear instructions for 
antiemetics to take at home for prevention and treatment of nausea and vomiting.
3.2.1.1.1.2 Diarrhea
At the onset of diarrhea, an evaluation for infectious causes should be performed and, if negative, 
loperamide should be promptly initiated at 4 mg initially followed by 2 mg with every episode of 
diarrhea for a maximum of 16 mg daily. Loperamide should be discontinued 12 hours after the 
diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may 
also be employed as clinically indicated.
Participants who exhibit an excessive cholinergic response to treatment with SG (e.g., abdominal 
cramping, diarrhea, salivation) can receive appropriate premedication (e.g., atropine) for 
subsequent treatments.
If a participants develop diarrhea, anti-diarrheal agents and hydration will be initiated. 

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•
The recommended treatment includes loperamide (Imodium) and 20 mg of 
diphenoxylate/atropine (Lomotil) administered according to package insert guidelines. If 
grade 2 diarrhea is seen in 2 subjects early in the trial, prophylactic antidiarrheals will be 
administered for all subsequent doses and cohorts. 
•
In case of diarrhea while on prophylactic loperamide, continue loperamide and start 
immediately two Lomotil tablets four times daily or 10 ml (two regular teaspoonfuls) of 
Lomotil liquid four times daily (20 mg per day). Most participants will require this dosage 
until initial control has been achieved, after which the dosage may be reduced to meet 
individual requirements. 
•
If no improvement in 48 hours after starting Lomotil, add Tincture (50 mg/5 mL) 6 mg (0.6 
mL) by mouth (PO) every 6hr; not to exceed 6 mL/day. Prophylactic or therapeutic 
treatment with atropine in participants experiencing early onset diarrhea with cholinergic 
symptoms (0.25 mg to 1 mg, administered intravenously or subcutaneously), should be 
considered unless contraindicated.
3.2.1.1.2 Anemia
Anemia is a known adverse effect attributed to SG. 
For anemia events assessed as treatment-related, items queried may include, but are not limited to, 
detailed relevant past medical and treatment history, bruising tendency, history of blood 
transfusions and/or dependency, and a request for an updated electronic Case Report Form (eCRF) 
including details such as concomitant medications, all laboratory data, updated dosing information 
and recent tumor evaluation scans.
A thorough investigation of new anemia cases of unspecified etiology is requested. Safety 
laboratory testing of relevant blood parameters is conducted per schedule of assessment.
General Guidance for anemia management and evaluation:
•
Participants must enter the study with Hgb values at least 9 g/dL 
•
All relevant hematologic testing for treatment related anemias should be done prior to 
blood transfusion, if clinically feasible.
•
Transfusion should be performed at the discretion of the treating investigator, based on 
clinical assessment and considered when participant experiences significant anemia. 
Guidance for evaluation of suspected treatment-related anemias is provided in Table 3.

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Table 3: Diagnostic workup for anemia
Baseline anemia evaluation (prior to transfusion, if feasible)
CBC with differential (i.e., hemoglobin, hematocrit, MCV, RDW, WBC/ANC) and 
reticulocyte count
Evaluation of CBC post-transfusion for adequacy of increase in 
hemoglobin/hematocrit
Evaluation of CBC post iron repletion (PO or IV) for increase in 
hemoglobin/hematocrit, reticulocyte count, and RDW
Complete metabolic panel, including liver function panel (AST/ALT, bilirubin), LDH, renal 
function, and serum folate/B12
Coagulation indices (PT, PTT, INR)
Urinalysis and urine culture 
Iron panel (iron, TIBC, ferritin, transferrin saturation)
TSH
Fecal-occult blood testing
Haptoglobin
Further recommendation based on suspected etiology (in addition to baseline anemia testing)
Unknown etiology, 
suspect hemolysis
Coombs test, fibrinogen, d-dimer, LDH
Peripheral blood smear for cell morphological assessment
Consider hematology consultation
Unknown etiology, 
suspect possible 
bleeding
Consider blood transfusion at clinical discretion.
Consider gastroenterology consultation/ endoscopy (upper/lower)
Consider surgical/interventional radiology (IR) consultation.
Consider advanced imaging, as clinically indicated (e.g., FAST scan, CT 
scan, MRI, angiography).
Unknown etiology 
despite above work-
up (including 
suspected aplastic 
anemia
Hematology consultation
Consider bone marrow aspiration/morphologic evaluation
Management Options
Packed red blood cell (PRBC) transfusion
Iron repletion (in case of iron deficiency, as revealed above) – PO or IV iron repletion
Erythroid growth factor support (i.e., erythropoietin)
Addressing source of blood loss (endoscopy, vessel embolization by Interventional radiology 
(IR)
Consideration for discontinuation of study medication
3.2.1.1.3 Participants with reduced UGT1A1 activity
Participants homozygous for the UGT1A1*28 allele are potentially at increased risk for adverse 
reactions, including neutropenia, febrile neutropenia, and anemia and are excluded from entry into 
this trial, but participants heterozygous UGT1A1*28 allele are still at higher risk for grade 3 to 4 
neutropenia, grade 3 to 4 febrile neutropenia and grade 3 to 4 anemia compared to patients 
homozygous for wild type allele as shown below in Table 4. These AEs will be managed as per 
Table 2.

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Table 4:  Incidence of Adverse Reactions in Patients with Reduced UGT1A1 Activity
Adverse event
Homozygous for 
UGT1A1*28 Allele 
(N = 112)
N (%)
Heterozygous for 
UGT1A1*28 Allele 
(N = 420)
N (%)
Homozygous for Wild-
type Allele 
(N = 416)
N (%)
Grade 3 to 4 
neutropenia
65 (58%)
204 (49%)
180 (43%)
Grade 3 to 4 febrile 
neutropenia
16 (14%)
22 (5%)
23 (6%)
Grade 3 to 4 anemia
24 (21%)
41 (10%)
39 (9%)
3.3
ON STUDY ASSESSMENTS/EVALUATIONS
3.3.1
Timing of Procedures
The following describes all tests and procedures to be conducted during treatment. 
Refer to Study Calendar (Section 3.4) for timing and applicable windows. 
For each time period, consider the following order of assessments:
•
Screening: Refer to Section 2.3. 
•
Baseline/Cycle 1 Day 1: The results of all assessments must be available and reviewed 
prior to initiation of the study drug administration to ensure results still meet standards 
defined in eligibility criteria. All subjects are required to complete baseline evaluations per 
the Study Calendar (Section 3.4) within 10 days prior to the first planned dosing of the 
study drugs, except for imaging tests that are required to be done within 14 (+3) days prior 
to treatment initiation. Any screening tests performed within the specified time frame for 
baseline do not need to be repeated. 
•
Subsequent Cycles: 
o
Each cycle is 21 days. Beginning with Cycle 2, a permitted range of ±7 days due to 
scheduling or logistical reasons is permitted; however, day 1 of SG in a new cycle 
may be dosed no less than 14 days from the previous dose of SG (Day 8; [i.e., the 
Day 8 infusion will be counted as the first day of that 14-day period]). The Day 8 
dose of SG may be given no earlier than 6 days from the Day 1 dose (-1/+2 days). 
The scheduled Day 1 and Day 8 infusions may be delayed for up to 3 weeks for 
treatment-related toxicities.
o
Pre-Day 1 of each cycle assessment may be done up to 4 days (-4) prior to the start 
of the cycle.
o
The results of all assessments must be available and reviewed prior to initiation of 
study drug administration in a new cycle to confirm safety and eligibility for 
ongoing treatment administration. Components of these panels that are specifically 
relevant to monitoring the effects of the study drug are specified in “Laboratory 
Assessment” later in this section. The remaining laboratory values collected on 
these panels are part of standard of care assessments and unrelated to research. The 
cycle should be delayed if these criteria are not met (refer to Dose Modifications, 
Section 3.2.1).

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•
Study Drug Administration: 
o
SG will be administered IV on D1 and D8 of 21-day cycles. 
o
Treatment will be outpatient and will be given until unacceptable toxicity, trial 
withdrawal, progression/loss of clinical benefit as determined by the treating 
investigator (refer to Section 3.6.1), or up to a maximum of 5 years.
•
Unscheduled Visits: In the event of an unscheduled/unplanned visit (e.g., additional 
clinical assessment(s) due to toxicity), the treating investigator should use best clinical 
judgement as to the necessary assessments. In the event that the decision is made to 
continue treatment, all tests/assessments as required by the next visit on the Study Calendar 
(Section 3.4) should still be conducted (or repeated) within the applicable windows. If a 
decision is made to discontinue treatment, the participant should move to the End of 
Treatment (EoT) visit, with tests/assessments completed (or repeated) within the applicable 
windows. 
•
End of Treatment Assessments: The EoT visit will be performed up to 14 days after the 
participant comes off treatment (see Section 3.6.1) or before the initiation of a new anti-
cancer treatment, whichever comes first. 
•
30-day Safety Visit: The mandatory Safety Follow-up (FU) visit should be conducted 
approximately 30 (+ 14) days after the last dose of study drug or before initiation of a new 
anti-cancer treatment, whichever comes first (see assessments, Section 3.4). In addition, 
the study team will confirm contact information for participant and a designated family 
member and remind participant of follow-up contact that will be conducted for survival 
status. If the participant cannot return to the study center for this visit, the participant may 
complete assessments locally, including seeing a local physician for a physical exam and 
local clinical laboratories, and the study team will follow-up with the participant remotely.
•
Long-term Follow-up: Overall survival will be collected for 10 years for all study 
participants. Participants will be contacted remotely (e.g., phone or email) approximately 
every 6 months (± 30 days) after the safety visit.
•
Additional Information: If a physical exam and vital signs are required by the study 
calendar for participants on study therapy, then an in-person clinic visit is required. 
However, if participants are unable to travel to the study site for assessment during the 
specified window due to extenuating circumstances such as illness, travel restrictions, 
inclement weather, etc., every effort should be made for the participant to complete the 
required evaluation with their local medical provider. For safety visit, a telehealth visit may 
be conducted so that participants need not travel to the study site for evaluation unless 
preferred by the participant or felt to be clinically indicated by the provider. In these 
instances, participants will be contacted by phone, email or other institutional approved 
remote platform used in compliance with local policy (e.g., including HRPP Policy 303 for 
NIH participants).

