Two Part (Phase1b/ Phase3) Trial of Subcutaneous Dostarlimab Plus Carboplatin-Paclitaxel in Participants With Primary Advanced or Recurrent Endometrial Cancer (SAPPHIRE)
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.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 3
Kontakte und Standorte
Studienkontakt
- Name: US GSK Clinical Trials Call Center
- Telefonnummer: 877-379-3718
- E-Mail: GSKClinicalSupportHD@gsk.com
Studieren Sie die Kontaktsicherung
- Name: EU GSK Clinical Trials Call Center
- Telefonnummer: +44 (0) 20 89904466
- E-Mail: GSKClinicalSupportHD@gsk.com
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Sequenzielle Zuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
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. |
Dostarlimab will be administered as SC injection and IV infusion 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. |
Dostarlimab will be administered as SC injection and IV infusion Carboplatin and paclitaxel will be administered as an IV infusion |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Part 1: Serum Trough Concentration (Ctrough) After First Dose of Dostarlimab
Zeitfenster: Up to 42 days
|
Up to 42 days
|
|
Part 1: Area Under the Concentration-time Curve (AUC) of Dostarlimab
Zeitfenster: Up to 42 days
|
Up to 42 days
|
|
Part 2: Observed Ctrough of Dostarlimab
Zeitfenster: Up to 168 days
|
Up to 168 days
|
|
Part 2: Model-predicted (MP) AUC of Dostarlimab
Zeitfenster: Up to 21 days
|
Up to 21 days
|
|
Part 2: MP AUC of Dostarlimab
Zeitfenster: Up to 168 days
|
Up to 168 days
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Part 1: Ctrough of Dostarlimab
Zeitfenster: Up to 42 days
|
Up to 42 days
|
|
|
Part 1: AUC of Dostarlimab
Zeitfenster: Up to 42 days
|
Up to 42 days
|
|
|
Part 1: Maximum Observed Concentration (Cmax) of Dostarlimab
Zeitfenster: Up to 42 days
|
Up to 42 days
|
|
|
Part 1: Time to Peak Drug Concentration (Tmax) of Dostarlimab
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: Up to 39 months
|
Up to 39 months
|
|
|
Parts 1 and 2: Confirmed Overall Response Rate (ORR)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: Up to 39 months
|
Up to 39 months
|
|
|
Part 2: Number of Participants with ADAs against Dostarlimab
Zeitfenster: Up to 3 years
|
Up to 3 years
|
|
|
Part 2: MP Ctrough of Dostarlimab
Zeitfenster: Up to 168 days
|
Up to 168 days
|
|
|
Part 2: MP Ctrough at Steady State of Dostarlimab
Zeitfenster: Up to 168 days
|
Up to 168 days
|
|
|
Part 2: MP AUC at Steady State of Dostarlimab
Zeitfenster: Up to 168 days
|
Up to 168 days
|
|
|
Part 2: MP Cmax of Dostarlimab
Zeitfenster: Up to 168 days
|
Up to 168 days
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Studienleiter: GSK Clinical Trials, GlaxoSmithKline
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Geschätzt)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Urogenitale Erkrankungen
- Genitalerkrankungen
- Urogenitale Neoplasmen
- Neubildungen nach Standort
- Neubildungen
- Weibliche Urogenitalerkrankungen
- Weibliche Urogenitalerkrankungen und Schwangerschaftskomplikationen
- Uteruserkrankungen
- Genitalerkrankungen, weiblich
- Genitale Neubildungen, weiblich
- Uterusneoplasmen
- Endometriale Neubildungen
- Organische Chemikalien
- Kohlenwasserstoffe
- Cycloparaffine
- Kohlenwasserstoffe, alicyclisch
- Kohlenwasserstoffe, zyklisch
- Terpene
- Koordinationskomplexe
- Taxoid
- Cyclodececane
- Diterpene
- Carboplatin
- Paclitaxel
- Dostarlimab
Andere Studien-ID-Nummern
- 300118
- 2025 (US NIH Stipendium/Vertrag)
- 2025-525060-15-00 (Ctis)
- EN-35 (Andere Kennung: ENGOT Number)
- GOG-3125 (Andere Kennung: GOG Number)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
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-Zeitrahmen
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-Zugriffskriterien
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.
Art der unterstützenden IPD-Freigabeinformationen
- STUDIENPROTOKOLL
- SAFT
- ICF
- CSR
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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