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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 3
Contatti e Sedi
Contatto studio
- Nome: US GSK Clinical Trials Call Center
- Numero di telefono: 877-379-3718
- Email: GSKClinicalSupportHD@gsk.com
Backup dei contatti dello studio
- Nome: EU GSK Clinical Trials Call Center
- Numero di telefono: +44 (0) 20 89904466
- Email: GSKClinicalSupportHD@gsk.com
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione sequenziale
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: 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 |
|
Sperimentale: 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 |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
|
Part 1: Serum Trough Concentration (Ctrough) After First Dose of Dostarlimab
Lasso di tempo: Up to 42 days
|
Up to 42 days
|
|
Part 1: Area Under the Concentration-time Curve (AUC) of Dostarlimab
Lasso di tempo: Up to 42 days
|
Up to 42 days
|
|
Part 2: Observed Ctrough of Dostarlimab
Lasso di tempo: Up to 168 days
|
Up to 168 days
|
|
Part 2: Model-predicted (MP) AUC of Dostarlimab
Lasso di tempo: Up to 21 days
|
Up to 21 days
|
|
Part 2: MP AUC of Dostarlimab
Lasso di tempo: Up to 168 days
|
Up to 168 days
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Part 1: Ctrough of Dostarlimab
Lasso di tempo: Up to 42 days
|
Up to 42 days
|
|
|
Part 1: AUC of Dostarlimab
Lasso di tempo: Up to 42 days
|
Up to 42 days
|
|
|
Part 1: Maximum Observed Concentration (Cmax) of Dostarlimab
Lasso di tempo: Up to 42 days
|
Up to 42 days
|
|
|
Part 1: Time to Peak Drug Concentration (Tmax) of Dostarlimab
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: Up to 39 months
|
Up to 39 months
|
|
|
Parts 1 and 2: Confirmed Overall Response Rate (ORR)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: Up to 39 months
|
Up to 39 months
|
|
|
Part 2: Number of Participants with ADAs against Dostarlimab
Lasso di tempo: Up to 3 years
|
Up to 3 years
|
|
|
Part 2: MP Ctrough of Dostarlimab
Lasso di tempo: Up to 168 days
|
Up to 168 days
|
|
|
Part 2: MP Ctrough at Steady State of Dostarlimab
Lasso di tempo: Up to 168 days
|
Up to 168 days
|
|
|
Part 2: MP AUC at Steady State of Dostarlimab
Lasso di tempo: Up to 168 days
|
Up to 168 days
|
|
|
Part 2: MP Cmax of Dostarlimab
Lasso di tempo: Up to 168 days
|
Up to 168 days
|
Collaboratori e investigatori
Sponsor
Investigatori
- Direttore dello studio: GSK Clinical Trials, GlaxoSmithKline
Studiare le date dei record
Studia le date principali
Inizio studio (Stimato)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie urogenitali
- Malattie genitali
- Neoplasie urogenitali
- Neoplasie per sede
- Neoplasie
- Malattie urogenitali femminili
- Malattie urogenitali femminili e complicanze della gravidanza
- Malattie uterine
- Malattie genitali, femmina
- Neoplasie genitali, femmina
- Neoplasie uterine
- Neoplasie endometriali
- Prodotti chimici organici
- Idrocarburi
- Cicloparaffins
- Idrocarburi, aliciclici
- Idrocarburi, ciclici
- Terpeni
- Complessi di coordinamento
- Taxoidi
- Ciclodecani
- Diterpenes
- Carboplatino
- Paclitaxel
- Dostarlimab
Altri numeri di identificazione dello studio
- 300118
- 2025 (Sovvenzione/contratto NIH degli Stati Uniti)
- 2025-525060-15-00 (Ctis)
- EN-35 (Altro identificatore: ENGOT Number)
- GOG-3125 (Altro identificatore: GOG Number)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
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
Periodo di condivisione IPD
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.
Criteri di accesso alla condivisione IPD
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.
Tipo di informazioni di supporto alla condivisione IPD
- STUDIO_PROTOCOLLO
- LINFA
- ICF
- RSI
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .