A Retrospective, Real-world Multicenter Study of DOstarlimab in Patients With Recurrent or Advanced DNA Mismatch Repair Deficient/Microsatellite Instability-high (dMMR/MSI-H) Endometrial Cancer (DORA Study)
Conditions: Endometrial Cancer
Sponsor: Grupo Español de Investigación en Cáncer de Ovario

Dostarlimab 
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Study Title:  
A retrospective, real-world multicenter study of DOstarlimab in patients with Recurrent or 
Advanced DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) 
endometrial cancer (DORA Study) 
 
 
 
The study will be conducted as described herein and in compliance with Good Clinical Practice 
(GCP), with the Declaration of Helsinki, and with other applicable regulatory requirements 
including but not limited to Institutional Review Board/Ethics Committee (IRB/EC) approval. 
Confidentiality Statement 
All information contained in this document is privileged and confidential. Any 
distribution, copying, or disclosure is strictly prohibited without prior written approval by 
the Sponsor. 
Sponsor:  
Grupo Español de Investigación en Cáncer de 
Ovario (GEICO) 
Principal Investigators: 
Dr. Alejandro Gallego Martínez (Clinical study) 
Dr. Marta Mendiola Sabio (Translational 
study) 
 
Sponsor Study Number: 
GEICO 120-R & GEICO 120-T 
Study Drug Name: 
Dostarlimab 
Clinical Phase:  
Retrospective observational study 
Number of Subjects: 
Around 100-110 
Date of Original Study: 
13 June 2022 
Date of Current Study: 
13 June 2022 
Version:  
1.0 

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LIST OF STUDY CONTACTS 
 
Sponsor 
Grupo Español de Investigación en Cáncer de 
Ovario (GEICO) 
Santa Engracia, 151, 5th Floor, Door 2 
28003 Madrid, Spain 
www.geicogroup.com  
 
 
 
 
Principal Investigators 
Dr. Alejandro Gallego Martínez 
Medical Oncology Department 
Hospital Universitario La Paz 
Paseo de la Castellana 261  
28046, Madrid, Spain 
 
 
Study CRO 
Sofpromed Investigación Clínica, SLU 
Gran Vía Asima, 20, 3rd Floor, Office 23 
07009 Palma de Mallorca, Spain 
Tel: +34 648 414 261 
Fax: +34 971 570 222 
E-mail: ensayos@sofpromed.com  
 
 
Dr. Marta Mendiola Sabio 
Translational Oncology Laboratory 
Hospital Universitario La Paz 
Paseo de la Castellana 261  
28046, Madrid, Spain 
 
 
 
 
 
 

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SPONSOR SIGNATURE PAGE 
Declaration of Sponsor 
 
Title: A retrospective, real-world multicenter study of DOstarlimab in patients with 
Recurrent or Advanced DNA mismatch repair deficient/microsatellite instability-high 
(dMMR/MSI-H) endometrial cancer (DORA Study) 
 
Date of Original Study: 
13 June 2022 
Date of Current Study: 
13 June 2022 
Version:  
 
 
1.0 
 
This observational plan was subjected to critical review and has been approved by the 
Sponsor. The information contained herein is consistent with the current risk/benefit 
evaluation of the investigational product as well as with the moral, ethical, and scientific 
principles governing clinical research as set out in the Declaration of Helsinki and the 
guidelines on Good Clinical Practice. 
 
 
_____________________________________ 
_____________________ 
Sponsor Signature 
                      Date 
 
 

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INVESTIGATOR SIGNATURE PAGE 
 
Declaration of the Investigator 
 
Title: A retrospective, real-world multicenter study of DOstarlimab in patients with 
Recurrent or Advanced DNA mismatch repair deficient/microsatellite instability-high 
(dMMR/MSI-H) endometrial cancer (DORA Study) 
 
Date of Original Study: 
13 June 2022 
Date of Current Study: 
13 June 2022 
Version:  
 
 
1.0 
 
I have read this study in its entirety, including all appendices.  By signing this study, 
I agree to conduct the study in accordance with the plan described herein, the current 
International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice 
(GCP), and applicable regulatory requirements, following approval by an Independent 
Ethics Committee (IEC)/Institutional Review Board (IRB). I will ensure that all personnel 
involved in the study under my direction will be informed about the contents of this study 
and will receive all instructions necessary to perform the study as described herein. 
 
Investigator 
 
 
_____________________________________ 
_____________________ 
Investigator Signature 
 
 
 
 
Date 
 
 
 
_____________________________________ 
_____________________ 
Investigator Signature 
 
 
 
 
Date 
 
 

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TABLE OF CONTENTS 
LIST OF STUDY CONTACTS .......................................................................... 2 
SPONSOR SIGNATURE PAGE ........................................................................ 3 
INVESTIGATOR SIGNATURE PAGE ............................................................. 4 
TABLE OF CONTENTS .................................................................................... 5 
LIST OF ABBREVIATIONS AND DEFINITIONS .......................................... 9 
1. 
SUMMARY ................................................................................... 11 
1.1. 
Study Design .................................................................................. 11 
1.1.1. 
Primary Clinical Objective ............................................................. 11 
1.1.2. 
Secondary Clinical Objectives ....................................................... 11 
1.1.3. 
Translational Objectives ................................................................. 11 
1.1.4. 
Population ....................................................................................... 11 
1.1.5. 
Treatment Under Observation ........................................................ 12 
1.1.6. 
Operational Milestones................................................................... 12 
2. 
BACKGROUND AND SIGNIFICANCE ..................................... 13 
2.1. 
Introduction to endometrial cancer................................................. 13 
2.2. 
Metastatic endometrial cancer treatment ........................................ 13 
2.3. 
Mismatch repair deficient (dMMR)/microsatellite instability-high 
(MSI-H) endometrial cancer .......................................................... 15 
2.4. 
Background of Dostarlimab ........................................................... 16 
2.4.1. 
Mechanism of Action and Development ........................................ 16 
2.4.2. 
Clinical Experience ........................................................................ 16 
3. 
STUDY RATIONALE ................................................................... 20 
4. 
STUDY DESIGN ........................................................................... 21 
4.1. 
Overview ........................................................................................ 21 
4.2. 
Study Objectives............................................................................. 21 
4.2.1. 
Primary Clinical Objective ............................................................. 21 
4.2.2. 
Secondary Clinical Objectives ....................................................... 21 
4.2.3. 
Translational Objectives ................................................................. 22 
4.3. 
Study Population ............................................................................ 22 
4.4. 
Treatment Under Observation ........................................................ 22 
4.5. 
Participant Selection ....................................................................... 22 
5. 
COLLECTED DATA AND OUTCOME MEASURES ................ 23 

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5.1. 
Demographics ................................................................................. 23 
5.2. 
Medical History .............................................................................. 23 
5.3. 
Endometrial Cancer History ........................................................... 23 
5.4. 
Endometrial Cancer Previous Treatments ...................................... 23 
5.5. 
Baseline (pre-dostarlimab) ............................................................. 23 
5.6. 
Dostarlimab Treatment ................................................................... 23 
5.7. 
Disease progression after dostarlimab ............................................ 23 
5.8. 
Best Response Assessment ............................................................. 23 
5.9. 
Dostarlimab -Related Adverse Events ........................................... 24 
5.10. 
Death .............................................................................................. 24 
5.11. 
Survival Status ................................................................................ 24 
5.12. 
Subsequent Therapies for Endometrial Cancer .............................. 24 
6. 
SAMPLE SIZE ............................................................................... 25 
7. 
STANDARD OF CARE ................................................................ 26 
8. 
DATA COLLECTION PROCESS ................................................ 27 
8.1. 
Patient Information and Consent .................................................... 27 
8.2. 
Clinical Data Entry ......................................................................... 27 
8.3. 
Data Sources ................................................................................... 27 
8.4. 
Limitations of the Research Method .............................................. 28 
9. 
STATISTICAL ANALYSIS .......................................................... 29 
10. 
ADVERSE EVENT REPORTING ................................................ 30 
11. 
BIOLOGICAL SAMPLE COLLECTION AND SHIPMENTS .... 31 
12. 
ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS ........ 32 
12.1. 
Ethics Review ................................................................................. 32 
12.2. 
Ethical Conduct of the Study.......................................................... 32 
12.3. 
Written Informed Consent .............................................................. 32 
13. 
DISCONTINUATION FROM STUDY ........................................ 34 
14. 
DATA HANDLING AND RECORD KEEPING .......................... 35 
14.1. 
Study Approval and Amendments ................................................. 35 
14.2. 
Investigator Responsibilities .......................................................... 35 
14.3. 
Data Collection and Quality Assurance ......................................... 35 
14.4. 
Subject Confidentiality and Data Protection .................................. 35 
14.5. 
Audits and Inspections ................................................................... 36 
14.6. 
Retention of Records ...................................................................... 36 
15. 
PUBLICATION POLICY .............................................................. 37 

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16. 
LIST OF REFERENCES ............................................................... 38 
APPENDIX 1. PERFORMANCE STATUS .................................................. 40 
APPENDIX 2. RADIOLOGICAL RESPONSE CRITERIA ......................... 41 
APPENDIX 3. DOSTARLIMAB EAP INCLUSION/EXCLUSION 
CRITERIA...................................................................................... 42 
 
 
 
 
 

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LIST OF TABLES 
Table 1: List of Abbreviations ............................................................................. 9 
Table 2: Table of Study Milestones ................................................................... 12 
 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS 
Table 1: List of Abbreviations 
Abbreviation 
Definition 
ADR 
Adverse Drug Reaction 
AE 
Adverse event 
AEMPS 
Spanish Agency for Medicinal Products and Medical Devices 
AESI 
Adverse event of special interest 
AUC 
Area under the curve 
CA-125 
Cancer antigen 125 
CBC 
Complete blood count  
CL 
Oral clearance 
CT 
Computed tomography  
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DNA 
Deoxyribonucleic acid 
DOR  
Duration of response  
EAP 
Expanded Access Program 
EC 
Endometrial Cancer 
ECOG 
Eastern Cooperative Oncology Group 
EDMA 
Electronic Data Management System 
EOT 
End of treatment 
FIGO 
International Federation of Gynecology and Obstetrics 
FDA 
Food and Drug Administration 
FFPE 
Formalin-fixed paraffin-embedded  
GCP 
Good clinical practice 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IHC 
Immunohistochemistry  
irAEI 
immune-related adverse events of interest 
IRB 
Institutional review board 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
IgG4 
Immunoglobulin G4  
LLN 
Lower limit of normal 
mAb 
Monoclonal antibody  
MMR 
Mismatch repair system  
dMMR 
Mismatch repair deficient 
pMMR 
Mismatch repair proficient  

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Abbreviation 
Definition 
MSI 
Microsatellite instability 
MSI-H 
High microsatellite instability 
MSI-L 
Low microsatellite instability 
MSS 
Microsatellite stable 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
NGS 
Next generation sequencing 
NSMP 
non-specific molecular profile  
ORR 
Objective response rate 
OS 
Overall survival 
PCR 
Polymerase chain reaction 
PD1 
Programmed cell death-1 
PD-L1/2 
Programmed death-ligand ½ 
PFS 
Progression-free survival 
PK 
Pharmacokinetics 
PIS 
Patient Information Sheet 
POLE 
DNA polymerase epsilon 
PR 
Partial response 
PRO 
Patient reported outcomes 
PS 
Performance status 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious adverse event 
SOC 
Standard of care 
SUSAR 
Suspected unexpected serious adverse reaction 
TCGA 
The Cancer Genome Atlas 
TEAE 
Treatment-emergent adverse events 
ULN 
Upper limit of normal 
 
 

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1. 
SUMMARY 
1.1. 
Study Design 
1.1.1. 
Primary Clinical Objective 
• To assess the antitumor activity of dostarlimab in patients with recurrent or advanced 
mismatch 
repair 
deficient 
(dMMR)/microsatellite 
instability-high 
(MSI-H) 
endometrial cancer, in terms of objective response rate (ORR) and duration of response 
(DOR) based on investigators’ assessment using Response Evaluation Criteria in Solid 
Tumors (RECIST) v1.1. 
1.1.2. 
Secondary Clinical Objectives 
• To assess the effectiveness of dostarlimab in terms of investigator-assessed 
progression-free survival (PFS) and overall survival (OS). 
• To analyze the PFS rate at 6, 12, 18 and 24 months. 
• To assess the disease control rate (DCR) based on investigators’ assessment using 
RECIST 1.1. 
• To evaluate duration of treatment with dostarlimab. 
• To describe the time to response to dostarlimab.  
• To evaluate the safety and tolerability of dostarlimab in patients with dMMR/MSI-H 
endometrial advanced cancer, including immune-related adverse events of interest 
(irAEI). 
• To evaluate Neutrophil-to-lymphocyte ratio as a potential predictive biomarker for 
treatment with dostarlimab.  
1.1.3. 
Translational Objectives 
• To compare centralized immunohistochemistry (IHC) re-testing with local testing. 
• To compare centralized IHC re-testing results with two PCR-based techniques 
(Promega® and Idylla®) and with possible MMR gene alterations (genetic and 
epigenetic). 
• To analyze the overall response rate and progression-free survival of the dMMR/MSI 
population selected by each biomarker technique: IHC, Polymerase chain reaction 
(PCR) Promega®, PCR Idylla®, or gene alteration (next generation sequencing 
(NGS)/hypermetilation).  
1.1.4. 
Population 
The study population consists of adult female patients with diagnosis of dMMR/MSI-H 
recurrent or advanced endometrial cancer with progression to a previous platinum regimen, 
who were treated within the Spanish dostarlimab Expanded Access Program (EAP). 
 

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1.1.5. 
Treatment Under Observation 
In this study, the treatment under observation is dostarlimab administered on day 1 of each 
treatment cycle until disease progression, unacceptable toxicity or patient/doctor’s decision. 
The recommended dose for dostarlimab is 4 cycles of 500 mg every 3 weeks followed by 1000 
mg every 6 weeks for all subsequent cycles. 
1.1.6. Operational Milestones 
Table 2: Table of Study Milestones 
Number of Patients 
Around 100-110 
Enrollment Rate (patients/month) 
Around 35 
Number of Sites 
50-60 
Country 
Spain 
Study Duration 
3 months (recruitment) 
FPI (date) 
December 2022 
LPLV (date) 
March 2023 
Publications and/or Other Reports 
September 2023 (Clinical Study) 
September 2024 (Translational 
Study) 
 

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2. 
BACKGROUND AND SIGNIFICANCE  
2.1. 
Introduction to endometrial cancer 
In Europe, endometrial cancer (EC) is the most common gynecological tumor and the fourth 
among cancer in women (1). There has been an increase in recent years in the incidence of EC, 
likely associated with the aging of the population and the increase in obesity. The incidence of 
EC may continue growing in the following decades (2). In 2018, an estimated 382,069 new 
cases and 89,929 deaths were attributed to this cancer type worldwide (3). Mortality from EC 
has not been modified in recent years, in large part driven by high grade carcinomas that are 
more likely to present at an advanced stage and to ultimately recur.  
EC are classified into various histological subtypes, which differ in frequency, clinical 
presentation, prognosis and associated risk factors. Most ECs are adenocarcinomas, and the 
most common of these is the endometrioid subtype (75% to 80% of diagnosed cases). The 
majority of patients are diagnosed with early-stage disease (Stage I or II) and have favorable 
outcomes (5-year overall survival of approximately 75-90%), whereas advanced stages and 
non-endometrioid histologies, such as serous, clear cell, undifferentiated and carcinosarcoma, 
in any stage, are known to be associated with a worse prognosis.  
 
2.2. 
Metastatic endometrial cancer treatment  
For distant dissemination of EC that is not susceptible to radical treatment, systemic therapy 
should be considered. However, patients who recur or present with more advanced disease 
have a low probability of response rates to conventional treatment and clinical outcomes are 
poor.  
For most patients with metastatic EC chemotherapy will be the preferred treatment, with the 
combination of carboplatin and paclitaxel as the standard first-line regimen. The phase III 
GOG 209 trial demonstrated that this regimen was not inferior to the TAP scheme (paclitaxel, 
adriamycin, and cisplatin) in terms of efficacy and had a more favorable toxicity profile. The 
median PFS and overall survival (OS) with carboplatin and paclitaxel were 13 and 37 months, 
respectively (4). There have not been randomized clinical trials comparing chemotherapy with 
hormone therapy as first-line treatments. 
There is no chemotherapy regimen approved in second line. Only limited data are available for 
some drugs derived from small single-arm studies, showing a poor clinical activity, with 
objective response rates (ORRs) of approximately 7% to 14%, and median overall survival 
(OS) of 6 to 11 month. Even for the agents with a higher ORR (13.5%), the reported median 
OS remained at <1 year (Table 1) (5).  
 
 

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Table 1. Summary of efficacy data of different drugs assessed after prior platinum-
containing regimen in endometrial cancer 
 
Agent 
Endpoint 
Summary of Results 
Reference 
Liposomal 
doxorubicin  
ORR 
N=45 
ORR=9.5% 
Median DOR=2.7 months 
Median OS=9.2 months  
GOG 129-H  
Oxaliplatin  
ORR 
N=52 
ORR=13.5%  
Median DOR=10 months (range: 4.1 to 50.3 months)  
GOG 129-K  
Docetaxel  
ORR 
N=26 
ORR=7.7% 
Median OS=6.4 months  
GOG 129-N 
Topotecan  
ORR 
N=28 
ORR=9% 
 Median DOR=4.5 months (N=2 responses) Median 
OS=N/A  
GOG 129-J 
Bevacizumab  
ORR 
N=52 
ORR=13.5% 
Median DOR=6 months  
Median OS=10.6 months  
GOG 229-E  
DOR=duration of response; N=number of patients; N/A=not applicable; NR=not reached; ORR=objective 
response rate; OS=overall survival. Of note: none of these therapies are approved for treatment of endometrial 
cancer.  
 
In addition to chemotherapy, some patients with EC may benefit from hormone therapy, 
mainly those with low-grade tumors and positive hormone receptors. Various hormonal drugs 
(progestins, selective estrogen receptor modulators, gonadotropin-releasing hormone analogs, 
and aromatase inhibitors) have been evaluated in phase II and retrospective studies, 
demonstrating modest activity, with a highly variable ORR (5%–56%) and short PFS (median 
2–9 months) (6,7). A recent randomized phase II trial showed that the ORR and PFS associated 
with letrozole were significantly increased with the addition of palbociclib (8). Hormone 
therapy can be used in the second- line setting, but also in highly selected patients in the first-

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line setting (those with low-grade EC with positive hormone receptors, low tumor burden, and 
slow growth). 
 
2.3. Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) 
endometrial cancer  
EC classification has changed from the Tumor Cancer Genome Atlas (TCGA) and ProMisE 
studies, resulting in a molecular classiﬁcation with prognosis and therapeutic implications 
(9,10). Four subtypes were defined with the following molecular features: mutations in DNA 
polymerase epsilon (POLE), (representing 9-10% of total); MMRd (20-30%); p53 wild-type 
or non-specific molecular profile (NSMP) (43-50%); and p53 abnormal (12-27%).  
dMMR defects can occur somatically or germline due to mutations or hypermethylation of 
their promoters. There are two commonly accepted approaches for the identification of dMMR. 
The first one is based on the expression of MLH1, PMS2, MSH2 and MSH6 proteins by IHC. 
Conserved expression or loss of one or more proteins classify patients in MMR proficient 
(pMMR) and dMMR. The other approach is based on PCR amplification of repetitive regions 
known as microsatellites within the genome. Amplified microsatellite loci by PCR establish 
high microsatellite instability (MSI-H) when two or more markers show instability, low MSI 
(MSI-L) when only one marker is altered, or stable, when none of the markers show instability 
(microsatellite stable, MSS). Different microsatellite panels have been developed. Promega® 
1.2 is a commercial kit based in the Bethesda panel (5 markers commonly studied), but there 
are other commercially available based on the expression of different markers, as the Idylla® 
MSI system analyzed the expression of 7 markers. There are other approaches based on 
discrete panel by PCR, but also commercial solutions based on NGS. 
Tumors with dMMR/MSI-H are associated to a high tumor mutational load, to a large number 
of neoantigens and to tumor-infiltrating lymphocytes, characteristics that confer a higher 
probability to respond to immune checkpoint inhibitors.  
In the last 5 years, immunotherapy is undergoing an important development in EC. The first 
evidence of clinical activity of an immunotherapy in EC was obtained in a phase II trial 
published in 2015. The efficacy of the anti-programmed cell death 1 (anti-PD-1) monoclonal 
antibody pembrolizumab was studied in three cohorts of patients with metastatic solid tumors: 
dMMR colorectal cancer, pMMR colorectal cancer, and dMMR non-colorectal cancer. The 
ORR and progression-free survival (PFS) at 20 weeks for the dMMR non-colorectal cancer 
cohort (which included 2 EC patients) was 71% and 67%, respectively (11). These results 
confirmed the role of MMR status as a predictive biomarker to immunotherapy, and 
pembrolizumab was the first treatment approved by United States Food and Drug 
Administration (FDA) for dMMR tumors that had progressed to a previous line of treatment, 
regardless of the type of neoplasm. Other anti-PD-1 and anti-PD-L1 antibodies, like avelumab 

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or durvalumab, have achieved ORR ranging from 27% to 58% in highly pretreated patients 
with dMMR EC (12,13). 
 
