A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer

NCT ID: NCT03981796

Last Updated: 2025-09-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

785 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-18

Study Completion Date

2026-11-26

Brief Summary

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This is a 2 part study. Part 1 is to evaluate the efficacy and safety of dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus placebo plus carboplatin-paclitaxel followed by placebo; and Part 2 is to evaluate the efficacy and safety of dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo in participants with recurrent or primary advanced (Stage III or IV) endometrial cancer.

Detailed Description

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Conditions

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Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The participant, Investigator, study staff, and the Sponsor study team and its representatives will be blinded to the assigned treatment.

Study Groups

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Arm 1: Participants receiving dostarlimab + Carboplatin-paclitaxel followed by dostarlimab

Group Type ACTIVE_COMPARATOR

Dostarlimab

Intervention Type BIOLOGICAL

Participants will be administered dostarlimab

Carboplatin

Intervention Type DRUG

Participants will be administered carboplatin

Paclitaxel

Intervention Type DRUG

Participants will be administered paclitaxel

Arm 2: Participants receiving placebo + carboplatin-paclitaxel followed by placebo

Group Type PLACEBO_COMPARATOR

Placebo matching dostarlimab

Intervention Type DRUG

Participants will be administered placebo matching dostarlimab

Carboplatin

Intervention Type DRUG

Participants will be administered carboplatin

Paclitaxel

Intervention Type DRUG

Participants will be administered paclitaxel

Arm 3: Participants receiving dostarlimab + carboplatin-paclitaxel followed by dostarlimab+niraparib

Group Type ACTIVE_COMPARATOR

Dostarlimab

Intervention Type BIOLOGICAL

Participants will be administered dostarlimab

Carboplatin

Intervention Type DRUG

Participants will be administered carboplatin

Paclitaxel

Intervention Type DRUG

Participants will be administered paclitaxel

Niraparib

Intervention Type DRUG

Participants will be administered niraparib

Arm 4: Participants receiving placebo + carboplatin-paclitaxel followed by placebo

Group Type PLACEBO_COMPARATOR

Placebo matching dostarlimab

Intervention Type DRUG

Participants will be administered placebo matching dostarlimab

Carboplatin

Intervention Type DRUG

Participants will be administered carboplatin

Paclitaxel

Intervention Type DRUG

Participants will be administered paclitaxel

Placebo matching Niraparib

Intervention Type DRUG

Participants will be administered placebo matching Niraparib

Interventions

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Dostarlimab

Participants will be administered dostarlimab

Intervention Type BIOLOGICAL

Placebo matching dostarlimab

Participants will be administered placebo matching dostarlimab

Intervention Type DRUG

Carboplatin

Participants will be administered carboplatin

Intervention Type DRUG

Paclitaxel

Participants will be administered paclitaxel

Intervention Type DRUG

Niraparib

Participants will be administered niraparib

Intervention Type DRUG

Placebo matching Niraparib

Participants will be administered placebo matching Niraparib

Intervention Type DRUG

Other Intervention Names

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TSR-042

Eligibility Criteria

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Inclusion Criteria

Part 1 and Part 2:

* Female participant is at least 18 years of age.
* Participant has histologically or cytologically proven endometrial cancer with recurrent or advanced disease.
* Participant must have primary Stage III or Stage IV disease or first recurrent endometrial cancer with a low potential for cure by radiation therapy or surgery alone or in combination and meet at least one of the following criteria;

1. Participant has primary Stage IIIA to IIIC1 disease with presence of evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v).1.1 based on Investigator's assessment. Lesions that are equivocal or can be representative of post-operative change should be biopsied and confirmed for the presence of tumor;
2. Participant has primary Stage IIIC1 disease with carcinosarcoma, clear cell, serous, or mixed histology (containing greater than or equal to \[\>=\] 10 percent carcinosarcoma, clear cell, or serous histology) regardless of presence of evaluable or measurable disease on imaging;
3. Participant has primary Stage IIIC2 or Stage IV disease regardless of the presence of evaluable or measurable disease;
4. Participant has first recurrent disease and is naïve to systemic anticancer therapy;
5. Participant has received prior neo-adjuvant/adjuvant systemic anticancer therapy and had a recurrence or progression of disease (PD) \>=6 months after completing treatment (first recurrence only).
* Participant has an ECOG performance status of 0 or 1.
* Participant has adequate organ function.