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3.3.2
Description of Procedures
The following is a description of all procedures:
•
Symptom assessment: verbal review of participant’s current symptoms to establish a 
baseline.
•
Physical exam, including height, and weight: review of organ systems, weight (kg), height 
(at screening only)to determine eligibility and establish a baseline.
•
Vital signs (i.e., temperature, blood pressure, heart rate and respiratory rate) performed at 
screening to determine eligibility and establish a baseline, and before, during and after each 
SG administration to monitor safety.
•
Documentation of BRCA mutation (Cohort 1 only) from any certified lab to assess 
eligibility
•
Documentation of and MMR status (Cohort 2 only) and HPV infection status (Cohort 3 
only) from any certified lab to establish a baseline.
•
Performance status (ECOG): an assessment of activities of daily living; see Appendix A: 
Performance Status Criteria to assess eligibility, and to assess response to therapy at 
subsequent timepoints.
•
Laboratory assessments: the following comprises the required tests/analytes to assess 
eligibility at the time of screening, determination of baseline and treatment continuation 
per Section 3.2.1, and/or the safety of the study drug at subsequent timepoints unless 
otherwise noted. Additional laboratories may be ordered as part of panels (e.g., acute care 
panel, comprehensive chemistry, etc.). Given that the methodologies utilized are similar 
across all laboratories, no significant variability is expected and there is no anticipation that 
study data will be affected.
o
CBC with differential 
o
Serum Chemistries: 
➢Acute care panel includes Sodium (Na), Potassium (K), Chloride (Cl) Total 
CO2 (Bicarbonate), Creatinine, Glucose, Urea nitrogen 
➢Hepatic panel includes alkaline phosphatase (AP), ALT, AST, Total 
Bilirubin, Direct Bilirubin 
➢Mineral panel includes Albumin, Calcium, Magnesium, Phosphorus 
o
PT/INR and aPTT
o
CA125 (Cohorts 1 and 2 only) 
o
Ionized calcium, amylase, lipase 
o
Lactate dehydrogenase (LDH)
o
Viral screen:  HBsAg, HIV and HCV antibody, 
o
CD4 count and HIV VL if HIV positive; HCV viral load if HCV antibody positive
o
HPV DNA testing (Cohort 3 cervical cancer patients only)

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o
Urinalysis
o
Pregnancy test (serum or urine β-hCG) in IOCBP
•
Other evaluations:
o
Electrocardiogram (EKG) to determine eligibility
•
Imaging scans: 
o
Brain MRI – performed to assess eligibility
o
CT CAP scans with intravenous contrast. If a CT scan with intravenous contrast is 
contraindicated (e.g., in participants with impaired renal clearance), a non-contrast 
CT scan of the chest and MRI scans of the abdomen and pelvis should be 
performed. 
Imaging will be performed every 9 weeks (3 cycles) ± 7 days for the first year and 
every 12 weeks (4 cycles) ± 7 days thereafter until disease progression. 
•
Review of concomitant medications: Concomitant medications will be collected 
throughout the study until 30 days after the last dose of the study drug or start of new 
anticancer treatment, whichever comes first (also see Section 6.1).
•
Contraception review: Review of contraception use for IOCBP to assess eligibility and to 
determine continuation of treatment per Sections 2.1.1.4.13.
•
Correlative research samples: Refer to Section 5.

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3.4
STUDY CALENDAR
Cycle = 21 days
Procedure
Screening
Baseline/
C1D1
C1D8
Subsequent Cycles D1 Subsequent 
Cycles D8 
End of 
Treatment 
Assessments
30-day 
Safety 
Visit
Long-term 
Follow-up
≤3 weeks
≤10 days
-1/
+2 days
-4 days
+14 days
+14 days
every 6 months 
±30 days for
10 years
Window(s):
Section 2.3.2
Section 3.3.1
Confirmation of pathology/biopsy
X1
Medical history
X
Symptom assessment/Adverse events
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
X
Vital Signs
X
X5
X5
X5
X5
X
Weight
X
X
X
X
X
Height
X
Performance status (ECOG)
X
X
X
X
X
X
X
Documentation of BRCA mutation 
(Cohort 1 only)
X1
Documentation of MMR status (Cohort 
2 only) and HPV infection status 
(Cohort 3 only)
X1
Concomitant medications
X
X
X
X
X
X
X
Review contraception
X
X
Permitted as remote visits
X
Ongoing survival assessment by phone, 
email, or other remote platform
X
Clinical Laboratories
CBC with differential
X
X
X
X
X
X
Acute care, mineral, and hepatic 
panels 
X
X
X
X
X
PT/INR and aPTT
X

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Cycle = 21 days
Procedure
Screening
Baseline/
C1D1
C1D8
Subsequent Cycles D1 Subsequent 
Cycles D8 
End of 
Treatment 
Assessments
30-day 
Safety 
Visit
Long-term 
Follow-up
≤3 weeks
≤10 days
-1/
+2 days
-4 days
+14 days
+14 days
every 6 months 
±30 days for
10 years
Window(s):
Section 2.3.2
Section 3.3.1
CA125
X6
Ionized calcium, amylase, lipase
X
LDH
X
HIV, CD4 count, and reflex VL
X
HBV
X
HCV with reflex VL
X
HPV DNA (Cohort 3 only)
X
Urinalysis
X
Pregnancy Test (serum or urine β-
hCG)
X
X
X
Radiology/ Other Assessments
EKG
X
CT scans
X2
X
within 14 
(+3) days
X 
from C3 every 3 cycles 
±7 days for the first 
year and then every 4 
cycles ±7 days until PD 
or up to 5 years
X
Brain MRI 3
X2
X
within 14 
(+3) days
Study Drugs
SG
X
X
X
X
Correlative Studies
Blood (5.1.2)
X
X4
X
(C3 only)
X

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Cycle = 21 days
Procedure
Screening
Baseline/
C1D1
C1D8
Subsequent Cycles D1 Subsequent 
Cycles D8 
End of 
Treatment 
Assessments
30-day 
Safety 
Visit
Long-term 
Follow-up
≤3 weeks
≤10 days
-1/
+2 days
-4 days
+14 days
+14 days
every 6 months 
±30 days for
10 years
Window(s):
Section 2.3.2
Section 3.3.1
Tumor biopsy (5.1.3)
X
X 
(optional)
1.
Performed within 10 years prior to treatment initiation
2.
Performed within 4 weeks prior to treatment initiation
3.
In participants with suspicion or prior history of treated CNS metastases only
4.
Approximately 24-48 hours after the second dose of treatment
5.
SG administration vital signs will include temperature, blood pressure, heart rate, and respiratory rate within 30 minutes prior to infusion, every 60 
minutes during the infusion (±10 minutes), at end of infusion (±10 minutes), and 30 minutes post-infusion (±10 minutes)
6.
For Cohorts 1 and 2 only.

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3.5
COST AND COMPENSATION 
3.5.1
Costs
NIH does not bill health insurance companies or participants for any research or related clinical 
care that participants receive at the NIH Clinical Center. If some tests and procedures are 
performed outside the NIH Clinical Center, participants may have to pay for these costs. 
3.5.2
Compensation
Participants will not be compensated on this study. 
3.5.3
Reimbursement 
The NCI will cover the costs of some expenses associated with protocol participation. Some of 
these costs may be paid directly by the NIH and some may be reimbursed to the 
participant/guardian as appropriate. The amount and form of these payments are determined by 
the NCI Travel and Lodging Reimbursement Policy.
3.6
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA
Prior to removal from study, effort must be made to have all subjects complete a safety visit 
approximately 30 days after the last dose of study medication. 
3.6.1
Criteria for removal from protocol therapy
•
Completion of study therapy
•
Progressive disease (see Section 6.3)
•
Participant request/voluntary withdrawal from the study therapy
•
Adverse events that require treatment discontinuation as explained in Section  3.2.1
•
Intercurrent illness that prevents further administration of treatment 
•
The treating investigator determines further treatment on this study is not in participant’s 
best interest
•
Pregnancy 
•
Requirement for use of prohibited therapies as listed in Section 4.1
3.6.2
Off-Study Criteria
•
Screen failure or failure to maintain eligibility prior to initiation of treatment
•
Completion of 10-year follow-up period
•
Study is stopped for any reason
•
Participant request to be withdrawn from study
•
Non-compliance with study treatment and/or testing
•
Lost to follow-up. 
•
Death

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3.6.3
Lost to Follow-up
A participant will be considered lost to follow-up if he or she fails to return for 3 scheduled clinic 
visits and is unable to be contacted by the study site staff. 
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit:
•
The site will attempt to contact the participant and reschedule the missed visit for 2 months 
and counsel the participant on the importance of maintaining the assigned visit schedule 
and ascertain if the participant wishes to and/or should continue in the study.
•
Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, an IRB-approved certified letter to the participant’s last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
participant’s medical record or study file. 
•
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.
4
CONCOMITANT MEDICATIONS/MEASURES
Concomitant therapy consists of any medication (e.g., prescription drugs, over the counter drugs, 
vaccines, herbal or homeopathic remedies, nutritional supplements) used by a participant in 
addition to protocol-mandated treatment from 7 days prior to initiation of study treatment to the 
treatment discontinuation visit. All such medications should be reported to the treating investigator 
and recorded in the participant’s medical records.
4.1
PROHIBITED MEDICATION 
•
Drugs that inhibit UGT1A1 should not be administered while on study treatment. 
UGT1A1 inhibitors include indinavir, atazanavir, nilotinib, and sorafenib (as well as 
certain herbal extracts). UGT1A1 inducers should also be avoided. Additional guidance 
can be found in the following link: https://www.fda.gov/drugs/drug-interactions-
labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-
inducers#table3-2.
•
Concomitant therapy intended for the treatment of cancer (including, but not limited to, 
chemotherapy, immunotherapy, radiotherapy, and herbal therapy), whether health 
authority−approved or experimental, is prohibited for various time periods prior to 
starting study treatment, depending on the agent (see Section 2.1.1), and during study 
treatment, until disease progression is documented and the participant has discontinued 
study treatment with the exception of palliative radiotherapy and local therapy.
•
Any live attenuated vaccine therapies (e.g., FluMist®) for the prevention of infectious 
disease in the 4 weeks prior to initiation of study treatment, during and for 5 months 
following study treatment. Administration of inactivated vaccines (e.g., inactivated 
influenza vaccines), mRNA-based vaccines (e.g., Pfizer/BioNTech or Moderna vaccines 
against SARS-CoV-2) and monoclonal antibody treatment for acute treatment of SARS-
CoV-2 is allowed per local regulatory guidelines.

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•
If the administration of a non-permitted concomitant drug becomes necessary during the 
trial, the subject will be withdrawn from trial treatment.
4.2
PERMITTED MEDICINES/INTERVENTIONS
Any medications (other than those excluded by the clinical trial protocol) that are considered 
necessary to protect subject welfare and will not interfere with trial medication may be given at 
the treating investigator/designee’s discretion.
In case of surgery, SG should be interrupted for one week prior to surgery, if possible, and 2 weeks 
after the surgical procedure; restarting may be delayed for 4 weeks for major surgery (e.g., 
abdominal surgery, cranial surgery). Participants should be clinically stable prior to restarting 
treatment.
Participants are permitted to use the following therapies during the study:
•
Prophylactic or therapeutic anticoagulation therapy (such as warfarin at a stable dose or 
low-molecular-weight heparin)
•
Vaccinations (such as. influenza, SARS-CoV-2)
o
Live, attenuated vaccines are not permitted (see Section 4.2).
•
Megestrol acetate administered as an appetite stimulant 
•
Mineralocorticoids (e.g., fludrocortisone)
•
Corticosteroids administered for COPD or asthma
•
Low-dose corticosteroids administered for orthostatic hypotension or adrenocortical 
insufficiency
4.2.1
Prevention of Infusion-Related Reactions
•
Corticosteroids are permitted prior to the administration of SG for the prevention of 
infusion-related reactions or as part of an antiemetic regimen.
•
Premedication with antipyretics and H1 and H2 blockers prior to the start of the SG 
infusion. 
In general, the treating investigator should manage a participant’s care (including preexisting 
conditions) with supportive therapies other than those defined as cautionary or prohibited therapies 
(see Section 4.2) as clinically indicated, per local standard practice. Participants who experience 
infusion-associated symptoms may be treated symptomatically with acetaminophen, ibuprofen, 
diphenhydramine, and/or H2receptor antagonists (e.g., famotidine, cimetidine), or equivalent 
medications per local standard practice. Serious infusion-associated events manifested by dyspnea, 
hypotension, wheezing, bronchospasm, tachycardia, reduced oxygen saturation, or respiratory 
distress should be managed with supportive therapies as clinically indicated.
4.2.2
Growth Factor Support
Febrile neutropenia may occur with SG. Growth factors (i.e., G-CSF) will be recommended for 
the therapeutic management of neutropenia and as clinically indicated. For participants with 
homozygous UGT1A1*28 alleles (or other allows associated with reduced UGT1A1 expression 