2.4. Background of Dostarlimab 
2.4.1. 
Mechanism of Action and Development 
Dostarlimab (formerly referred to as TSR-042) is a humanized immunoglobulin G4 (IgG4) 
monoclonal antibody (mAb) that binds with high affinity and specificity to the immune 
checkpoint receptor, programmed cell death-1 (PD-1). PD-1 is expressed on the surface of 
activated T-cells, forming part of a complex system of receptors and ligands that are involved 
in controlling T-cell activation. Binding of PD-1 to its ligands (PD-L1, PD-L2) reduces T-cell 
activity in the peripheral tissues during an inflammatory response, limiting lytic ability (14,15). 
PD-L1 and PD-L2 are commonly upregulated on many tumor types in response to multiple 
proinflammatory molecules. Their binding to PD-1 on T-cells contributes to T-cell exhaustion, 
protecting tumor cells from immunologic surveillance and promoting immune suppression; 
blockade of this pathway with a PD-1 inhibitor can therefore enhance anti-tumor effector 
function, resulting in decreased tumor growth (16,17). 
Dostarlimab was generated using a proprietary platform that employs affinity maturation to 
select highly specific antibodies with desired functional characteristics. The functional 
antagonist activity of dostarlimab was confirmed in a mixed lymphocyte reaction assay, 
demonstrating enhanced Interleukin-2 (IL-2) production upon the addition of dostarlimab. 
Dostarlimab has an acceptable safety profile based on toxicology studies in monkeys and in 
nonclinical experiments. Based on published clinical experience with antibodies of the same 
drug class and the nonclinical data for dostarlimab, the safety and activity profile of 
dostarlimab is in line with the expectations for this class of agent. 
 
2.4.2. Clinical Experience  
The efficacy and safety of dostarlimab were investigated in GARNET (Study 4010-01-001), a 
multicenter, non-randomized, multiple parallel cohort, open label study conducted in patients 
with advanced solid tumors.  
The recruitment began in March 2016 and the trial was conducted in 2 parts. Part 1 was a dose–
escalation study to evaluate weight-based doses of dostarlimab. Part 2A evaluated the safety 
of non weight-based fixed doses of dostarlimab, while part 2B enrolled patients into several 
expansion cohorts based on tumor type and MMR status (regarding EC, cohort A1 included 
patients with dMMR tumors, and cohort A2 included patients with pMMR tumors) to assess 
the antitumor activity and safety of dostarlimab. 
Part 1 employed a modified 3 + 3 design to evaluate ascending weight-based doses of 
intravenous infusion. Part 2A assessed the safety and tolerability of two fixed doses of 

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dostarlimab. No dose-limiting toxicities were observed, and the recommended therapeutic dose 
was deter- mined to be 500 mg every 3 weeks for the first 4 cycles followed by 1000 mg every 
6 weeks for all subsequent cycles, based on the efficacy, safety, receptor occupancy (fully 
occupied at all dose levels), and pharmacokinetics analysis. This dosing schedule was selected 
for part 2B. 
In expansion A1 cohort of part 2B eligible patients had recurrent or advanced dMMR/MSI-H 
EC, with measurable disease that had progressed after a platinum-containing chemotherapy 
regimen (administered in the adjuvant setting or for the advanced disease) and were to have 
received no more than 2 lines of therapy for advanced or recurrent disease. The primary 
objective of the A1 cohort analysis was to evaluate the antitumor activity of dostarlimab by 
assessing the ORR by blinded independent central review (BICR) using RECIST v1.1, and 
DOR. 
The secondary endpoints included the following: 1) DCR, defined as the proportion of patients 
with an objective response or stable disease lasting 12 weeks or longer, based on BICR using 
RECIST 1.1 criteria; 2) immune- related ORR (irORR) and immune-related DOR (irDOR) 
based on the investigator assessment using immune-related RECIST (irRECIST); 3) PFS, 
based on BICR using RECIST 1.1; 4) immune- related PFS, based on the investigator 
assessment using irRECIST; and 5) OS. 
A total of 104 patients with MMRd EC were enrolled and treated with dostarlimab. The first 
interim efficacy analysis (data cut-off: July 2019) was performed on only 71 patients who had 
at least 1 measurable lesion and a minimum follow-up of 6 months. Baseline characteristics of 
these patients were: median age 64 years and Eastern Cooperative Oncology Group (ECOG) 
PS 0 (35%) or 1 (65%). A total of 65.3% were FIGO (International Federation of Gynecology 
and Obstetrics) Stage IV at the most recent assessment, and 69.7% had a histologic diagnosis 
of endometrioid carcinoma Type 1. The most common disease grade at diagnosis was Grade 2 
(40.3%). Only half of the patients had received prior treatment for metastatic disease, and the 
median PFS from the last platinum regimen was 6.4 months (range, 1.6–79.6). 
With a median follow-up of 11.2 months, 30 patients achieved an objective response (ORR 
42.3%; 95% CI 30.6%– 54.6%): 9 patients (12.7%) had a complete response, and 21 (29.6%) 
had a partial response. All patients with a confirmed complete response remained in response 
as of the data cutoff date. The ORR was observed independently of histologic subtype and 
previous lines of therapy, although the subgroup analyses were not powered and should be 
interpreted with caution. Although the median DOR was not reached, it was estimated that 
96.4% of the patients would have a sustained response at 6 months and 76.8% at 12 months. 
The DCR was 57.7% (95% CI 45.4%–69.4%), and the median PFS was 8.1 months (95% CI 
3.0–18.0). The median OS was also not reached, with an estimated 76.9% of patients alive at 
12 months (18). 

Dostarlimab 
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The second interim analysis (data cut off: March 2020), with a median follow-up of 16.3 
months, was performed on 103 patients, showing an ORR of 44.7% (95% CI 34.9%–54.8%) 
and a DCR of 57.3% (95% CI 47.2%–67%). 89.1% of patients had a response ongoing, and 
the median DOR was not reached yet. The estimated probabilities of remaining in response at 
6, 12 and 18 months were 97.8%, 90.6%, and 79.2%, respectively (19). 
A subanalysis by the number of prior lines of this cohort has been presented. Patients with only 
1 prior line (n = 66) achieved an ORR of 50% (95% CI 37.4–62.6), while patients with 2 or 
more prior lines (n = 39) achieved an ORR of 35.9% (95% CI 21.2–52.8). 70% of the patients 
with 1 prior line and 67% of the patients with 2 or more prior lines remained in response at the 
data cutoff date (19). 
At 2022 American Society of Clinical Oncology (ASCO) meeting the latest update from the 
third prespecified interim analysis was presented (Data cutoff date: November 1, 2021). A total 
of 151 patients (143 in the efficacy-evaluable population) with dMMR EC were enrolled and 
treated with dostarlimab in A1 cohort.  
With a median follow-up of 27.6 months, 45.5% of patients achieved an objective response 
(95% CI 37.1%– 54.0%): 16.1% had a complete response and 29.4% had a partial response. 
83.1% had an ongoing response at the data cut-off. Although the median DOR was not reached, 
it was estimated that 96.8% of the patients would have a sustained response at 6 months, 93.3% 
at 12 months and 83.7% at 24 months.  The DCR was 60.1% (95% CI 51.6%–68.2%) and the 
median PFS was 6.0 months (95% CI 4.1–18.0). The estimated PFS was 46.4% at 12 months 
and 40.1% at 24 months. The median OS was also not reached, with an estimated 73.3% of 
patients alive at 12 months and 60.5% at 24 months (20).  
Description of selected adverse reactions  
Of the 104 patients included in the safety analysis of the A1 cohort, 65.4% had a treatment-
related adverse event (TRAE), most of which were mild (grade 1 or 2). The most frequent 
TRAEs were asthenia, diarrhea, fatigue, and nausea. The incidence of grade 3–4 TRAEs was 
11.5%; 10 patients (9.6%) experienced at least 1 grade 3–4 TRAE, with colitis the most 
frequent event (2 [1.9%]). Only two patients (1.9%) had to discontinue the study because of a 
TRAE (transaminase increase). Immune-related TRAEs were reported in 23.1% of the 
patients, with diarrhea (5.8%) and hypothyroidism (5.8%) the most frequent; only 6.7% of 
these TRAEs were grade 3–4. No deaths due to treatment-related AEs were reported (18). 
Data on patient-reported outcomes were available for 66 of the 104 patients who were 
administered 1 or more doses of dostarlimab. These outcomes showed that dostarlimab was, 
generally, well tolerated, and key disease-related symptoms, such as pain and fatigue, 
improved while on the treatment. Several AEs, such as nausea, vomiting, constipation, and 
diarrhea, remained relatively stable compared with baseline over the course of the treatment. 