Part 2 only:

* Participants must have normal blood pressure (BP) or adequately treated and controlled hypertension (systolic BP lesser than or equal to \[\<=\] 140 millimeter of mercury \[mmHg\] and diastolic BP \<=90 mmHg).
* Participants must be able to take medication orally, by mouth (PO).

Exclusion Criteria

Part 1 and Part 2:

* Participant has received neo-adjuvant/adjuvant systemic anticancer therapy for primary Stage III or IV disease and:

1. has not had a recurrence or PD prior to first dose on the study OR
2. has had a recurrence or PD within 6 months of completing systemic anticancer therapy treatment prior to first dose on the study.
* Participant has had \>1 recurrence of endometrial cancer.
* Participant has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-ligand 1 (anti-PD-L1), or anti-PD-ligand 2 (anti-PD-L2) agent.
* Participant has received prior anticancer therapy (chemotherapy, targeted therapies, hormonal therapy, radiotherapy, or immunotherapy) within 21 days or \<5 times the half-life of the most recent therapy prior to Study Day 1, whichever is shorter.
* Participant has a concomitant malignancy, or participant has a prior non-endometrial invasive malignancy who has been disease-free for \<3 years or who received any active treatment in the last 3 years for that malignancy. Non-melanoma skin cancer is allowed.
* Participant has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both.
* Participant has not recovered (that is \[i.e.\], to Grade \<=1 or to Baseline) from cytotoxic therapy induced AEs or has received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor \[G-CSF\], granulocyte macrophage colony-stimulating factor \[GM-CSF\], or recombinant erythropoietin) within 21 days prior to the first dose of study drug.
* Participant has not recovered adequately from AEs or complications from any major surgery prior to starting therapy.
* Participant is currently participating and receiving study treatment or has participated in a study of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment.
* Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection requiring systemic therapy.
* Participant has received, or is scheduled to receive, a live vaccine within 30 days before first dose of study treatment, during study treatment, and for up to 180 days after receiving the last dose of study treatment.

Part 2 only:

* Participant has received prior therapy with a poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitor.
* Participant has clinically significant cardiovascular disease.
* Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
* Participant is at increased bleeding risk due to concurrent conditions.
* Participant has participated in Part 1 of this study
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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European Network of Gynaecological Oncological Trial Groups (ENGOT)

OTHER

Sponsor Role collaborator

GOG Foundation

NETWORK

Sponsor Role collaborator

Tesaro, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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Phoenix, Arizona, United States

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Scottsdale, Arizona, United States

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Tucson, Arizona, United States

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Tucson, Arizona, United States

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Newport Beach, California, United States

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Palo Alto, California, United States

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Deerfield Beach, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Savannah, Georgia, United States

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Hinsdale, Illinois, United States

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Zion, Illinois, United States

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Fort Wayne, Indiana, United States

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Indianapolis, Indiana, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Lexington, Kentucky, United States

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Covington, Louisiana, United States

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New Orleans, Louisiana, United States

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Shreveport, Louisiana, United States

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Boston, Massachusetts, United States

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Springfield, Massachusetts, United States

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Detroit, Michigan, United States

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St Louis, Missouri, United States

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Lebanon, New Hampshire, United States

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Albuquerque, New Mexico, United States

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Rio Rancho, New Mexico, United States

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Albany, New York, United States

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Mineola, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Kernersville, North Carolina, United States

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Mount Airy, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Hilliard, Ohio, United States

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Hilliard, Ohio, United States

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Tulsa, Oklahoma, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Willow Grove, Pennsylvania, United States