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and/or enzymatic activity) or with high risks as per ASCO guidelines, G-CSF support may be used 
as primary prophylaxis. 
4.2.3
Transfusion Support
In prior clinical trials with SG, anemia occurred in 71% of participants (18% with Grade 3-4 
anemia), and thrombocytopenia occurred in 25% of participants (2% with Grade 3-4 
thrombocytopenia). Packed red blood cell (PRBC) transfusion will be allowed for the therapeutic 
management of symptomatic anemia and/or hemoglobin level below 9g/dL, as well as 
management of acute bleeding episodes. Diagnostic workup of anemia is detailed in Section 
3.2.1.1.2. In case of iron deficiency anemia, repletion with oral iron repletion is permitted. 
Intravenous iron repletion is also permitted if there is a contraindication to oral repletion or actual 
or anticipated intolerance to iron repletion. Platelet transfusion will be allowed for bleeding 
prophylaxis. 
4.2.4
Antiemetic Support
SG is considered to be moderately emetogenic; in TROPHY-U-01 (IMMU-132-06), 64% of 
participants receiving SG monotherapy experienced nausea (all grades) and 35% of participants 
experienced vomiting (all grades). Premedicate with a two or three drug combination antiemetic 
regimen according to institutional practice standards and/or national guidelines. Intravenous fluids 
(IV fluids)/electrolyte repletion may be administered to support rehydration at the discretion of the 
treating investigator. See Section 3.2.1.1.1.1 / Table 2 regarding dose modifications in the setting 
of persistent nausea/vomiting.
4.2.5
Antidiarrheal Support
SG monotherapy in TROPHY-U-01 (IMMU-132-06), 64% of participants experienced diarrhea 
(all grades), with 11% experiencing Grade 3 diarrhea. Subjects who exhibit acute onset diarrhea 
(within 24 hours of treatment) and/or an excessive cholinergic response to treatment with SG (e.g., 
abdominal cramping, diarrhea, salivation, etc.) can receive subcutaneous atropine or other 
appropriate medication for subsequent treatments. Infectious causes of the diarrhea will be 
evaluated and if negative, loperamide will be administered at the onset of treatment-related Grade 
1 or Grade 2 diarrhea, at an initial dose of 4 mg, followed by 2 mg with every episode of diarrhea 
to a maximum dose of 16 mg/day. If diarrhea is not resolved after 24 hours, consider adding 
diphenoxylate/atropine. Consider adding octreotide 100-150 mcg subcutaneous (SC) three times 
per day if diarrhea persists. IV fluids/electrolyte repletion may be administered to support 
rehydration at the discretion of the treating investigator. 
See Section 3.2.1.1.1.2 / Table 2 regarding dose modifications in the setting of persistent diarrhea 
potentially attributable to SG.

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5
CORRELATIVE STUDIES FOR RESEARCH 
5.1
BIOSPECIMEN COLLECTION
5.1.1
Sample Collection Table
Test/assay
Type of tubea 
and volume
Collection point 
Location of 
specimen 
analysisb
Blood Samples
Circulating tumor DNA 
(ctDNA)
2x10mL
Streck Tube
C1D1(prior to treatment), C1D8 & 
C3D1 (within 48 hours after the SG 
dose), EOT/at progression
Biospecimen 
Processing 
Core (BPC)
Circulating tumor cells (CTC)
1x10 mL
Streck Tube
C1D1(prior to treatment), C1D8 & 
C3D1 (within 48 hours after the SG 
dose), EOT/at progression
γH2AX expression
2x8 mL
CPT blue/black 
tube
C1D1(prior to treatment), C1D8 & 
C3D1 (within 48 hours after the SG 
dose), EOT/at progression 
DTB Clinical 
Translational 
Unit
UGT1A1 genotyping
1x6 mL
Lavender-top 
tube (K2EDTA) 
C1D1 (prior to treatment)
BPC
Tumor Samples
TROP2 IHC
FFPE ,
1 core
BPC/LP
Evaluation of DNA damage 
repair and other pathway 
genes (Next gene sequencing, 
whole genome sequencing 
and RNAseq)
FFPE/fresh 
frozen tissues, 
3 cores
Archival FFPE tissue if available, 
C1D1 (prior to treatment, mandatory 
except as noted in Section 5.1.3), 
EOT/at progression (optional)c
BPC/fee-for-
service Core 
lab 
TSO500
Archival, 10 
unstained slides 
or tissue block  
Archival FFPE tissues, C1D1 (prior 
to treatment)  
LP
a.
Please note that tubes and media may be substituted based on availability with the permission of the PI or 
laboratory investigator.
b.
The location of specimen analysis may be adjusted at the time the analyses are performed
c.
Biopsies may be not performed on the specific dates and times due to the following reasons, including but not 
limited to, delayed recovery of hematologic toxicities, delayed clinic schedule, or national holidays
5.1.2
Blood samples
Blood samples will be collected and processed according to validated standard operating 
procedures (SOPs) to maintain sample quality and participant confidentiality. All biospecimens 
will be collected during visits to NIH. 
5.1.3
Tumor tissues
Baseline research tumor biopsies are mandatory for every subject who is deemed safely able to be 
biopsied by Interventional Radiologist review. Biopsies at progression are optional. If a biopsy is 

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done for clinical reasons, samples will also be collected for research at that time, if feasible. No 
more than 2 biopsies per subject will be done for research during the study. 
Research biopsies will be performed under local anesthesia. General anesthesia may be provided 
as clinically indicated. 
Pretreatment tumor biopsies will be obtained by minimally invasive methods such as CT guided 
percutaneous biopsies. The biopsy site will be determined by a discussion between an 
interventional radiologist and the study PI or AI. 
Attempts will be made to obtain up to five cores if safe and feasible, which will be frozen for 
research studies. These tumor core biopsies will be obtained percutaneously or per vagina through 
interventional radiology as long as considered minimal surgical risk. Two 3-millimeter punch 
biopsies of skin will be acceptable in lieu of 18-gauge core biopsies for participants with skin 
involvement. Inability to get tissue with a reasonable attempt will not preclude treatment and the 
participant will remain eligible for all other translational components.
The use of imaging to facilitate biopsies will be decided upon by members of the interventional 
radiology team. Should CT scans be needed for biopsy, a limit of 2 scans for each procedure will 
be observed to minimize radiation exposure to the participant.
The schedule for the biopsies will be made with Special Procedures (e.g., Dr. Brad Wood). 
Members of the Biospecimen Procession Core (BPC) will be on call to receive and embed biopsies. 
•
One core biopsy will be sent to the LP to confirm the diagnosis and for TROP2 
immunohistochemical staining (see Section 5.2.2.1) 
•
The remaining core biopsies from pretreatment biopsy are to be immediately embedded, 
frozen, and stored, barcoded, in the BPC at -80oC until use. At least one tissue core will be 
paraffin-embedded, barcoded, and stored in the BPC until use. 
Any required consent for optional biopsies will be documented via procedure consents presented 
to the participants at the time of the procedure.
5.2
PLANNED ANALYSES
Note: Platforms and procedures may be adjusted based upon current technology and/or 
collaborations in place at the time of actual analyses.
5.2.1
UGT1A1 Genotyping 
Results from prior SG studies indicate that the frequency of some exposure related adverse events 
(i.e., anemia, neutropenia and febrile neutropenia) may be higher in subjects homozygous for the 
UGT1A1*28 allele; however, the frequencies of neutrophil count decreased and other treatment-
related adverse events, notably diarrhea, did not differ among the subgroups. 
UGT1A1*28 allele status will be evaluated as a possible marker of toxicity. Blood sample will be 
collected to analyze the genomic DNA and assess genotype of the most relevant drug metabolizing 
enzymes and transporters. DNA will be analyzed on a PharmacoScanTM (ThermoFisher) 
genotyping platform that tests for 4,527 genetic variations in 1,191 drug disposition genes, 
including CYP (phase I metabolism) genes, non-CYP (phase I metabolism) genes, phase II 
metabolizing genes (including UGTs), transporters, genes involved in facilitation of drug 
transporters, genes involved in global regulation of drug metabolizing/transporting proteins, drug 
binding proteins, and drug targets.

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The genes encoding the drug metabolizing enzyme UGT1A1 will be evaluated. Since 
PharmacoScan does not test the (TA)8 repeat in rs3064744, a fragment analysis assay to test 
UGT1A1 genotype was developed by the Clinical Pharmacology Program (CPP) [98]. This assay 
will be used by CPP to test this allele.
5.2.1.1
Analysis of circulating tumor cells (CTC)  
CTCs will be assessed using ferrofluidic enrichment and multiparameter flow cytometric detection. 
CTCs will be identified as viable, nucleated cells, that positively express one or more epithelial or 
tumor markers and are negative for expression of hematopoietic markers. CTCs will be further 
characterized for marker expression, including TROP2.
5.2.1.2
γH2AX-staining 
Peripheral blood mononuclear cells (PBMCs) will be assessed for γH2AX expression using 
multiparameter flow cytometry along with other markers.
5.2.2
Tumor studies
5.2.2.1
TROP2 IHC
TROP2 expression will be assessed by IHC to evaluate concordance (or discordance) between 
archival tumor tissues and fresh pretreatment biopsy samples. TROP2 IHC will be performed in 
one representative FFPE tumor section and evaluated independently by two pathologists at 
CCR/Laboratory of Pathology (LP). 
In previous studies, membranous expression is clinically relevant in breast and gynecologic 
cancers for prognosis and the use of ADC [77, 79, 91, 99, 100]. Therefore, TROP2 expression will 
be evaluated for membranous expression. Appropriate negative and positive controls will be 
performed with each case. Protein expression will be quantified using H-score calculated as 
follows: (1 × percentage of weak staining) + (2 × percentage of moderate staining) + (3 × 
percentage of strong staining) within the target region, ranging from 0 to 300 [79, 91, 99]. The 
final immunoreactivity score will be then classified into four ordinal categories: H score 0–9, 10–
99, 100–199, and 200–300 groups [79, 91, 99]. For the case where the H scores by two pathologists 
fall in different H-score groups, the two pathologists review the case together and get a consensus.  
Please email to Dr. Sun A. Kim, MD PhD at suna.kim@nih.gov as soon as the participant is 
scheduled for biopsy. 
5.2.2.2
DNA damage repair pathways
mRNA levels of key molecules of DNA damage response pathways (i.e., ATM, ATR, CCNE1 or 
RPA1) and/or specific mutations of genes will be assessed via Next gene sequencing/ whole 
genome sequencing/RNAseq along with γH2AX levels. This will be performed in an exploratory 
fashion. Results gleaned from the preliminary laboratory data in PI’s lab and findings from the 
latest literature may modify the other endpoints of DNA damage response pathways. 
5.2.3
Genomic studies
5.2.3.1
Circulating tumor DNA (ctDNA) 
ctDNA can provide a noninvasive means of monitoring both longitudinal changes in tumor burden 
and participants' mutational profiles. The effects of ADCs on ctDNA and associations with 