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At the latest interim analysis presented at ASCO 2022 meeting, 17.6% of patients had TRAE 
grade 3 or higher and in 8.5% led to discontinue the treatment.  
The toxicity reported for cohort F of the GARNET trial was similar to the dMMR EC cohort. 
68.8% of the patients experienced a TRAE, and 8.3% experienced at least 1 grade 3 or higher 
TRAE. Only two patients (1.8%) discontinued dostarlimab due to a TRAE, and no deaths were 
attributed to the drug (21). 
 
 

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3. 
STUDY RATIONALE 
There is a paucity of real-world data of patients with EC treated with dostarlimab, something 
that has an especial interest considering the limited evidence available with dostarlimab (only 
a phase I open-label study).  
Moreover, there are only some discrete published studies comparing different dMMR/MSI-H 
approaches in EC and there are almost not data assessing their correlation to ORR of 
immunotherapy. To our knowledge only one phase II trial with avelumab made a comparison 
of dMMR/MSI-H tested by IHC, PCR or NGS, but only 15 patients were assessed in the 
dMMR cohort.   
In January 2021, GlaxoSmithKline opened an EAP in Spain to make dostarlimab available to 
eligible women with recurrent or advanced dMMR/MSI-H endometrial cancer, a clear unmet 
medical need for these endometrial cancer patients.  
EAPs allow patients with a serious or life-threatening disease or condition who are not 
otherwise eligible to participate in a clinical trial and have no other comparable or satisfactory 
therapeutic options to access drugs, with demonstrated benefit in clinical trials, that are pending 
approval. 
This study seeks to evaluate the efficacy and tolerability of dostarlimab in recurrent or 
advanced dMMR/MSI-H endometrial cancer patients treated in a real world setting within the 
Spanish EAP. In addition, the translational study aims to assess the efficacy according to the 
biomarker technique used (IHC, PCR Promega®, PCR Idylla®, or gene alteration by 
NGS/hypermetilation). 
 
 

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4. 
STUDY DESIGN 
4.1. Overview  
This is a multicenter, retrospective, observational (non-interventional) study, in patients treated 
in a real-world setting within the Spanish dostarlimab EAP. The study is planned to be 
conducted in the Medical Oncology departments at 50-60 Spanish GEICO-associated 
hospitals. Its multicenter nature aims to improve the representativeness of the study population 
in Spain. The study would include approximately 110 patients with dMMR/MSI-H recurrent 
or advanced EC, that have progressed on or following prior treatment with a platinum-
containing regimen, treated within the dostarlimab EAP, available in Spain from January 2021 
to September 2022. The total number of participating centers and patients will be confirmed 
once the EAP is closed. 
Patient’s medical records will be screened by local clinical staff to assess for eligibility 
according to selection criteria. The study comprises a single study visit, in which the patient 
will give her informed consent to participate (when the patient is alive) and the physician will 
extract the study data from the patient’s medical charts. 
Alive patients who fulfill inclusion criteria and meet no exclusion criteria will be informed by 
a member of their care team about the purpose of the study, as well as about potential risks and 
benefits of study participation. The written informed consent form (ICF) should be signed prior 
to study initiation in alive patients in order to access their medical records. Deceased patients 
will be still included but their relatives will not be contacted. In these instances, data will be 
collected by members of the direct care team, unless there is a prior express order from the 
patient to preserve confidentiality. All eligible deceased and consenting living patients at the 
participating centers will be included. Data will be directly retrieved from hospital medical 
records and reported in the electronic Case Report Form (eCRF). 
 
4.2. Study Objectives  
4.2.1. Primary Clinical Objective 
 
• To assess the antitumor activity of dostarlimab in patients with recurrent or advanced 
mismatch 
repair 
deficient 
(dMMR)/microsatellite 
instability-high 
(MSI-H) 
endometrial cancer, in terms of objective response rate (ORR) and duration of response 
(DOR) based on investigators’ assessment using Response Evaluation Criteria in Solid 
Tumors (RECIST) v1.1. 
4.2.2. Secondary Clinical Objectives 
• To assess the effectiveness of dostarlimab in terms of investigator-assessed 
progression-free survival (PFS) and overall survival (OS). 
• To analyze the PFS rate at 6, 12, 18 and 24 months. 

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• To assess the disease control rate (DCR) based on investigators’ assessment using 
RECIST 1.1. 
• To evaluate duration of treatment with dostarlimab. 
• To describe the time to response to dostarlimab.  
• To evaluate the safety and tolerability of dostarlimab in patients with dMMR/MSI-H 
endometrial advanced cancer, including immune-related adverse events of interest 
(irAEI). 
• To evaluate Neutrophil-to-lymphocyte ratio as a potential predictive biomarker for 
treatment with dostarlimab.  
 
4.2.3. Translational Objectives 
• To compare centralized immunohistochemistry (IHC) re-testing with local testing. 
• To compare centralized IHC re-testing results with two PCR-based techniques 
(Promega® and Idylla®) and with possible MMR gene alterations (genetic and 
epigenetic). 
• To analyze the overall response rate and progression-free survival of the dMMR/MSI 
population selected by each biomarker technique: IHC, Polymerase chain reaction 
(PCR) Promega®, PCR Idylla®, or gene alteration (next generation sequencing 
(NGS)/hypermetilation).  
4.3. Study Population 
The study population consists of adult female patients with diagnosis of dMMR/MSI-H 
recurrent or advanced endometrial cancer with recurrent disease to a previous platinum, treated 
within the Spanish dostarlimab EAP. 
 
4.4. 
Treatment Under Observation 
In this study, the treatment under observation is dostarlimab administered on day 1 of each 
treatment cycle until disease progression, unacceptable toxicity or patient/doctor’s decision. 
The recommended dose for dostarlimab is 4 cycles of 500 mg every 3 weeks followed by 1000 
mg every 6 weeks for all subsequent cycles. 
4.5. Participant Selection 
• Patients must meet all the following EAP inclusion criteria and none of the exclusion 
criteria to be eligible.  
• Participants must have received dostarlimab (at least 1 cycle) within the Spanish EAP. 
 
