A Study of Dostarlimab in Combination With Carboplatin-paclitaxel in Chinese Participants With Primary Advanced or Recurrent Endometrial Cancer (EC)

Official title

A Phase 2, Multicenter, Open-label, Single Arm Study of Dostarlimab Plus Carboplatin-paclitaxel Followed by Dostarlimab Monotherapy in Participants With dMMR/MSI-H Primary Advanced or Recurrent Endometrial Cancer in China (China RUBY)

Overview

The goal of this clinical trial is to see how well dostarlimab works when administered with the chemotherapy drugs carboplatin and paclitaxelin in treating EC in Chinese participants. The study aims to understand the treatments effectiveness, safety, how the drugs behave in the body, and whether it causes any immune reactions.

Interventions

• Biological Dostarlimab
  Dostarlimab will be administered.
• Drug Carboplatin
  Carboplatin will be administered.
• Drug Paclitaxel
  Paclitaxel will be administered.

Primary outcome measures

• Durable Response Rate for 12 months (DRR12) assessed by Blinded Independent Central Review (BICR) [Time frame: Up to approximately 148 weeks]

Secondary outcome measures (12)

• DRR12 assessed by Investigator [Time frame: Up to approximately 148 weeks]
• Progression-free survival (PFS) per RECIST 1.1, assessed by BICR [Time frame: Up to 226 weeks]
• Progression-free survival (PFS) per RECIST 1.1, assessed by investigator [Time frame: Up to 226 weeks]
• Overall survival (OS) [Time frame: Up to 226 weeks]
• Overall response rate (ORR) per RECIST 1.1 assessed by BICR [Time frame: Up to 226 weeks]
• ORR per RECIST 1.1 assessed by Investigator [Time frame: Up to 226 weeks]
• Duration of response (DOR) per RECIST 1.1 assessed by BICR [Time frame: Up to 226 weeks]
• DOR per RECIST 1.1 assessed by Investigator [Time frame: Up to 226 weeks]
• Serum concentration of dostarlimab [Time frame: Up to 67 weeks]
• Concentration at the end of infusion (C-EOI) for dostarlimab [Time frame: Up to 67 weeks]
• Trough concentration (Ctrough) for dostarlimab [Time frame: Up to 67 weeks]
• Number of participants with Anti-drug antibody (ADA) against dostarlimab [Time frame: Up to 226 weeks]

Eligibility criteria

Inclusion criteria

• Participant has histologically or cytologically proven EC with recurrent or advanced disease.
• Participant has molecular subtype of defective mismatch repair (dMMR) or microsatellite instability high (MSI-H) determined by the central reference laboratory before study intervention.
• Participant must have primary Stage III or Stage IV disease or first recurrent EC with a low potential for cure by radiation therapy or surgery alone or in combination, and presence of at least one target lesion per RECIST 1.1 based on Investigator's assessment and meet at least 1 of the following criteria:

• Has primary Stage III to IV disease and is naive to systemic anticancer therapy for EC;
• Has first recurrent disease and is naïve to systemic anticancer therapy for EC;
• Had received prior neo-adjuvant/adjuvant anticancer therapy and had a recurrence or PD ≥6 months after completing treatment (first recurrence only).
• Participant has adequate archive tumor tissue sample for MMR/MSI status testing. If no archival tissue is available, tissue sample must be obtained before study intervention.
• Participant is not pregnant or breastfeeding and agrees to use a highly effective contraceptive method during the study period if a woman of childbearing potential (WOCBP).
• Participant has an Eastern Cooperative Oncology Group Performance status (ECOG PS) of 0 or 1.
• Participant has adequate organ function, as assessed by hematologic, renal, hepatic and coagulation parameters.

Exclusion criteria

• Participant has a concomitant malignancy, or participant has a prior non-endometrial invasive malignancy who has been disease-free for <3 years or who received any active treatment in the last 3 years for that malignancy. Non-melanoma skin cancer is allowed.
• Participant has any medical history of interstitial lung disease or pneumonitis.
• Participant has cirrhosis or current unstable liver or biliary disease.
• Participant has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both.
• Participant has a diagnosis of immunodeficiency.
• Participant has received prior therapy with an anti- Programmed death protein 1 (PD-1), anti- Programmed death ligand 1 (PD-L1), anti- Programmed death ligand 2 (PD-L2), or anti- Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) agent.
• Participant has not recovered adequately from AEs.
• Participant has received prior anticancer therapy (chemotherapy, targeted therapies, hormonal therapy, radiotherapy, or immunotherapy) within 21 days prior to the first dose of study intervention.
• Participant has received any live vaccine within 30 days of the first dose of study intervention. Vaccination against coronavirus disease 2019 (COVID-19) using vaccines that are authorized via the appropriate regulatory mechanisms are not exclusionary.
• Participant has Hepatitis B surface antigen (HBsAg) positive, or Hepatitis C virus (HCV) Ribonucleic acid (RNA) positive at screening or within 3 months prior to the first dose of study intervention.
• Participant is known human immunodeficiency virus (HIV) infection.
• Participant is currently participating and receiving study intervention or has participated in a study of an investigational agent and received study intervention or used an investigational device within 4 weeks of the first dose of treatment.
• Participant with contraindication to carboplatin and paclitaxel.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• GSK Investigational Site — Jinan

Identifiers

NCT: NCT07108270 · 222258

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