A Study to Investigate GSK5733584 as Maintenance Treatment for Participants With MMRp Endometrial Cancer (BEHOLD-Endometrial02)

A Randomized, Open-label, Multicenter, Phase 3 Study to Investigate GSK5733584 in Combination With Immune Checkpoint Inhibition for Maintenance Treatment of Participants With Mismatch Repair Proficient (MMRp) Endometrial Cancer

The purpose of this study is to see how well GSK5733584 in combination with standard treatment of choice works as maintenance therapy in participants with advanced or recurrent endometrial cancer (EC) compared to current standard of care. The study will also assess whether drug combination is safe and tolerated well by participants compared to the usual care and will help us better understand its impact on Health-Related Quality of Life of participants.

Study Overview

• Status: Not yet recruiting
• Conditions: Neoplasms, Endometrial
• Intervention / Treatment: Drug: Pembrolizumab; Drug: GSK5733584; Drug: Dostarlimab

• Study Type: Interventional
• Enrollment (Estimated): 610
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is at least 18 years of age and the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the Informed consent form (ICF).
• Has received 6 cycles of first-line therapy (i.e. induction therapy), consisting of platinum-based doublet chemotherapy (carboplatin/paclitaxel) with immune checkpoint inhibition as part of standard of care (either pembrolizumab or dostarlimab) or via trial Run-In (dostarlimab). Completion of 4 cycles is permitted if the reason for discontinuation of therapy was due to chemotherapy toxicity and the participant has completed at least 12 weeks of immunotherapy during induction.
• Is deemed suitable to continue with maintenance therapy with immune checkpoint inhibition (dostarlimab or pembrolizumab).
• Demonstrates no clinical or radiographic progression of disease per investigator after the final dose of induction therapy. Final dose is defined as the last day that either platinum chemotherapy, taxane chemotherapy or immune checkpoint inhibition was given within the last cycle of induction therapy
• Has histologically confirmed endometrial carcinoma including but not limited to endometrioid, serous, clear cell and endometrial carcinosarcoma. Mixed epithelial carcinomas are permitted.

• Meets one of the following criteria:

  • Has newly diagnosed stage III disease [2023 International Federation of Gynecology and Obstetrics (FIGO) staging] with measurable residual disease >1 cm after primary debulking surgery (incomplete cytoreduction).
  • Has newly diagnosed stage III disease (2023 FIGO staging) that is not suitable for primary debulking surgery with measurable disease.
  • Has newly diagnosed stage IV disease (2023 FIGO staging) and any residual disease status (measurable or non-measurable) following debulking surgery. Participants not suitable for primary debulking surgery are also permitted.
  • Has recurrent disease and is naïve to systemic anticancer therapy and any disease status (measurable or non-measurable).
  • Has recurrent disease after receiving prior neo-adjuvant/adjuvant systemic anticancer therapy and had a recurrence >12 months after last dose of neo-adjuvant/adjuvant treatment. Participants with any disease status (measurable or non-measurable) are permitted.
• Has a tumor demonstrating either Mismatch Repair proficient (MMRp) or Microsatellite stable (MSS),(NGS); MSS.
• Has provided a Formalin fixed, paraffin embedded (FFPE) tumor tissue sample sufficient for the central assessment of B7 homolog 4 protein (B7-H4) expression and MMR (if local MMRp/MSS test result(s) not available), with the result of B7-H4 expression testing available prior to date of randomization.
• Is willing to use adequate contraception. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