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response are not fully elucidated. ctDNA will be sequenced along with tumor sequencing and will 
be further characterized for other mutations including TROP2 gene.
5.2.3.2
Next gene sequencing, whole genome sequencing and RNAseq 
Coded, linked samples will be provided to a collaborator or core lab/company for a fee-for-service 
for the next generation sequencing, RNAseq, or whole genome sequencing. Gene expressions of 
DNA repair/replication stress response and other survival pathways will be assessed using 
RNAseq analyses on freshly obtained tumor biopsy and correlated with clinical outcomes.  Whole 
genome sequencing will be performed to identify TROP2 mutations or other gene alterations and 
correlated with clinical outcome. 
5.2.3.3
TSO500
TSO500 will be performed on archival tissue samples by the laboratory of pathology to 
complement the findings from RNAseq and/or whole genome sequencing. This will be a 
hypothesis-generating and research only test.  Note that participants will not be informed of these 
results as they are research only.
5.3
STORAGE, USE, AND SHARING OF SPECIMENS AND DATA (INCLUDING FOR SECONDARY 
RESEARCH)
5.3.1
Sample Tracking and Processing
Samples will be ordered in CRIS and tracked through a Clinical Trial Data Management system. 
Should a CRIS screen not be available, the CRIS downtime procedures will be followed. Samples 
will not be sent outside NIH without appropriate approvals and/or agreements, if required.
5.3.1.1
Biospecimen Processing Core (BPC)
Samples sent to the BPC will be placed immediately on wet ice and refrigerated. The date and 
exact time of each blood draw should be recorded on the sample tube 
Please e-mail at NCIBloodcore@mail.nih.gov at least 24 hours before transporting samples (the 
Friday before is preferred).
For sample pickup, page 102-11964.
For immediate help, call 240-760-6180 (main BPC number) or, if no answer, 240-760-6190 
(main clinical pharmacology lab number).
For questions regarding sample processing, contact NCIBloodcore@mail.nih.gov.
Upon arrival in the BPC, samples will be centrifuged and the plasma transferred into cryovials 
for storage at -80 C until the time of analysis.
5.3.1.2
DTB Clinical Translational Unit
As soon as the participant is scheduled, please send an email notification to the DTB Clinical 
Translational Unit. As soon as the sample is drawn, please call the lab at 240-760-6330 to 
communicate that the sample is ready, where the sample is located, and a lab member will pick up 
the sample. 
Immediately after collection, invert the blood tubes 8-10 times. Blood samples must be kept at 
room temperature. The blood samples will be picked up by a member of the DTB Clinical 
Translational Unit. 

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5.3.2
Sample Storage and Disposition
Barcoded samples are stored in barcoded boxes according to stability requirements. Access to 
stored clinical samples is restricted. Unless other permission obtained, samples are only to be used 
for research purposes associated with this trial (as per the IRB-approved protocol) by investigators 
named on the protocol. It is the responsibility of the Principal Investigator to ensure that samples 
are being used in a manner consistent with IRB approval. 
Sample barcodes are linked to participant demographics and limited clinical information. This 
information will only be provided to investigators listed on this protocol, via registered use of a 
sample tracking database (e.g., Labmatrix). It is critical that the sample remains linked to 
participant information such as race, age, dates of diagnosis and death, and histological 
information about the tumor, to correlate results with sample characteristics.
5.3.3
Protocol Completion/Secondary Use/Sample Destruction
Any specimens remaining at the completion of the protocol will be stored indefinitely in the 
conditions described above. The study will remain open so long as sample or data analysis 
continues. All samples and data from consenting participants will be stored in identifiable format 
until they are no longer of scientific value or if a participant withdraws consent for their continued 
use, at which time they will be destroyed. 
If, at any time, a participant withdraws from the study and does not wish for their existing samples 
to be utilized, the individual must provide a written request. Following receipt of this request, the 
samples will be destroyed or returned to the participant, if so requested. The participant’s samples 
and data will be excluded from future distributions, but those which have already been distributed 
for approved research use will not be able to be retrieved. 
The PI will record any loss or unanticipated destruction of samples as a deviation. Reporting will 
be per the requirements of Section 7.2.
through a code available to the study team, will be stored indefinitely and used for secondary 
research, including genetic research. Furthermore, the data and/or specimens, may be shared with 
other investigators in identifiable or coded (code key not available to recipient) format for 
secondary research. Any investigator conducting secondary research in human subjects will seek 
either additional regulatory approval or exemption for research as appropriate. 
Data will also be shared in public database per the study’s data sharing plan in compliance with 
NIH policies. 
In addition, specimens/data may be anonymized and further research, including genetic research, 
conducted at the site or other institutions without participant consent. Participants will be informed 
that the possibility for this type of research exists.
5.4
SAMPLES FOR GENETIC/GENOMIC ANALYSIS
5.4.1
Description of the scope of genetic/genomic analysis
One of the exploratory endpoints of this protocol is to characterize mutations which predict 
response and changes associated with the development of chemoresistance. To this end, whole and 
targeted exome sequencing will be performed on tumor samples collected pre-treatment, on-
treatment and/or post-progression. Genetic/genomic analysis will be performed by the core 
lab/company for a fee-for-service. 

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5.4.2
Description of how privacy and confidentiality of medical information/biological 
specimens will be maximized.
Initially the samples of each participant will be barcoded. At no time will participant’s names be 
used on the blood and tissue samples. Sometimes, because a group collaboration or journal policy 
requires it, a subject’s genetic data will be deposited in a database such as dbGaP. Although there 
is controlled access to such a database, such a submission carries theoretical risks of revealing the 
identity of the subject. This is discussed in the consent.
5.4.3
Management of Results
Whole genome/exome sequencing on this study is limited to tumor samples.  No germline whole 
genome sequencing is performed; therefore, it is not feasible to return secondary findings.  If we 
encounter a medically significant incidental finding, we may coordinate with the IRB, the ethics 
consult service, and the genetic consult service to explore on a case-by-case basis.
6
DATA COLLECTION AND EVALUATION 
6.1
DATA COLLECTION
The PI will be responsible for overseeing entry of data into a 21 CFR Part 11-compliant data 
capture system provided by the NCI CCR and ensuring data accuracy, consistency and timeliness. 
Principal Investigator, associate investigators/research nurses and/or a contracted data manager 
will assist with the data management efforts.  Primary and final analyzed data will have identifiers 
so that research data can be attributed to an individual human subject participant.
All adverse events (AEs), including clinically significant abnormal findings on laboratory 
evaluations, regardless of severity, will be followed until return to baseline or stabilization of 
event. 
Document AEs from the first study intervention, Study Day 1 through 30 days after the subject 
received the last product administration. Beyond 30 days after the last intervention, only adverse 
events which are serious and related to the study intervention need to be recorded.
An abnormal laboratory value will be recorded in the database as an AE only if the laboratory 
abnormality is characterized by any of the following:
•
Results in discontinuation from the study
•
Is associated with clinical signs or symptoms
•
Requires treatment or any other therapeutic intervention
•
Is associated with death or another serious adverse event, including hospitalization.
•
Is judged by the Investigator to be of significant clinical impact
•
If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the test drug and about the 
participant’s outcome.
The PI (or designee) evaluation of each AE not captured in the clinical database determining that 
it meets the criteria above will be documented in the source documents. Note: the investigator 

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performing the assessment must be a clinician licensed to diagnose and listed on the FDA Form 
1572.
End of study procedures: Data will be stored according to HHS, FDA regulations, and NIH 
Intramural Records Retention Schedule as applicable. 
6.2
PUBLICATION AND DATA SHARING POLICY
6.2.1
NIH Data Management and Sharing Policy and NIH Genomic Data Sharing Policy 
Compliance
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies 
to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated 
with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic 
data sharing. 
This study will comply with the NIH Genomic Data Sharing (GDS) Policy, which applies to all 
new and ongoing NIH IRP-funded research, as of January 25, 2015, that generates large-scale 
human or non-human genomic data, as well as the use of these data for subsequent research. Large-
scale data include genome-wide association studies (GWAS), single nucleotide polymorphisms 
(SNP) arrays, and genome sequence, transcriptomic, epigenomic, and gene expression data.
Therefore, unlinked genomic data will be deposited in public genomic databases such as dbGaP 
in compliance with the NIH Genomic Data Sharing Policy.
6.2.2
NIH Public Access Policy Compliance
This study will comply with the NIH Public Access Policy, which ensures that the public has 
access to the published results of NIH funded research. It requires scientists to submit final peer-
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication.  
6.3
RESPONSE CRITERIA
For the purposes of this study, participants should be re-evaluated for response as noted in Section 
3.1. In addition to a baseline scan, confirmatory scans should also be obtained within 8 weeks (not 
less than 4 weeks) following initial documentation of objective response.
Response and progression will be evaluated in this study using the new international criteria 
proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline 
(version 1.1) [101]. Changes in the largest diameter (unidimensional measurement) of the tumor 
lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST 
criteria.
6.3.1
Disease Parameters
Measurable disease:  Measurable lesions are defined as those that can be accurately measured in 
at least one dimension (longest diameter to be recorded) as: 
•
By chest x-ray: >20 mm; 
•
By CT scan: 
o
Scan slice thickness 5 mm or under: as >10 mm
o
Scan slice thickness >5 mm: double the slice thickness 

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•
With calipers on clinical exam: >10 mm.  
All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters).
Malignant lymph nodes. To be considered pathologically enlarged and measurable, a lymph node 
must be >15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended 
to be no greater than 5 mm). At baseline and in follow-up, only the short axis will be measured 
and followed.
Non-measurable disease. All other lesions (or sites of disease), including small lesions (longest 
diameter <10 mm or pathological lymph nodes with ≥10 to <15 mm short axis), are considered 
non-measurable disease. Bone lesions, leptomeningeal disease, ascites, pleural/pericardial 
effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not 
followed by CT or MRI), are considered as non-measurable.
Note: Cystic 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 participant, these are preferred for selection as target lesions.
Target lesions. All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in 
total, representative of all involved organs, should be identified as target lesions and recorded and 
measured at baseline. Target lesions should be selected on the basis of their size (lesions with the 
longest diameter), be representative of all involved organs, but in addition should be those that 
lend themselves to reproducible repeated measurements. It may be the case that, on occasion, the 
largest lesion does not lend itself to reproducible measurement in which circumstance the next 
largest lesion which can be measured reproducibly should be selected. A sum of the diameters 
(longest for non-nodal lesions, short axis for nodal lesions) for all target lesions will be calculated 
and reported as the baseline sum diameters. If lymph nodes are to be included in the sum, then 
only the short axis is added into the sum. The baseline sum diameters will be used as reference to 
further characterize any objective tumor regression in the measurable dimension of the disease.
Non-target lesions. All other lesions (or sites of disease) including any measurable lesions over 
and above the 5 target lesions should be identified as non-target lesions and should also be 
recorded at baseline. Measurements of these lesions are not required, but the presence, absence, or 
in rare cases unequivocal progression of each should be noted throughout follow-up. 
6.3.2
Methods for Evaluation of Measurable Disease
All measurements should be taken and recorded in metric notation using a ruler or calipers. All 
baseline evaluations should be performed as closely as possible to the beginning of treatment and 
never more than 4 weeks before the beginning of the treatment.
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is 
preferred to evaluation by clinical examination unless the lesion(s) being followed cannot be 
imaged but are assessable by clinical exam.

