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.
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 3
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: US GSK Clinical Trials Call Center
- Puhelinnumero: 877-379-3718
- Sähköposti: GSKClinicalSupportHD@gsk.com
Tutki yhteystietojen varmuuskopiointi
- Nimi: EU GSK Clinical Trials Call Center
- Puhelinnumero: +44 (0) 20 89904466
- Sähköposti: GSKClinicalSupportHD@gsk.com
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Peräkkäinen tehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: 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 |
|
Kokeellinen: 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 |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Aikaikkuna |
|---|---|
|
Part 1: Serum Trough Concentration (Ctrough) After First Dose of Dostarlimab
Aikaikkuna: Up to 42 days
|
Up to 42 days
|
|
Part 1: Area Under the Concentration-time Curve (AUC) of Dostarlimab
Aikaikkuna: Up to 42 days
|
Up to 42 days
|
|
Part 2: Observed Ctrough of Dostarlimab
Aikaikkuna: Up to 168 days
|
Up to 168 days
|
|
Part 2: Model-predicted (MP) AUC of Dostarlimab
Aikaikkuna: Up to 21 days
|
Up to 21 days
|
|
Part 2: MP AUC of Dostarlimab
Aikaikkuna: Up to 168 days
|
Up to 168 days
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Part 1: Ctrough of Dostarlimab
Aikaikkuna: Up to 42 days
|
Up to 42 days
|
|
|
Part 1: AUC of Dostarlimab
Aikaikkuna: Up to 42 days
|
Up to 42 days
|
|
|
Part 1: Maximum Observed Concentration (Cmax) of Dostarlimab
Aikaikkuna: Up to 42 days
|
Up to 42 days
|
|
|
Part 1: Time to Peak Drug Concentration (Tmax) of Dostarlimab
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: Up to 39 months
|
Up to 39 months
|
|
|
Parts 1 and 2: Confirmed Overall Response Rate (ORR)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: Up to 39 months
|
Up to 39 months
|
|
|
Part 2: Number of Participants with ADAs against Dostarlimab
Aikaikkuna: Up to 3 years
|
Up to 3 years
|
|
|
Part 2: MP Ctrough of Dostarlimab
Aikaikkuna: Up to 168 days
|
Up to 168 days
|
|
|
Part 2: MP Ctrough at Steady State of Dostarlimab
Aikaikkuna: Up to 168 days
|
Up to 168 days
|
|
|
Part 2: MP AUC at Steady State of Dostarlimab
Aikaikkuna: Up to 168 days
|
Up to 168 days
|
|
|
Part 2: MP Cmax of Dostarlimab
Aikaikkuna: Up to 168 days
|
Up to 168 days
|
Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Opintojohtaja: GSK Clinical Trials, GlaxoSmithKline
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Arvioitu)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
- Urogenitaaliset sairaudet
- Sukuelinten sairaudet
- Urogenitaaliset kasvaimet
- Neoplasmat sivustoittain
- Neoplasmat
- Naisten virtsa- ja sukupuolielinten sairaudet
- Naisten virtsa- ja sukupuolielinten sairaudet ja raskauden komplikaatiot
- Kohdun sairaudet
- Sukuelinten sairaudet, naiset
- Sukuelinten kasvaimet, naiset
- Kohdun kasvaimet
- Endometriumin kasvaimet
- Orgaaniset kemikaalit
- Hiilivety
- Sykloparaffiinit
- Hiilivedyt, aliisykliset
- Hiilivedyt, sykliset
- Terpeenit
- Koordinointikompleksit
- Taksoidit
- Syklodekaanit
- Diterpeenit
- Karboplatiini
- Paklitakseli
- dostarlimab
Muut tutkimustunnusnumerot
- 300118
- 2025 (Yhdysvaltain NIH-apuraha/sopimus)
- 2025-525060-15-00 (Ctis)
- EN-35 (Muu tunniste: ENGOT Number)
- GOG-3125 (Muu tunniste: GOG Number)
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
IPD-suunnitelman kuvaus
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-jaon aikakehys
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-jaon käyttöoikeuskriteerit
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-jakamista tukeva tietotyyppi
- STUDY_PROTOCOL
- MAHLA
- ICF
- CSR
Lääke- ja laitetiedot, tutkimusasiakirjat
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