Two Part (Phase1b/ Phase3) Trial of Subcutaneous Dostarlimab Plus Carboplatin-Paclitaxel in Participants With Primary Advanced or Recurrent Endometrial Cancer (SAPPHIRE)

October 14, 2026 updated by: GlaxoSmithKline

An Open-label, Multicenter, 2-Part Study: A Phase 1b Dose Selection Followed by a Randomized Phase 3 to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Dostarlimab Plus Carboplatin-Paclitaxel Versus Intravenous Dostarlimab Plus Carboplatin-Paclitaxel in Participants With Primary Advanced or Recurrent Endometrial Cancer (SAPPHIRE)

This is an open-label study, meaning both the researchers and participants will know which treatment is being given.

The study has two parts. In Part 1, researchers will identify the most suitable SC dose. In Part 2, participants will be randomly assigned by chance to receive dostarlimab as either an SC injection or an IV infusion. All participants will also receive carboplatin and paclitaxel. Treatment may continue for up to 3 years, with participants closely monitored throughout the study.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

378

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Participant is at least 18 years of age (or the legal age of consent in the jurisdiction in which the trial is taking place) at the time of signing the Informed Consent Form (ICF).
  • Participant has primary Stage III or Stage IV disease or first recurrent EC.
  • Participant must have a documented Mismatch repair (MMR)/Microsatellite Instability (MSI) status.
  • Participant is capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the ICF and in the protocol.
  • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 for Part 1 and an ECOG performance status of 0 or 1 for Part 2.
  • Participant has adequate organ function.

Exclusion Criteria:

  • Participant has history of or active autoimmune disease that has required systemic treatments within the 2 years prior to screening.
  • Participant has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or known hypersensitivity to carboplatin, paclitaxel or dostarlimab components or excipients.
  • Participant has received prior therapy with anti-programmed death protein 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-PD-L2 agent.
  • Participant has known uncontrolled brain or central nervous system (CNS) metastases.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1 (Phase 1b) SC dostarlimab and IV dostarlimab

Participants will receive SC dostarlimab in Cohorts 1, 2, 4, 5 and 6, at different doses, to determine the doses of SC dostarlimab that will yield drug exposures comparable to approved IV dosing regimens. Participants in Cohort 3 will receive IV dostarlimab. Participants in all cohorts will receive carboplatin and paclitaxel. After 6 cycles, all participants will receive IV dostarlimab for up to 3 years until progression, death, or intolerable toxicities.
Biological: Dostarlimab

Dostarlimab will be administered as SC injection and IV infusion

Drug: Carboplatin and paclitaxel

Carboplatin and paclitaxel will be administered as an IV infusion
Experimental: Part 2 (Phase 3): SC dostarlimab (experimental) or IV dostarlimab (standard of care)

Eligible participants will be randomly assigned to receive either SC dostarlimab or IV dostarlimab (standard of care arm) in a 1:1 ratio. Participants randomized to the experimental arm will receive SC dostarlimab in combination with carboplatin and paclitaxel for 6 cycles, followed by SC dostarlimab monotherapy for up to 3 years of treatment in total. Participants randomized to the standard of care arm will receive IV dostarlimab in combination with carboplatin and paclitaxel for 6 cycles, followed by IV dostarlimab monotherapy for up to 3 years of treatment in total.
Biological: Dostarlimab

Dostarlimab will be administered as SC injection and IV infusion

Drug: Carboplatin and paclitaxel

Carboplatin and paclitaxel will be administered as an IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part 1: Serum Trough Concentration (Ctrough) After First Dose of Dostarlimab
Time Frame: Up to 42 days
Up to 42 days
Part 1: Area Under the Concentration-time Curve (AUC) of Dostarlimab
Time Frame: Up to 42 days
Up to 42 days
Part 2: Observed Ctrough of Dostarlimab
Time Frame: Up to 168 days
Up to 168 days
Part 2: Model-predicted (MP) AUC of Dostarlimab
Time Frame: Up to 21 days
Up to 21 days
Part 2: MP AUC of Dostarlimab
Time Frame: Up to 168 days
Up to 168 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Ctrough of Dostarlimab
Time Frame: Up to 42 days
Up to 42 days
Part 1: AUC of Dostarlimab
Time Frame: Up to 42 days
Up to 42 days
Part 1: Maximum Observed Concentration (Cmax) of Dostarlimab
Time Frame: Up to 42 days
Up to 42 days
Part 1: Time to Peak Drug Concentration (Tmax) of Dostarlimab
Time Frame: Up to 42 days
Up to 42 days
Parts 1 and 2: Number of Participants Experiencing Adverse Events (AEs), Serious AEs (SAEs), Treatment-emergent AEs (TEAEs) and Immune-mediated AEs (imAEs)
Time Frame: Up to 39 months
Up to 39 months
Parts 1 and 2: Number of Participants with TEAEs Leading to Infusion or Injection Interruption, Dose Modifications, Trial Intervention Discontinuation, or Death
Time Frame: Up to 39 months
Up to 39 months
Parts 1 and 2: Confirmed Overall Response Rate (ORR)
Time Frame: Up to 3 years

Confirmed ORR is defined as the percentage of participants reaching confirmed complete response (CR) or confirmed partial response (PR) per RECIST 1.1 by blinded independent central review (BICR) and investigator assessment
Up to 3 years
Parts 1 and 2: Duration of Response (DoR)
Time Frame: Up to 3 years

DoR per RECIST 1.1 by BICR and investigator assessment is defined as the time from the date of first documented objective response of CR or PR that is subsequently confirmed until the date of first documented progressive disease (PD) or death due to any cause, whichever comes first
Up to 3 years
Parts 1 and 2: Progression-free Survival (PFS)
Time Frame: Up to 3 years

PFS is defined as the time from the date of randomization to the date of first documented objective tumor progression per RECIST 1.1 by BICR and investigator assessment or death due to any cause, whichever comes first
Up to 3 years
Parts 1 and 2: Overall Survival (OS)
Time Frame: Up to 3 years

OS is defined as the time from the date of randomization to the date of death due to any cause
Up to 3 years
Part 1: Number of Participants with Antidrug Antibody (ADAs) against Dostarlimab
Time Frame: Up to 39 months
Up to 39 months
Part 2: Number of Participants with ADAs against Dostarlimab
Time Frame: Up to 3 years
Up to 3 years
Part 2: MP Ctrough of Dostarlimab
Time Frame: Up to 168 days
Up to 168 days
Part 2: MP Ctrough at Steady State of Dostarlimab
Time Frame: Up to 168 days
Up to 168 days
Part 2: MP AUC at Steady State of Dostarlimab
Time Frame: Up to 168 days
Up to 168 days
Part 2: MP Cmax of Dostarlimab
Time Frame: Up to 168 days
Up to 168 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 12, 2026

Primary Completion (Estimated)

November 5, 2030

Study Completion (Estimated)

November 5, 2032

Study Registration Dates

First Submitted

September 30, 2026

First Submitted That Met QC Criteria

September 30, 2026

First Posted (Actual)

October 6, 2026

Study Record Updates

Last Update Posted (Actual)

October 19, 2026

Last Update Submitted That Met QC Criteria

October 14, 2026

Last Verified

October 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 300118
  • 2025 (U.S. NIH Grant/Contract)
  • 2025-525060-15-00 (Ctis)
  • EN-35 (Other Identifier: ENGOT Number)
  • GOG-3125 (Other Identifier: GOG Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf

IPD Sharing Time Frame

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

IPD Sharing Access Criteria

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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