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Providence, Rhode Island, United States

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Knoxville, Tennessee, United States

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Austin, Texas, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Charlottesville, Virginia, United States

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Roanoke, Virginia, United States

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Seattle, Washington, United States

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Grodno, , Belarus

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Minsk, , Belarus

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Aalst, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Calgary, Alberta, Canada

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Winnipeg, Manitoba, Canada

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Ottawa, Ontario, Canada

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Sault Ste. Marie, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Brno, , Czechia

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Prague, , Czechia

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Aalborg, , Denmark

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Copenhagen, , Denmark

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Herlev, , Denmark

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Odense C, , Denmark

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Roskilde, , Denmark

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Kuopio, , Finland

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Tampere, , Finland

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Turku, , Finland

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Amberg, , Germany

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Bad Homburg, , Germany

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Cologne, , Germany

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Dessau, , Germany

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Dresden, , Germany

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Essen, , Germany

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Essen, , Germany

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Frankfurt, , Germany

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Giessen, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Jena, , Germany

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Karlsruhe, , Germany

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Kiel, , Germany

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Lübeck, , Germany

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Mainz, , Germany

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München, , Germany

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Offenbach, , Germany

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Ravensburg, , Germany

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Rosenheim, , Germany

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Tübingen, , Germany

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Ulm, , Germany

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Wiesbaden, , Germany

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Marousi, , Greece

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Thessaloniki, , Greece

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Budapest, , Hungary

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Debrecen, , Hungary

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Ashkelon, , Israel

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Beersheba, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Rehovot, , Israel

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Tel Aviv, , Israel

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Candiolo, , Italy

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Carpi MO, , Italy

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Lecce, , Italy

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Milan, , Italy

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Naples, , Italy

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Ponderano BI, , Italy

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Rome, , Italy

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Sassuolo, , Italy

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Trento, , Italy

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Udine, , Italy

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Amsterdam, , Netherlands

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Eindhoven, , Netherlands

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Enschede, , Netherlands

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Groningen, , Netherlands

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Maastricht, , Netherlands

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Rotterdam, , Netherlands

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Bergen, , Norway

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Oslo, , Norway

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Stavanger, , Norway

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Troms, , Norway

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Trondheim, , Norway

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Bialystok, , Poland

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Gdynia, , Poland

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Lodz, , Poland

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Olsztyn, , Poland

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Poznan, , Poland

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Szczecin, , Poland

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Warsaw, , Poland

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Barcelona, , Spain

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Barcelona, , Spain

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Donostia / San Sebastian, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Málaga, , Spain

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Murcia, , Spain

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Valencia, , Spain

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Linköping, , Sweden

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Lund, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Adapazarı, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Chernihiv, , Ukraine

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Kharkiv, , Ukraine

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Brighton, , United Kingdom

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Cambridge, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Truro, , United Kingdom

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Countries

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United States Belarus Belgium Canada Czechia Denmark Finland Germany Greece Hungary Israel Italy Netherlands Norway Poland Spain Sweden Turkey (Türkiye) Ukraine United Kingdom

References

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Mansoor R Mirza, Dana M Chase, Brian M Slomovitz, René dePont Christensen, Zoltán Novák, Destin Black, Lucy Gilbert, Sudarshan Sharma, Giorgio Valabrega, Lisa M Landrum, Lars C Hanker, Ashley Stuckey, Ingrid Boere, Michael A Gold, Annika Auranen, Bhavana Pothuri, David Cibula, Carolyn McCourt, Francesco Raspagliesi, Mark S Shahin, Sarah E Gill, Bradley J Monk, Joseph Buscema, Thomas J Herzog, Larry J Copeland, Min Tian, Zangdong He, Shadi Stevens, Eleftherios Zografos, Robert L Coleman, Matthew A Powell, . Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. The New England journal of medicine. 2023-Jun-08;388(23): 2145-2158. DOI : 10.1056/NEJMoa2216334 PMID: 36972026

Reference Type BACKGROUND

Banerjee S, Ingles Russo Garces A, Garside J, Rahman T, Pearson C, Heffernan K. Real-world patient characteristics and survival outcomes in patients with advanced or recurrent endometrial cancer in England: a retrospective, population-based study. BMJ Open. 2024 Nov 24;14(11):e083540. doi: 10.1136/bmjopen-2023-083540.