 

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5. 
COLLECTED DATA AND OUTCOME MEASURES 
5.1. Demographics  
• Age (at dostarlimab treatment initiation within EAP) 
5.2. Medical History 
• Non-oncological history 
• Other cancers 
5.3. Endometrial Cancer History 
• Initial diagnosis date 
• Tumor histology (and degree of tumor differentiation for endometrioid subtype) 
• Disease stage 
• Recurrent or initial metastatic disease  
• MMR (IHC / MSI-H / MMR genetic study/ MLH1 hypermetilation) 
5.4. Endometrial Cancer Previous Treatments  
• Previous surgeries 
• Previous drugs (types and number of previous treatments) 
• Previous radiotherapy  
5.5. Baseline (pre-dostarlimab) 
• ECOG 
• Existence of measurable disease 
• CA 125 
5.6. Dostarlimab Treatment 
• Start date (first dose) 
• Number of cycles  
• Last dose  
• Number of interruptions 
• End of treatment date 
• End of treatment reason (toxicity, doctor’s decision, patient’s decision, progression or 
other) 
5.7. Disease progression after dostarlimab 
• Progression date 
• Progression type 
5.8. Best Response Assessment 
• Radiological best overall response 

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• Radiological best overall response assessment date 
• Number of dostarlimab cycles previous to first and best radiological response 
• CA125 best overall response 
• CA125 best overall response assessment date 
5.9. Dostarlimab -Related Adverse Events 
• Event term according to Common Terminology Criteria for Adverse Events (CTCAE) 
criteria 
• Time from dostarlimab initiation 
• Event duration 
• Grade 
• Action taken with dostarlimab 
• Outcome 
5.10. Death 
• Date of death 
• Cause of death 
5.11. Survival Status 
• Last follow-up date 
• Status 
5.12. Subsequent Therapies for Endometrial Cancer 
• Subsequent drugs 

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6. 
SAMPLE SIZE  
The study will include between 100-110 patients in total (retrospective in all cases) recruited 
in 50-60 sites.  
 
The population will include all patients who received dostarlimab at least during one cycle as 
part of the EAP in GEICO-associated hospitals. The sample size will be based on the number 
of patients treated in the EAP of Spain. 
 
There will be no formal calculation of the sample size. Most patients included in the Spanish 
EAP will be analyzed. 
 

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7. 
STANDARD OF CARE  
In this retrospective observational study, patients will not be exposed to clinical interventions 
different from those belonging to the standard of care. There are no study-specific procedures 
other than the normal activities that patients would undergo if they were not participating in 
the study. Accessible/reachable patients will be interviewed during routine care visits and 
principal investigators at each site will offer them the possibility of participating in the study. 
This will involve reading and signing the ICF.  

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8. 
DATA COLLECTION PROCESS 
8.1. Patient Information and Consent 
All patients participating in the study (accessible, alive patients who can be interviewed in the 
hospital) will receive a Patient Information Sheet (PIS) describing, in simple language, the 
goals, scope, procedures and relevant implications of the study. The PIS will integrate an ICF 
to be signed by the patient, which is indispensable for study participation (for accessible 
patients). Written informed consent must be given by each accessible/reachable patient before 
study initiation (prior to registration of the patient in the eCRF). The PIS/ICF will include the 
consent of patients for the collection and analysis of their clinical data. 
Data of inaccessible/unreachable patients (dead, lost, etc.) could still be used according to the 
permissions of ethics committees and Spanish law, regarding the use of data in retrospective 
studies. 
 
8.2. Clinical Data Entry 
Participating local sites (GEICO-associated hospitals with expertise in gynecological cancer 
management) will enter clinical data of patients in the study eCRF in order to create a 
multicenter database. The specific data items to be entered in the eCRF are described in an 
eCRF specification provided as a separate document. 
It is expected that data collection for the study will take place on an ongoing basis since the 
first site is activated and until around 100-110 subjects have been accrued, depending on 
timelines of regulatory and committees’ authorizations.  
Considering the retrospective nature of the study, no data will be recorded prospectively. For 
alive patients, no data generated after the date of ICF signature will be collected.  
 
8.3. Data Sources 
Considering the retrospective nature of this study, the source of information will be the 
patient´s medical chart. Other potential sources of data are pharmacy records, databases or 
electronic prescribing systems. The data to be extracted in this study which are available in the 
patient´s medical charts will be recorded in the eCRFs. Only data obtained before study 
initiation (the date of the first ethics committee approval) will be extracted from the patient´s 
medical chart in order to ensure they are retrospective in nature. Data unavailable in patients’ 
medical charts will be mentioned in the eCRFs as “not available”. The degree of detail and 
completeness of data extracted for this study will depend on their availability according to local 
clinical practice. The investigator participating in this study will revise patient´s medical chart 
to confirm eligibility of the patient. Once it is confirmed that all selection criteria are meet and 
informed consent is given, the investigator will proceed to extract the study data available 

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(previously registered) in patient’s medical charts and completing the eCRF. Patient medical 
information obtained by this study is confidential and may only be disclosed to third parties as 
permitted by the informed consent form signed by the subject, unless permitted or required by 
law. Confidentiality standards will be maintained by coding each patient enrolled in this study 
through assignment of a unique subject identification number. 
 
8.4. Limitations of the Research Method 
This is a retrospective study designed to extract information already obtained in an EAP 
clinical practice of the participating sites that is registered in patients´ medical chart. The main 
limitation of this study therefore arises from the obvious limitations of a retrospective chart 
review that uses existing medical data recorded for reasons other than research, including 
incomplete or unrecorded documentation. The validity of study results will therefore be limited 
by the information available and the presence of missing data. 
Nevertheless, it is expected that most data to be collected in this study will be available as they 
are routinely registered in the medical charts of the target population. 
So, the information obtained in this study regarding safety data must be considered with 
caution given that these came from a retrospective review of medical charts where it is likely 
that information on adverse events may has been under recorded in comparison with a 
prospective and controlled clinical trial setting. In addition, safety results must be interpreted 
within the context of the current safety management systems in the participating hospitals. 
 

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9. 
STATISTICAL ANALYSIS 
Statistical analyses and study reports will be developed by the Coordinating Investigator of the 
study in collaboration with the biostatisticians of the study Contract Research Organization 
(CRO). The World Programming System (WPS) platform (a SAS language software) will be 
used for these analyses. 
All variables will be summarized separately. Depending on the type of the variable, the 
following statistics will be reported: 
• Continuous variables: number of subjects (n), number of missings, mean, standard 
deviation (STD), median, standard error (SE, if needed), 25th and 75th percentiles, 
minimum, and maximum.  
• Categorical variables: frequencies and percentages (calculated over the number of non-
missing values).  
In general, minimum and maximum are going to be reported using the same number of decimal 
places as collected in the raw data. Mean, STD, median, 25th and 75th percentiles will be 
reported with one additional decimal place. 
Time to event data will be listed and summarized at every specified timepoint using the number 
patients at risk, number of patients censored, number of patients with the event, Kaplan Meier 
estimate (%), and the 95% confidence interval. In addition, 25th, 50% and 75th percentiles 
from Kaplan-Meier curves will be used. 
Progression-free survival is defined as the time from the date of the first administration of 
dostarlimab and the occurrence of disease progression or death, whichever occurs earlier.  
Overall survival is defined as the time between the start of treatment and death. Patients alive 
at the last follow-up will be censored for the analysis of OS.  
Both PFS and OS will be analyzed using the Kaplan-Meier method. The responses (valid only 
for patients who have started dostarlimab with measurable disease) will be assessed following 
the RECIST 1.1 criteria and reported in percentages. 
Further details on statistical analyses will be specified in the Statistical Analysis Plan (SAP). 
 

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10. 
 ADVERSE EVENT REPORTING 
In non-interventional studies, the sponsor and investigator obligations for the reporting of 
suspected adverse reactions are specified in the Spanish Royal Decree 957/2020, of 3 
November, which contains the guidelines for post-authorization observational studies with 
medicinal products for human use, in accordance with the Guideline on Good 
Pharmacovigilance Practices, Module VIII-Post-Authorization Safety Studies.  
However, considering the retrospective nature of this study, expedited reporting of suspected 
adverse reactions will not be required. All AEs extracted from the data source for the study as 
specified in the protocol will be summarized as part of the final study report publication. 
Reportable events, time for reporting and definitions are included in sections 8.3 and appendix 
14.1 of the EAP (EAP for Dostarlimab in adult patients with recurrent or advanced mismatch 
repair deficient (dMMR)/microsatellite instability-high (MSI-H) endometrial cancer (EC) that 
has progressed on or following prior treatment with a platinum-containing regimen) protocol. 
 

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11. 
BIOLOGICAL SAMPLE COLLECTION AND SHIPMENTS 
Formalin-fixed paraffin-embedded (FFPE) blocks will be sent to the central laboratory, which 
will prepare the biological material according to the analytical needs of the study.  
The central laboratory is: 
Dr. Marta Mendiola 
Laboratorio de Anatomía y Oncología Traslacional 
Edificio IdiPAZ, planta 2 
Paseo de la Castellana 261 
28046 Madrid, Spain 
 
Archival FFPE block (from biopsy/surgery) will be used for: 
1. IHC purposes for the evaluation of expression of MLH1, PMS2, MSH2 and MSH6 proteins 
2. DNA extraction for  
a) microsatellite instability evaluation based on PCR techniques (Promega and Idylla) 
b) Mutation testing (MLH1, PMS2, MSH2 and MSH6 genes) and hypermethlyation 
evaluation (MLH1 gene) 
All tumor and blood samples will be shipped from local sites to the central laboratory via 
courier service coordinated by the study CRO. 
To arrange shipments, please contact: 
Sofpromed Investigación Clínica, SLU 
Tel: +34 648 414 261 
E-mail: ensayos@sofpromed.com 
 
 
 
 

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12. 
ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS 
12.1. Ethics Review 
 
The final study plan, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB or IEC, as appropriate. The Investigator must submit 
written approval to the Sponsor before he or she can enroll any patient into the study. 
The Sponsor (or appointed agent) is responsible for informing the IRB or IEC of any 
amendment to the study plan in accordance with local requirements. The study plan must be 
re-approved by the IRB or IEC upon receipt of amendments and annually, as local regulations 
require. 
The Sponsor (or appointed agent) is also responsible for providing the IRB with reports of any 
reportable serious adverse drug reactions from any other study conducted with the 
investigational product. The Sponsor will provide this information to the Principal 
Investigator. 
Progress reports will be provided to the IRB or IEC according to local regulations and 
guidelines. 
12.2. Ethical Conduct of the Study 
 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with International Conference on Harmonization 
and Good Clinical Practice standards as well as any applicable regulatory requirements.  
This may include an inspection by Sponsor representatives/designees, and/or Regulatory 
Authority representatives at any time. The investigator must agree to the inspection of study-
related records by the Regulatory Authority/Sponsor representatives/designees and must allow 
direct access to source documents to the Regulatory Authority/Sponsor representatives/ 
designees. The investigator must allocate time (investigator and study staff) to discuss findings 
and relevant issues with the regulatory authority/Sponsor representatives. 
Since this is an observational study, it is exempt from the compulsory subscription of 
insurance. 
12.3. Written Informed Consent 
 
The Principal Investigator(s) at each center will ensure that the patient is given full and 
adequate oral and written information about the nature, purpose, possible risk, and benefit of 
the study. Patients must also be notified that they are free to discontinue from the study at any 
time. The patient should be given the opportunity to ask questions and allowed time to consider 
the information provided. 

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The patient’s signed and dated informed consent must be obtained before conducting any study 
procedures. 
The Principal Investigator(s) must maintain the original, signed ICF. A copy of the signed ICF 
must be given to the patient. 

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13. 
DISCONTINUATION FROM STUDY 
All patients included in the study have the right to withdraw from the study at any time by 
withdrawing their consent, without having to give an explanation for this decision and without 
any influence on their clinical follow-up. 

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14. 
DATA HANDLING AND RECORD KEEPING 
14.1. Study Approval and Amendments 
 
The study and all the possible amendments will be approved by Ethics Committee before 
starting any data collection procedure. 
 
14.2. Investigator Responsibilities 
 
Data collection, cleaning, patient’s safety surveillance and compliance to study plan will be 
investigator’s responsibilities. 
 
14.3. Data Collection and Quality Assurance 
 
The Sponsor must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented, including but not limited to the protocol, protocol amendments, 
Informed Consent Forms (if applicable), and documentation of IRB/EC and governmental 
approval (if necessary). The Sponsor shall ensure that the datasets and statistical programs used 
for generating the data included in the final study report are kept in electronic format and are 
available for auditing and inspection. 
 
14.4. Subject Confidentiality and Data Protection 
 
Confidentiality standards should be maintained by coding each patient enrolled in the study 
through assignment of a unique patient identification number so that patient names are not 
included in datasets that are transmitted. The Sponsor undertakes in terms of obtaining, 
processing, preserving, communicating and transferring its data in accordance with the General 
Data Protection Regulation (EU) 2016/679 (GDPR), Spanish Organic Law 3/2018, of 
December 5, on the protection of personal data and guarantee of digital rights. The investigator 
will inform the patients that the data obtained in this study will be stored and analyzed by 
computer according to the international regulations on handling computerized data 
Patient medical information obtained by this study is confidential and may be disclosed to third 
parties only as permitted by the Informed Consent Form (or separate authorization for use and 
disclosure of personal health information) signed by the patient, unless permitted or required 
by law.  
Medical information may be given to a patient’s personal physician or other appropriate 
medical personnel responsible for the patient’s welfare, for treatment purposes.  
 

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Data generated by this study must be available for inspection upon request by representatives 
of national and local health authorities, marketing authorization holder monitors, 
representatives, and collaborators, and the EC for each study site, as appropriate. 
 
14.5. Audits and Inspections 
 
Authorized representatives of the Sponsor, a regulatory authority, an Independent Ethics 
Committee or an Institutional Review Board may visit the site to perform audits or inspections, 
including source data verification. The purpose of a Sponsor audit or inspection is to 
systematically and independently examine all study-related activities and documents to 
determine whether these activities were conducted, and data were recorded, analyzed, and 
accurately reported according to the study plan, Good Clinical Practice (GCP) guidelines of 
the International Conference on Harmonization, and any applicable regulatory requirements. 
The Investigator should contact the Sponsor immediately if contacted by a regulatory agency 
about an inspection. 
 
14.6. Retention of Records 
 
The Principal Investigator must maintain all documentation relating to the study for a minimum 
period of 2 years and for as long as required per regulatory authorities after the last marketing 
application approval or, if not approved, 2 years following the discontinuance of the test article 
for investigation. If it becomes necessary for the Sponsor or the Regulatory Authority to review 
any documentation relating to the study, the Investigator must permit access to such records. 