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Clinical lesions: Clinical lesions will only be considered measurable when they are superficial 
(e.g., skin nodules and palpable lymph nodes) and 10 mm diameter as assessed using calipers 
(e.g., skin nodules). In the case of skin lesions, documentation by color photography, including a 
ruler to estimate the size of the lesion, is recommended. 
Chest x-ray: Lesions on chest x-ray are acceptable as measurable lesions when they are clearly 
defined and surrounded by aerated lung. However, CT is preferable. 
Conventional CT and MRI: This guideline has defined measurability of lesions on CT scan based 
on the assumption that CT slice thickness is 5 mm or less. If CT scans have slice thickness greater 
than 5 mm, the minimum size for a measurable lesion should be twice the slice thickness. MRI is 
also acceptable in certain situations (e.g. for body scans).
Use of MRI remains a complex issue. MRI has excellent contrast, spatial, and temporal resolution; 
however, there are many image acquisition variables involved in MRI, which greatly impact image 
quality, lesion conspicuity, and measurement. Furthermore, the availability of MRI is variable 
globally. As with CT, if an MRI is performed, the technical specifications of the scanning 
sequences used should be optimized for the evaluation of the type and site of disease. Furthermore, 
as with CT, the modality used at follow-up should be the same as was used at baseline and the 
lesions should be measured/assessed on the same pulse sequence. It is beyond the scope of the 
RECIST guidelines to prescribe specific MRI pulse sequence parameters for all scanners, body 
parts, and diseases. Ideally, the same type of scanner should be used and the image acquisition 
protocol should be followed as closely as possible to prior scans. Body scans should be performed 
with breath-hold scanning techniques, if possible.
PET-CT: At present, the low dose or attenuation correction CT portion of a combined PET-CT is 
not always of optimal diagnostic CT quality for use with RECIST measurements. However, if the 
site can document that the CT performed as part of a PET-CT is of identical diagnostic quality to 
a diagnostic CT (with IV and oral contrast), then the CT portion of the PET-CT can be used for 
RECIST measurements and can be used interchangeably with conventional CT in accurately 
measuring cancer lesions over time. Note, however, that the PET portion of the CT introduces 
additional data which may bias an investigator if it is not routinely or serially performed.
Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement. Ultrasound examinations cannot be reproduced in their entirety for 
independent review at a later date and, because they are operator dependent, it cannot be 
guaranteed that the same technique and measurements will be taken from one assessment to the 
next. If new lesions are identified by ultrasound in the course of the study, confirmation by CT or 
MRI is advised. If there is concern about radiation exposure at CT, MRI may be used instead of 
CT in selected instances.
Endoscopy, Laparoscopy: The utilization of these techniques for objective tumor evaluation is not 
advised. However, such techniques may be useful to confirm complete pathological response when 
biopsies are obtained or to determine relapse in trials where recurrence following complete 
response (CR) or surgical resection is an endpoint.
Tumor markers: Tumor markers alone cannot be used to assess response. If markers are initially 
above the upper normal limit, they must normalize for a participant to be considered in complete 
clinical response. Specific guidelines for both CA-125 response (in recurrent ovarian cancer) and 
PSA response (in recurrent prostate cancer) have been published[102, 103]. In addition, the 

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Gynecologic Cancer Intergroup has developed CA-125 progression criteria which are to be 
integrated with objective tumor assessment for use in first-line trials in ovarian cancer [104].
Cytology, Histology: These techniques can be used to differentiate between partial responses (PR) 
and complete responses (CR) in rare cases (e.g., residual lesions in tumor types, such as germ cell 
tumors, where known residual benign tumors can remain).
The cytological confirmation of the neoplastic origin of any effusion that appears or worsens 
during treatment when the measurable tumor has met criteria for response or stable disease is 
mandatory to differentiate between response or stable disease (an effusion may be a side effect of 
the treatment) and progressive disease.
FDG-PET: While FDG-PET response assessments need additional study, it is sometimes 
reasonable to incorporate the use of FDG-PET scanning to complement CT scanning in assessment 
of progression (particularly possible 'new' disease). New lesions on the basis of FDG-PET imaging 
can be identified according to the following algorithm: 
a.
Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD 
based on a new lesion.
b. No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-
PET at follow-up corresponds to a new site of disease confirmed by CT, this is PD. If 
the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG-
PET scan). If the positive FDG-PET at follow-up corresponds to a pre-existing site of 
disease on CT that is not progressing on the basis of the anatomic images, this is not 
PD.
c.
FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy 
in cases where a residual radiographic abnormality is thought to represent fibrosis or 
scarring. The use of FDG-PET in this circumstance should be prospectively described 
in the protocol and supported by disease-specific medical literature for the indication. 
However, it must be acknowledged that both approaches may lead to false positive CR 
due to limitations of FDG-PET and biopsy resolution/sensitivity.
Note: A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an uptake greater 
than twice that of the surrounding tissue on the attenuation corrected image.
6.3.3
Response Criteria
6.3.3.1
Evaluation of Target Lesions
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking 
as reference the baseline sum of diameters.
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest 
on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute 

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increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered 
progressions).
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum of diameters while on study.
6.3.3.2
Evaluation of Non-Target Lesions
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor 
marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
Note: If tumor markers are initially above the upper normal limit, they must normalize for a 
participant to be considered in complete clinical response.
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits.
Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression 
of existing non-target lesions. Unequivocal progression should not normally trump target lesion 
status. It must be representative of overall disease status change, not a single lesion increase.
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the treating 
physician should prevail in such circumstances, and the progression status should be confirmed at 
a later time by the review panel (or Principal Investigator).
6.3.3.3
Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the treatment until disease 
progression/recurrence (taking as reference for progressive disease the smallest measurements 
recorded since the treatment started). The participant's best response assignment will depend on 
the achievement of both measurement and confirmation criteria.
For Participants with Measurable Disease (i.e., Target Disease)
Target 
Lesions
Non-Target 
Lesions
New 
Lesions
Overall 
Response
Best Overall Response when 
Confirmation is Required*
CR
CR
No
CR
≥ 4 wks. Confirmation**
CR
Non-CR/Non-
PD
No
PR
CR
Not evaluated
No
PR
PR
Non-CR/Non-
PD/not 
evaluated
No
PR
≥ 4 wks. Confirmation**
SD
Non-CR/Non-
PD/not 
evaluated
No
SD
Documented at least once ≥ 4 
wks. from baseline**
PD
Any
Yes or 
No
PD
Any
PD***
Yes or 
No
PD
Any
Any
Yes
PD
no prior SD, PR or CR

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Target 
Lesions
Non-Target 
Lesions
New 
Lesions
Overall 
Response
Best Overall Response when 
Confirmation is Required*
*
See RECIST 1.1 manuscript for further details on what is evidence of a new lesion.
**
Only for non-randomized trials with response as primary endpoint.
***
In exceptional circumstances, unequivocal progression in non-target lesions may be 
accepted as disease progression.
Note:
Participants with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be 
reported as “symptomatic deterioration.” Every effort should be made to document the 
objective progression even after discontinuation of treatment.
6.3.4
Duration of Response (DOR)
Duration of overall response: The duration of overall response is measured from the time 
measurement criteria are met for CR or PR (whichever is first recorded) until the first date that 
recurrent or progressive disease is objectively documented (taking as reference for progressive 
disease the smallest measurements recorded since the treatment started).
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that progressive disease is objectively documented.
Duration of stable disease: Stable disease is measured from the start of the treatment until the 
criteria for progression are met, taking as reference the smallest measurements recorded since the 
treatment started, including the baseline measurements. 
6.3.5
Progression-Free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, 
whichever occurs first.
6.3.6
Overall survival (OS)
OS is defined as the length of time from start of treatment until death from any cause.
6.3.7
Response Review
Tumor measurements will be performed by the CCR radiologist.
6.4
TOXICITY CRITERIA
The following adverse event management guidelines are intended to ensure the safety of each 
participant while on the study.  The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE 
reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 5.0. 
A copy of the CTCAE version 5.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm).  
7
NIH REPORTING REQUIREMENTS / DATA AND SAFETY MONITORING PLAN
7.1
DEFINITIONS
Please refer to definitions provided in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/hrpp-policy-guidelines/.

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7.2
OHSRP OFFICE OF COMPLIANCE AND TRAINING / IRB REPORTING
7.2.1
Expedited Reporting 
Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 
802 Non-Compliance Human Subjects Research found at: https://irbo.nih.gov/hrpp-policy-
guidelines/. Note: Only IND Safety Reports that meet the definition of an unanticipated problem 
or present new information that might affect the willingness of participants to enroll or remain on the 
study will need to be reported per these policies.
7.2.2
IRB Requirements for PI Reporting at Continuing Review
Please refer to the reporting requirements in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/hrpp-policy-guidelines/. 
7.2.3
NCI Clinical Director Reporting 
Problems expeditiously reviewed by the OHSRP in the NIH eIRB system will also be reported to 
the NCI Clinical Director; therefore, a separate submission for these reports is not necessary.
In addition to those reports, all deaths that occur within 30 days after receiving a research 
intervention should be reported via email unless they are due to progressive disease.  
To report these deaths, please send an email describing the circumstances of the death to 
NCICCRQA@mail.nih.gov within one business day of learning of the death.
7.3
NIH REQUIRED DATA AND SAFETY MONITORING PLAN
7.3.1
Principal Investigator/Research Team 
The clinical research team will meet on a regular basis (weekly) when patients are being actively 
treated on the trial to discuss each patient. Decisions about dose level enrollment and dose 
escalation if applicable will be made based on the toxicity data from prior patients. 
All data will be collected in a timely manner and reviewed by the PI or a lead AI. Events meeting 
requirements for expedited reporting as described in Section 7.2.1 will be submitted within the 
appropriate timelines.  
The PI will review adverse event and response data on each patient to ensure safety and data 
accuracy. The PI will personally conduct or supervise the investigation and provide appropriate 
delegation of responsibilities to other members of the research staff.
8
SPONSOR PROTOCOL/SAFETY REPORTING
8.1
DEFINITIONS
8.1.1
Adverse Event 
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product (ICH E6 (R2)).

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8.1.2
Serious Adverse Event (SAE)
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following:
•
Death,
•
A life-threatening adverse event (see Section 8.1.3)
•
Inpatient hospitalization or prolongation of existing hospitalization
o
A hospitalization/admission that is pre-planned (i.e., elective or scheduled surgery 
arranged prior to the start of the study), a planned hospitalization for pre-existing 
condition, or a procedure required by the protocol, without a serious deterioration in 
health, is not considered a serious adverse event.
o
A hospitalization/admission that is solely driven by non-medical reasons (e.g., 
hospitalization for patient or subject convenience) is not considered a serious adverse 
event. 
o
Emergency room visits or stays in observation units that do not result in admission to 
the hospital would not be considered a serious adverse event. The reason for seeking 
medical care should be evaluated for meeting one of the other serious criteria.
•
Persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions
•
A congenital anomaly/birth defect
•
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition.
8.1.3
Life-threatening 
An adverse event or suspected adverse reaction is considered "life-threatening" if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a 
more severe form, might have caused death. (21CFR312.32)
8.1.4
Severity
The severity of each Adverse Event will be assessed utilizing the CTCAE version 5.
8.1.5
Relationship to Study Product
All AEs will have their relationship to study product assessed using the terms: related or not 
related. 
•
Related – There is a reasonable possibility that the study product caused the adverse event. 
Reasonable possibility means that there is evidence to suggest a causal relationship 
between the study product and the adverse event.
•
Not Related – There is not a reasonable possibility that the administration of the study 
product caused the event.