• Mesenchymal tumors of the uterus (uterine sarcomas) and neuroendocrine uterine cancer.
• Has a malignancy (except disease under study) that has progressed or required active treatment within 36 months prior to date of randomization except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas.
• Any evidence of current Interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis.
• Has experienced any of the following with prior immunotherapy: any imAE ≥ Grade 3, immune-mediated severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson syndrome [SJS], Toxic Epidermal Necrolysis [TEN], or Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS] syndrome, or myocarditis of any grade.
• Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to ≤ Grade 1 or to the baseline status preceding prior therapy, excluding alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 neuropathy, or adverse reactions that the investigator, with the agreement of the sponsor, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study.
• Has had any major surgery within 28 days prior to date of C1D1 or received focal radiotherapy within 21 days prior to date of C1D1.
• Has received treatment with an investigational agent within 30 days prior to C1D1.
• Has received prior therapy with topoisomerase I inhibitors (e.g. irinotecan or topotecan) or Antibody-Drug Conjugate (ADC)with a topoisomerase I inhibitor warhead, B7-H4 targeted therapy, or immune checkpoint inhibitor.
• Has received treatment with strong or moderate inhibitor of Cytochrome P450 (CYP) 3A4 or CYP2D6, strong or moderate inducer of CYP3A4, inhibitor of P-glycoprotein (P-gp) or Breast cancer resistant protein (BCRP), or inducer of P-gp within 14 days prior to date of C1D1 or anticipates their use during study participation and up to 30 days after the last dose of study intervention administration.
• Use drugs known to prolong the QT interval or potentially cause torsades de pointes; or need to continue these medications during the study and up to 30 days after the last dose of study intervention.
• Has received any transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including Granulocyte-Colony Stimulating Factor [G-CSF], Granulocyte-Macrophage Colony-Stimulating Factor [GM-CSF], or recombinant erythropoietin) within 14 days prior to C1D1.
• Has an Alanine aminotransferase (ALT) value >2.5 × Upper limit of normal (ULN) or for participants with documented liver metastases/tumor infiltration has an ALT value >5 × ULN.
• Has a total bilirubin value >1.5 × ULN.
• Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice. Participants who exhibit these signs or symptoms as a result of the malignancy under investigation and whose conditions are deemed adequately controlled by the investigator may be eligible for inclusion.
• Has Corrected QT interval (QTc) >470 milliseconds (msec).
• Has a history of congenital long QT syndrome or has a history of or evidence of cardiac abnormalities within 12 months prior to screening such as serious, uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.
• Has any active renal condition (e.g., infection, requirement for dialysis, or any other significant renal condition that could affect the participant's safety).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK5733584 plus Standard of Care (SOC); Participants will receive GSK5733584 along with SOC (Dostarlimab or Pembrolizumab)	Drug: GSK5733584; GSK5733584 will be administered
Active Comparator: Standard of Care; Participants will receive standard of care (Dostarlimab or Pembrolizumab) as per investigator's discretion	Drug: Pembrolizumab; Pembrolizumab will be administered; Drug: Dostarlimab; Dostarlimab will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) by BICR assessment	PFS is defined as the time from the date of randomization to the date of first documented Progressive Disease (PD) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) by Blinded independent central review (BICR) assessment or death from any cause, whichever occurs first	Up to approximately 151 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause	Up to approximately 263 weeks
PFS by investigator assessment	PFS is defined as the time from the date of randomization to the date of first documented PD per RECIST 1.1 by investigator assessment or death from any cause, whichever occurs first	Up to approximately 151 weeks
Objective response rate (ORR) by investigator assessment	ORR is defined as the percentage of participants with best overall response of either complete response (CR) or partial response (PR) per RECIST 1.1 by investigator assessment	Up to approximately 263 weeks
ORR by BICR assessment	ORR is defined as the percentage of participants with best overall response of either CR or PR per RECIST 1.1 by BICR assessment	Up to approximately 263 weeks
Duration of Response (DOR) by investigator assessment	DOR is defined as the time from the date of first documented objective response (CR or PR) to the date of first documented PD per RECIST 1.1 by investigator assessment or death from any cause, whichever comes first	Up to approximately 263 weeks
DOR by BICR assessment	DOR is defined as the time from the date of first documented objective response (CR or PR) to the date of first documented PD per RECIST 1.1 by BICR assessment or death from any cause, whichever comes first	Up to approximately 263 weeks
Progression Free Survival on subsequent line of therapy (PFS2)	PFS2 is defined as the time from the date of randomization to the date of first documented investigator-assessed clinical or radiographical progression following the first subsequent anticancer therapy and after the progression event used for PFS, or death from any cause, whichever occurs first	Up to approximately 263 weeks
Time to first subsequent therapy or death (TFST)	TFST is defined as the time from the date of randomization to the date of initiation of subsequent therapy or death from any cause, whichever occurs first	Up to approximately 263 weeks
Time to second subsequent therapy (TSST)	TSST is defined as the time from the date of randomization to the date of initiation of second subsequent therapy or death from any cause, whichever occurs first	Up to approximately 263 weeks
Pharmacokinetic (PK) concentration of GSK5733584 (conjugated antibody and payload)		Up to approximately 263 weeks
Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb) against GSK5733584		Up to approximately 263 weeks
Titers of ADA against GSK5733584		Up to approximately 263 weeks
Number of participants with Treatment-emergent adverse event (TEAEs), Adverse event of special interest (AESIs), Immune-mediated adverse event (imAEs) and Treatment-emergent serious adverse event (TESAEs)		Up to approximately 263 weeks
Number of participants with TEAEs/AESI/imAEs/TESAEs leading to dose modifications or study intervention discontinuation		Up to approximately 263 weeks
Number of participants with changes in vital signs, laboratory tests (hematology and clinical chemistry), and Electrocardiogram (ECG)		Up to approximately 263 weeks
Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score	The EORTC QLQ-C30 includes 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. Participants responses on these items are averaged and then transformed to scores ranging from 0 to 100. For items related to function and global health status, a higher score indicates better functioning or a better overall state of health, while, for symptom-related items, a higher score denotes more severe symptoms.	Up to approximately 263 weeks
Change from baseline in EORTC QLQ- Endometrial Cancer Module (EN24) score	The EORTC QLQ-EN24 includes a 24-item questionnaire for evaluating endometrial cancer-specific symptoms and concerns in participants of cancer clinical studies. Participants responses are averaged and then transformed to a score ranging from 0 to 100. For functional and global health items, a higher score indicates better functioning or a better overall state of health, while for symptom items, a higher score indicates more severe symptoms.	Up to approximately 263 weeks
Time to deterioration (TTD) of EORTC QLQ-EN24	TTD is defined as the time from date of randomization to the first confirmed clinically meaningful deterioration on any of the domains of EORTC QLQ-EN24: lymphoedema, urological symptoms, gastrointestinal symptoms, and pain in back and pelvis	Up to approximately 263 weeks
TTD of EORTC QLQ-C30	TTD is defined as the time from date of randomization to the first confirmed clinically meaningful deterioration on any of the domains of EORTC QLQ-C30: physical functioning, role functioning, and Global Health Status (GHS) /Quality of Life (QoL)	Up to approximately 263 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: GOG, ENGOT

Study record dates

Study Major Dates

• Study Start (Estimated): September 3, 2026
• Primary Completion (Estimated): July 23, 2029
• Study Completion (Estimated): September 18, 2031

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Pembrolizumab; Antibody-Drug Conjugate; Endometrial Cancer; Dostarlimab; GSK5733584; BEHOLD-Endometrial02
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; pembrolizumab; dostarlimab
• Other Study ID Numbers: 224039; 2025-523363-37 (Other Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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 Time Frame: 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 asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: 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 Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No