Endometrial Carcinoma, Neoplasms, Endometrial
Conditions
Keywords
Endometrial Carcinoma, Dostarlimab, Carboplatin-Paclitaxel
Brief summary
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.
Interventions
BIOLOGICALDostarlimab
Dostarlimab will be administered as SC injection and IV infusion
Carboplatin and paclitaxel will be administered as an IV infusion
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Serum Trough Concentration (Ctrough) After First Dose of Dostarlimab | Up to 42 days |
| Part 1: Area Under the Concentration-time Curve (AUC) of Dostarlimab | Up to 42 days |
| Part 2: Observed Ctrough of Dostarlimab | Up to 168 days |
| Part 2: Model-predicted (MP) AUC of Dostarlimab | Up to 21 days |
| Part 2: MP AUC of Dostarlimab | Up to 168 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Ctrough of Dostarlimab | Up to 42 days | — |
| Part 1: AUC of Dostarlimab | Up to 42 days | — |
| Part 1: Maximum Observed Concentration (Cmax) of Dostarlimab | Up to 42 days | — |
| Part 1: Time to Peak Drug Concentration (Tmax) of Dostarlimab | 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) | 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 | Up to 39 months | — |
| Parts 1 and 2: Confirmed Overall Response Rate (ORR) | 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 |
| Parts 1 and 2: Duration of Response (DoR) | 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 |
| Parts 1 and 2: Progression-free Survival (PFS) | 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 |
| Parts 1 and 2: Overall Survival (OS) | Up to 3 years | OS is defined as the time from the date of randomization to the date of death due to any cause |
| Part 1: Number of Participants with Antidrug Antibody (ADAs) against Dostarlimab | Up to 39 months | — |
| Part 2: Number of Participants with ADAs against Dostarlimab | Up to 3 years | — |
| Part 2: MP Ctrough of Dostarlimab | Up to 168 days | — |
| Part 2: MP Ctrough at Steady State of Dostarlimab | Up to 168 days | — |
| Part 2: MP AUC at Steady State of Dostarlimab | Up to 168 days | — |
| Part 2: MP Cmax of Dostarlimab | Up to 168 days | — |
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Outcome results
None listed