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8.2
ASSESSMENT OF SAFETY EVENTS
AE information collected will include event description, date of onset, assessment of severity and 
relationship to study product and alternate etiology (if not related to study product), date of 
resolution of the event, seriousness and outcome. The assessment of severity and relationship to 
the study product will be done only by those with the training and authority to make a diagnosis 
and listed on the Form FDA 1572 as the site principal investigator or sub-investigator.
AEs occurring during the collection and reporting period will be documented appropriately 
regardless of relationship. AEs will be followed through resolution.
SAEs will be:
•
Assessed for severity and relationship to study product and alternate etiology (if not related 
to study product) by a licensed study physician listed on the Form FDA 1572 as the 
principal investigator or sub-investigator.
•
Recorded on the appropriate SAE report form, the medical record and captured in the 
clinical database.
•
Followed through resolution by a licensed study physician listed on the Form FDA 1572 
as the principal investigator or sub-investigator.
With the exception of any listed in Section 8.4, reporting is required for all serious adverse events 
occurring from the first study intervention, Study Day 1, through 30 days after the subject received 
the last product administration. After 30 days, only adverse events which are serious and related 
to the study investigational agent need to be reported. 
8.3
REPORTING OF SERIOUS ADVERSE EVENTS
Any AE that meets protocol-defined serious criteria that require expedited reporting must be 
submitted immediately (within 24 hours of awareness) to OSRO Safety using the CCR SAE report 
form. Any exceptions to the expedited reporting requirements are found in Section 8.4 .
SAE reports will be submitted to the Center for Cancer Research (CCR) at: 
OSROSafety@mail.nih.gov and to the CCR PI and study coordinator. CCR SAE report form and 
instructions can be found at: https://nih.sharepoint.com/:u:/r/sites/NCI-CCR-OCD-
Communications/SitePages/Forms-and-Instructions.aspx?csf=1&web=1&e=uWBXtI
Following the assessment of the SAE by OSRO, other supporting documentation of the event may 
be requested by the OSRO Safety and should be provided as soon as possible.
8.4
WAIVER OF EXPEDITED REPORTING TO CCR
As disease progression and death are part of the study objectives (OS, PFS, DOR), and captured 
as an endpoint in this study, they will not be reported in expedited manner to the sponsor. However, 
if there is evidence suggesting a causal relationship between the study drug and the event, report 
the event in an expedited manner according to Section 8.3.
8.5
SAFETY REPORTING CRITERIA TO THE PHARMACEUTICAL COLLABORATORS
Reporting will be per the collaborative agreement. 

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8.6
REPORTING PREGNANCY 
All required pregnancy reports/follow-up to OSRO will be submitted to: 
OSROSafety@mail.nih.gov and to the CCR PI and study coordinator. Forms and instructions 
can be found here: https://nih.sharepoint.com/:u:/r/sites/NCI-CCR-OCD-
Communications/SitePages/Forms-and-Instructions.aspx?csf=1&web=1&e=uWBXtI
8.6.1
Maternal exposure
Participants should refrain from becoming pregnant during the study and for 6 months after the 
last dose of SG.
If a participant becomes pregnant during the course of the study, the study treatment should be 
discontinued immediately, and the pregnancy reported to the Sponsor no later than 24 hours of 
when the Investigator becomes aware of it. The Investigator should notify the Sponsor no later 
than 24 hours of when the outcome of the pregnancy becomes known.
Pregnancy itself is not regarded as an SAE. However, congenital abnormalities or birth defects 
and spontaneous miscarriages that meet serious criteria (Section 8.1.2) should be reported as SAEs. 
The outcome of all pregnancies occurring from the date of the first dose of study therapy until 6 
months after the last dose of study therapy should be followed up and documented.
8.7
REGULATORY REPORTING FOR STUDIES CONDUCTED UNDER CCR-SPONSORED IND
Following notification from the investigator, CCR, the IND sponsor, will report any suspected 
adverse reaction that is both serious and unexpected. CCR will report an AE as a suspected adverse 
reaction only if there is evidence to suggest a causal relationship between the study product and 
the adverse event. CCR will notify FDA and all participating investigators (i.e., all investigators 
to whom the sponsor is providing drug under its INDs or under any investigator’s IND) in an IND 
safety report of potential serious risks from clinical trials or any other source, as soon as possible, 
in accordance to 21 CFR Part 312.32. 
All serious events will be reported to the FDA at least annually in a summary format.
8.8
SPONSOR PROTOCOL DEVIATION REPORTING
A Protocol Deviation is defined as any non-compliance with the clinical trial Protocol, Manual of 
Operational Procedures (MOP) and other Sponsor approved study related documents, GCP, or 
protocol-specific procedural requirements on the part of the participant, the Investigator, or the 
study site staff inclusive of site personnel performing procedures or providing services in support 
of the clinical trial.
It is the responsibility of the study Staff to document any protocol deviation identified by the Staff 
or the site Monitor in the CCR Protocol Deviation Tracking System (PDTS) online application. 
The entries into the PDTS online application should be timely, complete, and maintained per CCR 
PDTS user requirements. 
In addition, any deviation to the protocol should be documented in the participant’s source records 
and reported to the reviewing IRB per their guidelines. OSRO required protocol deviation 
reporting is consistent with E6(R2) GCP: Integrated Addendum to ICH E6(R1): 4.5 Compliance 
with Protocol; 5.18.3 (a), and 5.20 Noncompliance; and ICH E3 16.2.2 Protocol deviations.

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9
CLINICAL MONITORING 
Clinical site monitoring is conducted to ensure:
•
that the rights of the participants are protected; 
•
that the study is implemented per the approved protocol, Good Clinical Practice and 
standard operating procedures; and 
•
the quality and integrity of study data and data collection methods are maintained. 
Monitoring for this study will be performed by NCI CCR Office of Sponsor and Regulatory 
Oversight (OSRO) and Regulatory Oversight Support (SROS) Services contractor. Clinical site 
monitoring activities will be based on OSRO standards, FDA Guidance E6(R2) Good Clinical 
Practice: Integrated Addendum to ICH E6(R1) March 2018, and applicable regulatory 
requirements.
Details of clinical site monitoring will be documented in a Clinical Monitoring Plan (CMP) 
developed by OSRO. CMPs will be protocol-specific, risk-based and tailored to address human 
subject protections and integrity of the study data. OSRO will determine the intensity and 
frequency of monitoring based on several factors, including study type, phase, risk, complexity, 
expected enrollment rate, and any unique attributes of the study and the site. The Sponsor will 
conduct a periodic review of the CMP to confirm the plan's continued appropriateness. A change 
to the protocol, significant or pervasive non-compliance with GCP, or the protocol may trigger 
CMP updates.
OSRO SROS Monitoring visits and related activities will be conducted throughout the life cycle 
of each protocol. The first activity is before the study starts to conduct a Site Assessment Visit 
(SAV) (as warranted), followed by a Site Initiation Visit (SIV), Interim Monitoring Visit(s) 
(IMVs), and a study Close-Out Visit (COV).
Some monitoring activities may be performed remotely, while others will occur at the study site(s). 
Monitoring visit reports will describe visit activities, observations, and associated action items or 
follow-up required for resolution of any issues, discrepancies, or deviations. Monitoring reports 
will be distributed to the study PI, NCI CCR QA, CCR Protocol Support Office, Coordinating 
Center, and the Sponsor regulatory file.
The site Monitor will inform the study team of any deviations observed during monitoring visits. 
If unresolved, the Monitor will request that the site Staff enter the deviations in the CCR Protocol 
Deviation Tracking System (PDTS) for deviation reporting to the Sponsor and as applicable per

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10 STATISTICAL CONSIDERATIONS  
10.1 OBJECTIVES AND ENDPOINTS
OBJECTIVES
ENDPOINTS
JUSTIFICATION FOR 
ENDPOINTS
Primary
To determine the ORR of SG in 
participants with recurrent 
gynecological malignancies, 
calculated for each individual tumor 
histology by RECIST v1.1
ORR (RECIST v1.1) assessed by 
radiographical evaluation i.e., 
CT/MRI every 9 weeks (+/- 1 week) 
for the first year and then every 12 
weeks (+/-1 week) until PD or up to 5 
years and at EOT which occurs within 
14 days after the end of therapy.  
Standard endpoint for 
phase 2 cancer clinical 
trials. Success of 
regimens will be 
determined by these 
endpoints.
Secondary
To determine the safety of SG 
Identify adverse events (AE) per 
CTCAE v5.0, by type and grade of 
toxicity on Days 1, 8, and 15 of each 
cycle, at EOT which occurs within 14 
days after the end of therapy, and 30 
days after the end of treatment. 
Beyond 30 days after the last 
intervention, only adverse events 
which are serious and related to the 
study intervention will be assessed.
Safety is a standard 
endpoint for clinical 
trials (collecting 
information on all 
major organ function 
and observed toxicity, 
if any, to determine 
prominent toxicity to 
advise safety).
To determine the PFS of 
participants receiving SG
Participants will be assessed for PFS 
by CT CAP at every restaging every 9 
weeks for the first year and then every 
12 weeks until PD or up to 5 years 
and at EOT which occurs within 14 
days after the end of therapy.
To determine the OS of participants 
receiving SG
Participants will be assessed for OS 
from start of treatment. OS will be 
collected on Days 1, 8, and 15 of each 
cycle for up to 5 years, at EOT which 
occurs within 14 days after the end of 
therapy, 30-day safety visit and every 
6 months during follow up for up to 
10 years.
Standard endpoints for 
correlative studies. 
These endpoints will 
explore changes within 
timepoints as stipulated 
within the protocol to 
understand the effect of 
SG.

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OBJECTIVES
ENDPOINTS
JUSTIFICATION FOR 
ENDPOINTS
To determine the median DoR of 
SG 
Participants will be followed until 
progression after completion of study 
therapy and assessed by CT CAP very 
9 weeks for the first year and then 
every 12 weeks until PD or up to 5 
years and at EOT which occurs within 
14 days after the end of therapy. 
Exploratory 
To evaluate UGT1A1*28 allele as a 
predictive marker for 
gastrointestinal and hematologic 
toxicities
UGT1A1 allele genotype will be 
measured at baseline.
UGT1A1 genotype 
influences the rate of 
metabolism of SN38 
and has been shown to 
correlate with toxicity 
in prior trials of SG. 
This data can guide 
management of toxicity 
for participants in this 
study and future 
clinical trials.
To evaluate the concordance (or 
discordance) of TROP2 expression 
between archival tissues and 
pretreatment fresh biopsies 
The concordance of TROP2 protein 
expression levels by IHC (median H-
scores) between archival tissue 
samples and fresh pretreatment 
biopsy 
Preclinical data suggest 
TROP2 expression may 
change (either decrease 
or increase) over time 
but most clinical trials 
use archival tissue 
samples to assess 
TROP2 expression. 
Our data on the 
concordance (or 
discordance) of TROP2 
expression between 
archival and 
pretreatment samples 
can help understand 
SG’s biology in 
participants.
To identify mutations of TROP2 
gene (TACSTD2) in tumors with 
resistance against SG
TROP2 surface protein expression 
from tumor tissue will be measured at 
baseline (i.e., prior to study treatment) 
Correlates of TROP2 
expression, specific 
transcriptomic, and/or 
mutational profiles and 
response can guide 
appropriate selection of 
participants in future 
study if the primary 
objective is met.