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15. 
PUBLICATION POLICY 
The final publication of the study results will be written by the coordinating investigators based 
on the final analysis performed. An abstract and a manuscript will be written. 
The draft manuscript will be reviewed by the coordinating investigators, other co-authors and 
representatives from the funding entity. After revision the manuscript will be sent to a major, 
high-impact scientific journal.  
All manuscripts will include an appropriate acknowledgement section, mentioning all 
investigators who have contributed to the study, as well as supporting parties. 
All publications (papers, abstracts, or presentations) including data from the study will be 
submitted for review to all co-authors and the funding entity representatives prior to 
submission.  
In addition, the study may be registered in the clinicaltrials.gov database of the National 
Institute of Health of the United States of America. Provide a plan for publications including 
expected number of publications and timeline. 

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16. 
LIST OF REFERENCES  
1.  
Oaknin A, Bosse TJ, Creutzber CL, Giornelli G, Harter P, Joly F, et al. Endometrial cancer: 
ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up†. Ann Oncol 2022. 
2.  
Morice P, Leary A, Creutzberg C, Abu-Rustum N, Darai E. Endometrial cancer. Lancet 
2016;387(10023):1094–108.  
3.  
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: 
GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 
CA Cancer J Clin. 2018;68(6):394–424.  
4.  
Miller DS, Filiaci VL, Mannel RS, Cohn DE, Matsumoto T, Tewari KS, et al. Carboplatin and 
paclitaxel for advanced endometrial cancer: Final overall survival and adverse event analysis of 
a phase III trial (NRG Oncology/GOG0209). J Clin Oncol. 2020;38(33):3841–50.  
5.  
Connor E V., Rose PG. Management Strategies for Recurrent Endometrial Cancer. Expert Rev 
Anticancer Ther 2018;18(9):873–85.  
6.  
Decruze SB, Green JA. Hormone therapy in advanced and recurrent endometrial cancer: A 
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Mirza MR, Bjørge L, Marmé F, DePont Christensen R, Gil-Martin M, Auranen A, et al. LBA28 
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Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 
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Buchbinder EI, Desai A. CTLA-4 and PD-1 Pathways: Similarities, Differences, and 

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Implications of Their Inhibition. Am J Clin Oncol 2016;39(1).  
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APPENDIX 1. 
PERFORMANCE STATUS 
 
ECOG PS 
KARNOFSKY PS 
0—Fully active, able to carry on all pre-
disease performance without restriction 
100—Normal, no complaints; no evidence 
of disease 
90—Able to carry on normal activity; minor 
signs or symptoms of disease 
1—Restricted in physically strenuous 
activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., 
light house work, office work 
80—Normal activity with effort, some signs 
or symptoms of disease 
70—Cares for self but unable to carry on 
normal activity or to do active work 
2—Ambulatory and capable of all selfcare 
but unable to carry out any work activities; 
up and about more than 50% of waking 
hours 
60—Requires occasional assistance but is 
able to care for most of personal needs 
50—Requires considerable assistance and 
frequent medical care 
3—Capable of only limited selfcare; 
confined to bed or chair more than 50% of 
waking hours 
40—Disabled; requires special care and 
assistance 
30—Severely disabled; hospitalization is 
indicated although death not imminent 
4—Completely disabled; cannot carry on 
any selfcare; totally confined to bed or chair 
20—Very ill; hospitalization and active 
supportive care necessary 
10—Moribund 
5—Dead 
0—Dead 
*Karnofsky D, Burchenal J, The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod 
C, ed. Evaluation of Chemotherapeutic Agents. New York, NY: Columbia University Press; 1949:191–
205. 
**Zubrod C, et al. Appraisal of methods for the study of chemotherapy in man: Comparative 
therapeutic trial of nitrogen mustard and thiophosphoramide. Journal of Chronic Diseases; 1960:11:7-
33. 
 

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APPENDIX 2. 
RADIOLOGICAL RESPONSE CRITERIA 
Response will be assessed by RECIST v.1.1 criteria using investigator's review. 
https://project.eortc.org/recist/wp-content/uploads/sites/4/2015/03/RECISTGuidelines.pdf 
 
 
 

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APPENDIX 3. 
DOSTARLIMAB EAP INCLUSION/EXCLUSION CRITERIA 
 
Inclusion Criteria 
To be considered eligible to participate in this program, all of the following requirements must 
be met: 
1. At least 18 years of age, able to understand the program procedures and agree to 
participate by providing written informed consent. 
2. Histologically diagnosed endometrial cancer (note: all histologies are permitted 
except endometrial sarcoma [including carcinosarcoma]). 
3. Patient has evidence of tumor DNA damage repair dysfunction (dMMR/MSI-H) via 
locally available, validated methodology. 
4. Patient has progressed on or after platinum containing chemotherapy (and has 
received no more than 2 lines of anti-cancer therapy for recurrent or advanced 
(Stage ≥ IIIB) disease (first or second line)); prior treatment with hormone therapies 
is acceptable and does not count towards the number of lines of therapy. 
5. ECOG performance status of ≤ 2. 
6. Adequate organ and bone marrow function, as defined below: 
a. Absolute neutrophil count (ANC) ≥ 1,500/µL 
b. Platelets ≥ 100,000/µL 
c. Hemoglobin ≥ 9 g/dL 
d. Adequate liver and renal function: 
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated 
creatinine clearance ≥ 50 mL/min using Cockcroft-Gault equation for 
patients with creatinine levels > 1.5 × institutional ULN. 
• Total bilirubin ≤ 1.5 × ULN AND direct bilirubin ≤ 1 × ULN. 
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤ 2.5 × ULN unless liver metastases are present, in which case they must 
be ≤ 5 × ULN. 
7. Cannot be satisfactorily treated with available alternative treatments. 
8. Not eligible for a clinical trial with dostarlimab within the indication of the EAP 
(where access to the clinical trial site is possible). 

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9. A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and if one of the following conditions applies: 
• Is a woman of non-childbearing potential (WONCBP) 
OR 
• Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of < 1 % per year), preferably with low user dependency, during 
treatment and for at least 4 months after  treatment. The treating physician 
should evaluate the potential for contraceptive method failure (e.g., 
noncompliance, recently initiated) in relationship to the first dose of dostarlimab. 
A WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours 
before the first dose of dostarlimab. 
The treating physician is responsible for review of medical history, menstrual history, 
and recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
Exclusion Criteria 
Patients will not be eligible for treatment with dostarlimab under this protocol if any of the 
following criteria apply: 
1. Has received prior therapy with an anti-programmed death-1 (anti-PD-1), anti-PD-1- 
ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent. 
2. Is considered a poor medical risk due to a serious, uncontrolled medical disorder, non- 
malignant systemic disease, or active infection requiring antibiotic, antifungal or 
antiviral treatment. 
3. Has undergone major surgery 3 weeks prior to initiating dostarlimab (and not 
recovered from surgical effects). 
4. Has malignancies other than endometrial cancer (except for any other malignancy for 
which the patient is not being actively treated). 
5. Has a history of interstitial lung disease. 
6. Has an active autoimmune disease that required systemic treatment in the past 2 years 
(i.e., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs); 
hormone replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid 
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a 
form of systemic treatment. 

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7. Has experienced ≥ Grade 3 immune related AE with prior immunotherapy, except for 
non-clinically significant laboratory abnormalities. 
8. Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) 
or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected). 
9. Has received a live vaccine within 14 days of 1st dose of dostarlimab. 
10. Has a known hypersensitivity to dostarlimab components or excipients.