Reference Type DERIVED
PMID: 39581729 (View on PubMed)

Auranen A, Powell MA, Sukhin V, Landrum LM, Ronzino G, Buscema J, Bauerschlag D, Lalisang R, Bender D, Gilbert L, Armstrong A, Safra T, Nevadunsky N, Sebastianelli A, Slomovitz B, Ring K, Coleman R, Podzielinski I, Stuckey A, Teneriello M, Gill S, Pothuri B, Willmott L, Sharma S, Dabrowski C, Antony G, Stevens S, Mirza MR, Fleming E. Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY). Ther Adv Med Oncol. 2024 Sep 28;16:17588359241277656. doi: 10.1177/17588359241277656. eCollection 2024.

Reference Type DERIVED
PMID: 39346117 (View on PubMed)

Valabrega G, Powell MA, Hietanen S, Miller EM, Novak Z, Holloway R, Denschlag D, Myers T, Thijs AM, Pennington KP, Gilbert L, Fleming E, Zub O, Landrum LM, Ataseven B, Gogoi R, Podzielinski I, Cloven N, Monk BJ, Sharma S, Herzog TJ, Stuckey A, Pothuri B, Secord AA, Chase D, Vincent V, Meyers O, Garside J, Mirza MR, Black D. Patient-reported outcomes in the subpopulation of patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer treated with dostarlimab plus chemotherapy compared with chemotherapy alone in the ENGOT-EN6-NSGO/GOG3031/RUBY trial. Int J Gynecol Cancer. 2025 Jun;35(6):101852. doi: 10.1136/ijgc-2024-005484. Epub 2025 Apr 19.

Reference Type DERIVED
PMID: 39322611 (View on PubMed)

Mirza MR, Chase DM, Slomovitz BM, Christensen RD, Novak Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, Powell MA. A Plain Language Summary of "Dostarlimab for primary advanced or recurrent endometrial cancer". Future Oncol. 2025 Jan;21(2):151-168. doi: 10.2217/fon-2023-0940. Epub 2024 Jul 11.

Reference Type DERIVED
PMID: 38990090 (View on PubMed)

You M, Zeng X, Zhang J, Huang Y, Zhang Y, Cai Z, Hu Y. Cost-effectiveness analysis of dostarlimab plus carboplatin-paclitaxel as first-line treatment for advanced endometrial cancer. Front Immunol. 2023 Sep 4;14:1267322. doi: 10.3389/fimmu.2023.1267322. eCollection 2023.

Reference Type DERIVED
PMID: 37731489 (View on PubMed)

Morton M, Marcu I, Levine M, Cosgrove C, Backes F, O'Malley D, Chambers L. Evaluation of Efficacy and Adverse Events After Second Immunotherapy Exposure in Endometrial and Cervical Carcinoma. Obstet Gynecol. 2023 Aug 1;142(2):360-363. doi: 10.1097/AOG.0000000000005243. Epub 2023 Jul 5.

Reference Type DERIVED
PMID: 37411031 (View on PubMed)

Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novak Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, Powell MA; RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-2158. doi: 10.1056/NEJMoa2216334. Epub 2023 Mar 27.

Reference Type DERIVED
PMID: 36972026 (View on PubMed)

Other Identifiers

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ENGOT-EN6

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-3031

Identifier Type: OTHER

Identifier Source: secondary_id

4010-03-001

Identifier Type: OTHER

Identifier Source: secondary_id

2023-506551-23-00

Identifier Type: CTIS

Identifier Source: secondary_id

213361

Identifier Type: -

Identifier Source: org_study_id

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