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OBJECTIVES
ENDPOINTS
JUSTIFICATION FOR 
ENDPOINTS
To investigate systemic 
pharmacodynamic biomarkers 
before and after SG treatment (i.e., 
ctDNA, CTC, and γH2AX 
expression)
Potential PD or predictive biomarker 
endpoints of DNA damage response 
pathways from blood will be 
measured at baseline, C1D8, C3D1, 
and EOT which occurs within 14 days 
after the end of therapy and from 
tumor tissue at baseline and EOT 
which occurs within 14 days after the 
end of therapy.
Determine baseline and 
treatment expression of 
biomarkers of response.
10.2 STATISTICAL HYPOTHESIS
Treatment with SG will result in a higher ORR than standard-of-chemotherapy regimen (> 15% 
ORR).
10.3 SAMPLE SIZE DETERMINATION
The sample size calculation is determined based on the same calculations for each of the three 
cohorts separately. In participants with recurrent/metastatic ovarian cancer, endometrial cancer, 
and cervical cancer, previous studies suggest that response ranges from approximately 10-15% 
using single agent chemotherapy [25, 26], which is what we aim to improve upon.
For each of cohorts 1, 2, and 3, we will conduct separate phase II studies. For each cohort, the 
objective is to rule out an unacceptably low ORR (CR + PR) of 15% (p0 = 0.15) in favor of an 
improved ORR (CR + PR) of 35% (p1 = 0.35). Using a Simon two-stage minimax design, 
assuming a power of 80% and a type 1 error rate (one-sided) of 10%, the first stage will enroll 10 
participants. If during the first stage, 0 or 1 of the first 10 participants have a response, the cohort 
will stop early for futility. If 2 or more of the first 10 participants have a response, 12 additional 
participants will be enrolled in the cohort, for a total of 22 participants in that cohort. 
In order to ensure that enrollment to the second stage is warranted, a temporary pause may be 
employed after accrual to the first stage if additional follow-up time is needed to assess the number 
of responses. If after the second stage, there are 6 or more participants with a response out of 22 
(6/22= 27.3%) participants, the treatment would be deemed interesting for further study in later 
trials. If 2 to 5 out of 22 participants have a response, then further investigation of the treatment 
would not be warranted.
The trial may accrue up to 22 + 22 + 22 = 66 evaluable participants if all three cohorts proceed to 
the second stage. To allow for a small number of inevaluable participants (9) and screen failures 
(20), the accrual ceiling will be set at 95. It is anticipated that up to 2-3 participants per month may 
be enrolled on this trial. Accrual is therefore expected to be completed within 3 years.
10.4 POPULATION FOR ANALYSIS 
10.4.1 Evaluable for toxicity
Any participant receiving at least one dose of either agent will be evaluable for toxicity.
10.4.2 Evaluable for objective response
Only those participants who have measurable disease present at baseline, have received at least 
one cycle of therapy, and have had their disease re-evaluated at the restaging scans will be 

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considered evaluable for response. These participants will have their response classified according 
to the definitions stated in Section 6.3. (Note: Participants who exhibit objective disease 
progression before their scheduled first restaging scans may be considered evaluable).
10.5 STATISTICAL ANALYSES
10.5.1 General approach
ORR will be reported by disease cohort along with a confidence interval. 
Toxicities will be reported by grade and type; PFS, and OS will be reported by cohort along with 
a confidence interval.
10.5.2 Analysis of the Primary Endpoint
ORR (the fraction of PR or CR) will be calculated along with a 95% confidence interval for each 
cohort. 
The proportion of participants who achieve a response will be reported separately for each cohort, 
along with 95% confidence intervals (Clopper-Pearson).
10.5.3 Analysis of the Secondary Endpoints
10.5.3.1 Safety 
Safety will be reported by describing AE per CTCAE v5.0, by type and grade of toxicity, as 
detailed in Section 6.3.  
10.5.3.2 Clinical Efficacy
The assessment of clinical activity as determined by:
•
DOR will be calculated by the Kaplan-Meier method, starting at date response was 
identified until progression or the response is declared to have ended, if the participants 
have a PR or CR. The median DOR will be reported along with a 95% confidence interval 
by cohort.
•
PFS will be calculated from on-study date until date of progression or death without 
progression, using the Kaplan-Meier method by cohort. The median PFS will be reported 
along with a 95% confidence interval by cohort.
•
OS will be calculated from on-study date until date of 10-year follow-up, using the Kaplan-
Meier method by cohort. The ten-year OS rate, which is the percentage of people in a study 
or treatment group who are alive ten years after their initiation of the study treatment. The 
median OS will be reported along with a 95% confidence interval by cohort.
10.5.4 Safety Analyses
To assess safety in previously treated ovarian, endometrial, and cervical cancer participants, the 
toxicity grade and type will be reported for all participants treated in the three cohorts or separately 
by cohort.
10.5.5 Baseline Descriptive Statistics
Baseline demographic characteristics will be reported, separately by disease cohort.

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10.5.6 Planned Interim Analyses
Interim analyses for efficacy will be performed after the first stage of the two-stage design as 
appropriate.
Separately for each cohort, after the first restaging scan of the last evaluable participant required 
for the interim analysis, enrollment to the cohort will be halted to allow for an analysis by the study 
team. An interim analysis report will be created to document the number of responses in the first 
stage. The memo will be provided to study sponsor prior to continuation of accrual. Alternatively, 
if the required number of responses is observed before that time, the memo may be generated, 
reviewed, and provided to the study sponsor at that point without a pause in accrual.
10.5.7 Sub-Group Analyses
Analyses will be reported by cohort. Results presented in an exploratory fashion.
10.5.8 Exploratory Analyses
Planned exploratory analyses are detailed in Section 5.
Each of these will be done using descriptive methods only and reported as exploratory results. If 
any statistical tests are performed in these analyses, the results will be presented without 
adjustment for multiple comparisons but reported in the context of the number of tests performed.
11 COLLABORATIVE AGREEMENTS
11.1 COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT (CRADA) 
This study will receive SG under a CRADA with Gilead Sciences, LLC (CRADA # C-098-2024).
12 HUMAN SUBJECTS PROTECTIONS 
12.1 RATIONALE FOR SUBJECT SELECTION
Participants with relapsed/refractory ovarian, endometrial, and cervical carcinomas will be 
evaluated for participation in this study. Individuals of any race or ethnic group will be eligible for 
this study. Eligibility assessment will be based solely on the participant’s medical status.
Pregnant participants are excluded from this study because SG is an investigational agent with the 
potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk 
for adverse events in nursing infants secondary to treatment of the mother with SG, nursing should 
be discontinued or not started until 1 month after the last dose of study drug.
12.2 PARTICIPATION OF CHILDREN
Because no dosing adverse event data are currently available on the use of SG in subjects <18 
years of age, children are excluded from this study.
12.3 RISK/BENEFIT ASSESSMENT
12.3.1 Known Potential Risks 
12.3.1.1 Study drug
Please refer to the risks outlined in Section 13.1.2.

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12.3.1.2 Study procedures
12.3.1.2.1 Blood draws
Side effects of blood draws include pain and bruising, lightheadedness, and rarely, fainting. Up to 
83 mL of research blood may be collected at any visit but no more than 211 ml in an 8-week 
period.
12.3.1.2.2 Urine collection
No physical risks are associated with urine collection.
12.3.1.2.3 Electrocardiogram (EKG)
Some skin irritation can occur where the EKG electrodes are placed. The test is completely 
painless, and generally takes less than a minute to perform.
12.3.1.2.4 Tumor biopsy
Needle biopsy is minimally invasive and is typically a very safe procedure. Depending upon the 
site being biopsied and the type of biopsy being performed, risks can include infection of the 
biopsy site, development of a hematoma, and bleeding. Rarely more significant complications can 
occur when structures near the biopsy target are entered with the needle (e.g., puncture of lung or 
bowel). Surgical procedures for biopsy specimens will not be conducted for the sole purpose of 
research specimen collection, although when surgical biopsies are performed for clinical or 
protocol requirements, samples may be requested as part of participation on this trial. In this 
instance, no added risk is incurred. In addition, as the biopsies may be collected under CT 
guidance, subjects in this study may be exposed to radiation as discussed below.
12.3.1.2.5 Local anesthesia
Biopsies may be done under local anesthesia. Potential side effects of local anesthesia include 
drowsiness, headaches, blurred vision, twitching muscles or shivering, continuing numbness, 
weakness or pins and needles sensation.
12.3.1.2.6 General anesthesia
Risks of general anesthesia include temporary confusion and memory loss, although this is more 
common in the elderly, dizziness, difficulty passing urine, bruising or soreness from the IV drip, 
nausea and vomiting, shivering and feeling cold, sore throat due to the breathing tube.
12.3.1.2.7 CT Imaging
In addition to the radiation risks discussed below, CT scans may include the risks of an allergic 
reaction to the contrast. Participants might experience hives, itching, headache, difficulty 
breathing, increased heart rate and swelling.
12.3.1.2.8 MR imaging
Participants undergoing gadolinium enhanced MRIs may also be at risk for kidney damage. MRIs 
include the additional risk of damage to hearing.
12.3.1.2.9 Exposure to radiation
On this study, participants may receive up to 3 CT-guided biopsies and up to 7 CT scans/year. The 
total radiation dose for research purposes will be approximately 12.5 rem. The risk of getting 
cancer from the radiation exposure in this study is 1.3% and of getting a fatal cancer is 0.6%.

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12.3.2 Known Potential Benefits
The potential benefit to a participant that goes onto study is a reduction in the bulk of their tumor 
which may or may not have favorable impact on symptoms and/or survival. Long range potential 
benefits of this study will build on knowledge and the science used to develop therapies for future 
cancer participants.
12.3.3 Assessment of Potential Risks and Benefits
Participants who have relapsed/refractory ovarian, endometrial, and cervical carcinomas may 
benefit from receiving SG monotherapy, which they would otherwise not obtain in a standard of 
care setting. Immediate potential benefits include potential response to tumor progression, 
palliation of symptoms, and improved outcomes. A number of clinically appropriate strategies to 
minimize risk to participants have been built into the protocol through the means of 
inclusion/exclusion criteria, monitoring strategies, and management guidelines. Overall, the 
potential benefits of SG for this group of participants outweigh the risks associated with the 
proposed entry into this protocol.
12.4 CONSENT PROCESS AND DOCUMENTATION
The informed consent document will be provided as a physical or electronic document to the 
participant as applicable for review prior to consenting. A designated study investigator will 
carefully explain the procedures and tests involved in this study, and the associated risks, 
discomforts and benefits. In order to minimize potential coercion, as much time as is needed to 
review the document will be given, including an opportunity to discuss it with friends, family 
members and/or other advisors, and to ask questions of any designated study investigator. A signed 
informed consent document will be obtained prior to entry onto the study. 
The initial consent process as well as re-consent, when required, may take place in person or 
remotely (e.g., via telephone or other site approved remote platforms used in compliance with local 
policy, including HRPP Policy 303) per discretion of the designated study investigator and with 
the agreement of the participant. Whether in person or remote, the privacy of the subject will be 
maintained. Consenting investigators (and participant when in person) will be located in a private 
area (e.g., clinic consult room). When consent is conducted remotely, the participant will be 
informed of the private nature of the discussion and will be encouraged to relocate to a more private 
setting if needed. 
Consent will be documented with required signatures on the physical document (which includes 
the printout of an electronic document sent to participant). When required, witness signature will 
be obtained similarly as described for the investigator and participant.
Manual (non-electronic) signature on electronic document:
When a manual signature on an electronic document is used for the documentation of consent 
at the NIH Clinical Center, this study will use the following to obtain the required signatures:
•
Adobe platform (which is not 21 CFR Part 11 compliant); or,
•
iMedConsent platform (which is 21 CFR Part 11 compliant)
During the consent process, participants and investigators will view individual copies of the 
approved consent document on screens at their respective locations (if remote consent); the 
same screen may be used when in the same location but is not required.

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Both the investigator and the participant will sign the document using a finger, stylus or mouse.
Note: Refer to the CCR SOP PM-2, Obtaining and Documenting the Informed Consent Process 
for additional information (e.g., verification of participant identity when obtaining consent 
remotely) found at: https://nih.sharepoint.com/sites/NCI-CCR-OCD-
Communications/SitePages/OEC-Administrative---Clinical-Research-
(ADCR).aspx?Mode=Edit.REGULATORY AND OPERATIONAL CONSIDERATIONS 
12.5 STUDY DISCONTINUATION AND CLOSURE
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
investigator, funding agency, the Investigational New Drug (IND) sponsor and regulatory 
authorities. If the study is prematurely terminated or suspended, the Principal Investigator (PI) will 
promptly inform study participants, the Institutional Review Board (IRB), and sponsor and will 
provide the reason(s) for the termination or suspension. Study participants will be contacted, as 
applicable, and be informed of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to:
•
Determination of unexpected, significant, or unacceptable risk to participants
•
Demonstration of efficacy that would warrant stopping   
•
Insufficient compliance to protocol requirements
•
Data that are not sufficiently complete and/or evaluable
•
Determination that the primary endpoint has been met
•
Determination of futility
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA).
12.6 QUALITY ASSURANCE AND QUALITY CONTROL
The clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion. An individualized quality management plan 
will be developed to describe a site’s quality management. 
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical 
trial is conducted and data are generated and biological specimens are collected, documented 
(recorded), and reported in compliance with the protocol, International Council for Harmonisation 
Good Clinical Practice (ICH GCP), and applicable regulatory requirements (e.g., Good Laboratory 
Practices (GLP), Good Manufacturing Practices (GMP)). 
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities.

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12.7 CONFLICT OF INTEREST POLICY
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, persons who have a perceived conflict of interest will be required to have 
such conflicts managed in a way that is appropriate to their participation in the design and conduct 
of this trial. The study leadership in conjunction with the NIH has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest.
12.8
 CONFIDENTIALITY AND PRIVACY 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor. This confidentiality is extended to cover testing of biological samples 
and genetic tests in addition to the clinical information relating to participants. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in strict confidence. 
No information concerning the study or the data will be released to any unauthorized third party 
without prior written approval of the sponsor. 
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the sponsor, representatives of the 
Institutional Review Board (IRB), and/or regulatory agencies may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical records 
(office, clinic, or hospital) and pharmacy records for the participants in this study. The clinical 
study site will permit access to such records.
The study participant’s contact information will be securely stored at the clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by the reviewing IRB, Institutional policies, or sponsor 
requirements. 
Study participant research data which is for purposes of statistical analysis will not include the 
participant’s contact or identifying information. Rather, individual participants and their research 
data will be identified by a unique study identification number. The study data entry and study 
management systems used by the clinical sites will be secured and password protected. At the end 
of the study, all study databases will be archived at the NIH Clinical Center. 
To further protect the privacy of study participants, a Certificate of Confidentiality has been issued 
by the National Institutes of Health (NIH). This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any civil, 
criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local 
level. By protecting researchers and institutions from being compelled to disclose information that 
would identify research participants, Certificates of Confidentiality help achieve the research 
objectives and promote participation in studies by helping assure confidentiality and privacy to 
participants.

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13 PHARMACEUTICAL INFORMATION  
13.1 SACITUZUMAB GOVITECAN (IMMU-132; TRODELVY) (IND # 166593) 
13.1.1 Source/Acquisition and Accountability 
Commercial stock of SG is manufactured and provided by Gilead Sciences. The commercial 
supply will be delivered directly to the NIH Pharmacy. Expired or unused product will be returned 
to the manufacturer or disposed of according to standard site procedures based on agreement 
between the manufacturer and the site. 
13.1.2 Toxicity 
Per the investigator brochure, the most common adverse reactions (incidence > 25%) occurring 
with SG are decreased leukocyte count, decreased neutrophil count, thrombocytopenia, decreased 
hemoglobin, diarrhea, nausea, fatigue, vomiting, alopecia, anemia, constipation, decreased 
appetite, increased glucose, decreased albumin, decreased creatinine clearance, increased alkaline 
phosphatase, decreased magnesium, decreased potassium, and decreased sodium. Serious 
reactions include diarrhea and neutropenia. 
Please see package insert for additional information.
13.1.3 Formulation and Preparation 
Please see package insert.
13.1.4 Stability and Storage 
Please see package insert.
13.1.5 Administration Procedures
SG will be administered on this study as described in Section 3.2. 
SG should be administered in a setting that allows for immediate access to an intensive care unit 
and administration of therapy for anaphylaxis. 
Do not administer as an IV push or bolus. Do not co-administer other drugs through the same 
intravenous line. 
13.1.6 Incompatibilities
Please see package insert.

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15 LIST OF ABBREVIATIONS
Abbreviation
Term
ADC
Antibody-drug conjugate
AE
Adverse Event/Adverse Experience
ALT
Alanine aminotransferase
ANC
Absolute neutrophil count
AP
Alkaline phosphatase
aPTT
Activated Partial Thromboplastin Time
AST
Aspartate aminotransferase
ATR
Ataxia telangiectasia and RAD3-Related 
ATRi
Ataxia telangiectasia and RAD3-Related inhibitor
BPC
Biospecimen Processing Core
BRCA mut
BReast CAncer gene mutant
BRCA wt
BReast CAncer gene wild-type
CAP
Chest, abdomen, and pelvis
CBC
Complete blood count
CBR
Clinical benefit rate
CCR
Center for Cancer Research
CCTV
Clinical Center TV
CFR
Code of Federal Regulations
CI
Confidence interval
CLIA
Clinical Laboratory Improvement Amendments
CMP
Clinical Monitoring Plan
CNS
Central nervous system
CONSORT
Consolidated Standards of Reporting Trials
COV
Close-out Visit
CPP
Clinical Pharmacology Program
CR
Complete Response
CRADA
Cooperative Research and Development Agreement
CRIS
Clinical research information system
CT
Computed Tomography
CTC
Circulating Tumor Cells
CTCAE
Common Terminology Criteria for Adverse Events
ctDNA
Circulating tumor DNA
CTEP
Cancer Therapy Evaluation Program
DMS
Data Management and Sharing 
DNA
Deoxyribonucleic acid
DOR
Duration of response
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic Case Report Form
EKG
Electrocardiogram
EoT
End of treatment
FDA
Food and Drug Administration

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Abbreviation
Term
FDG
Fluorodeoxyglucose
FFPE
Formalin fixed paraffin embedded
FU
Follow-up
GCP
Good Clinical Practice
G-CSF
Granulocyte – Colony Stimulating Factor
GDS
Genomic Data Sharing
GFR
Glomerular Filtration Rate
GI
Gastrointestinal
GLP
Good Laboratory Practices
GMP
Good Manufacturing Practices
GWAS
Genome-wide association studies
HAART
Highly active antiretroviral therapy
HBV
Hepatitis B virus
HCG
Human chorionic gonadotropin
HCV
Hepatitis C virus
Hgb
Hemoglobin
HGSOC
High grade serous ovarian cancer
HHS
Health and Human Services
HIV
Human immunodeficiency virus
HRD
Homologous repair deficiencies
HRPP
Human Research Protection Program
ICH
International Council for Harmonisation
ICI
Immune checkpoint inhibitor
IHC
Immunohistochemistry
IMV
Interim Monitoring Visit
IND
Investigational New Drug 
INR
International Normalized Ratio
IOCBP
Individuals of child-bearing potential
IRB
Institutional Review Board
IV
Intravenous
LDH 
Lactate dehydrogenase
LP
Laboratory of Pathology
LVSI
Lymphovascular space invasion
MCV
Mean corpuscular volume
MMR
Mismatch repair
MOP
Manual of Operational Procedures
MRI
Magnetic Resonance Imaging
MSI-H
Microsatellite instability high
NCCN
National Comprehensive Cancer Network
NCI
National Cancer Institute
NCT
National Clinical Trial (number)
NIH
National Institutes of Health

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Abbreviation
Term
NK
Neurokinin 1
NSMP
Non-specific molecular profile
OHSRP
Office for Human Subjects Research Protections
OPR
Office of Patient Recruitment
ORR
Objective Response Rate
OS
Overall survival
OSRO
Office of Sponsor and Regulatory Oversight
PARPi
Poly-ADP-Ribose Polymerase inhibitor
PBMC
Peripheral blood mononuclear cell
PD
Progressive Disease
PD-1
Programmed cell death protein 1
PD-L1
Programmed death-ligand 1
PDTS
Protocol Deviation Tracking System
PET
Positron Emission Tomography
PFS
Progression-free survival
PI
Principal Investigator
PO
Per Os
POLEmut
Polymerase ε ultramutated
PR
Partial Response
PRBC
Packed red blood cell
PT
Prothrombin time
QA
Quality Assurance
QC
Quality Control
RBC
Red blood cell
RDW
Red cell distribution width
RECIST
Response Evaluation Criteria in Solid Tumors
RNA
Ribonucleic acid
RR
Response rate
SAE
Serious Adverse Event/Serious Adverse Experience
SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2
SAV
Site Assessment Visit
SC
Subcutaneous
SCC
Squamous cell carcinoma
SD
Stable disease
SEC
Serous endometrial cancer
SG
Sacituzumab govitecan
SGO
Society of Gynecologic Oncology
SIV
Site Initiation Visit
SNP
Single nucleotide polymorphisms
SOP
Standard Operating Procedure
SROS
Sponsor Regulatory Oversight Support
TNBC
Triple negative breast cancer

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Abbreviation
Term
TOP1
Topoisomerase 1
TOP1i
Topoisomerase 1 inhibitor
TRAE
Treatment-related adverse events
TROP2
Trophoblastic cell surface antigen 2
TSH
Thyroid Stimulating Hormone
UGT1A1
Uridine diphosphate-glucuronosyltransferase 1A1
ULN
Upper limit of normal
US
United States
VEGF
Vascular endothelial growth factor
VL
Viral load
WBC
White blood cells
WMB
Women’s Malignancies Branch

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16 APPENDICES
16.1 APPENDIX A: PERFORMANCE STATUS CRITERIA
ECOG Performance Status Scale
Grade
Descriptions
0
Normal activity. Fully active, able to carry on all pre-disease 
performance without restriction.
1
Symptoms, but ambulatory. Restricted in physically strenuous 
activity, but ambulatory and able to carry out work of a light or 
sedentary nature (e.g., light housework, office work).
2
In bed <50% of the time. Ambulatory and capable of all self-
care, but unable to carry out any work activities. Up and about 
more than 50% of waking hours.
3
In bed >50% of the time. Capable of only limited self-care, 
confined to bed or chair more than 50% of waking hours.
4
100% bedridden. Completely disabled. Cannot carry on any self-
care. Totally confined to bed or chair.
5
Dead.

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16.2 APPENDIX B: ANAPHYLAXIS PRECAUTIONS
16.2.1 Equipment needed
•
Monitoring devices: EKG monitor, blood pressure monitor, oxygen saturation monitor, and 
thermometer
•
Oxygen
•
Epinephrine for intravenous, intramuscular, and endotracheal administration in accordance 
with institutional guidelines
•
Antihistamines
•
Corticosteroids
•
Intravenous infusion solutions, tubing, catheters, and tape
16.2.2 Procedures
In the event of a suspected anaphylactic reaction during study treatment infusion, the following 
procedures should be performed:
1. Stop the study treatment infusion.
2. Call for additional medical assistance.
3. Maintain an adequate airway.
4. Ensure that appropriate monitoring is in place, with continuous EKG and pulse oximetry 
monitoring, if possible.
5. Administer antihistamines, epinephrine, or other medications as required by participant 
status and as directed by the physician in charge.
6. Continue to observe the participant and document observations.
7. Draw serum/plasma samples for immunogenicity testing.
8.
Ask participant to return for washout immunogenicity sample if appropriate.