A Study to Investigate GSK5733584 Compared With Chemotherapy in Participants With Recurrent Endometrial Cancer (BEHOLD-Endometrial01)

NCT07286331 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 2240382025-523362-25-00
• Study Type: interventional
• Target: 600
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study specifically aims to evaluate how well GSK5733584 works in treating Endometrial Cancer (EC) compared to standard of care. The study also assesses whether GSK5733584 is safe and tolerated well by participants in comparison to standard of care and will help provide a better understanding of the main side effects of the drugs

Conditions

Neoplasms, Endometrial

Keywords

Endometrial Cancer; GSK5733584; Paclitaxel; Doxorubicin; Antibody-drug conjugate; BEHOLD-Endometrial01

Outcome Measures

Primary Outcomes (2)

• Objective response rate (ORR) by BICR

  ORR is defined as the percentage of participants with best overall confirmed response of either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) by Blinded independent central review (BICR)

  Up to approximately 97 weeks

• Progression Free Survival (PFS) by BICR

  PFS is defined as the time from the date of randomization to the date of first documented Progressive Disease (PD) or death from any cause, whichever occurs first per RECIST 1.1 by BICR assessment

  Up to approximately 97 weeks

Secondary Outcomes (16)

• Overall Survival (OS)

  Up to approximately 156 weeks

• ORR by investigator assessment

  Up to approximately 156 weeks

• Duration of Response (DOR) by BICR

  Up to approximately 156 weeks

• DOR by investigator assessment

  Up to approximately 156 weeks

• PFS by investigator assessment

  Up to approximately 156 weeks

Study Arms (2)

GSK5733584

EXPERIMENTAL

Participants will receive GSK5733584

Drug: GSK5733584

Standard of Care

ACTIVE COMPARATOR

Participants will receive standard of care treatment (Paclitaxel or Doxorubicin) as per investigator's discretion

Drug: Paclitaxel; Drug: Doxorubicin

Interventions

GSK5733584 DRUG

GSK5733584 will be administered

GSK5733584

Paclitaxel DRUG

Paclitaxel will be administered

Standard of Care

Doxorubicin DRUG

Doxorubicin will be administered

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• 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 histologically confirmed recurrent or persistent endometrial carcinoma including but not limited to endometroid, serous, clear cell, and endometrial carcinosarcoma. Mixed epithelial carcinomas are permitted.
• Has undergone at least 1 and no more than 2 lines of prior systemic treatment for EC. Up to 3 lines of prior systemic treatment are acceptable if one line was administered in the adjuvant/neo-adjuvant setting. The definition of prior lines of therapy is as follows:
• Adjuvant ± neo-adjuvant therapy counts as one line of treatment.
• Maintenance therapy is considered part of the preceding line and does not count as an independent line.
• Switching to another agent within the same class due to toxicity (without disease progression) is considered part of the same line of therapy.
• Unplanned addition or switching to a new drug in a different class is considered a separate line of therapy.
• Hormonal therapy is NOT counted as a separate line.
• Must have received prior platinum-based chemotherapy and anti- Programmed cell death 1 (PD-1) /anti- Programmed cell death ligand 1 (PD-L1) therapy, either separately or in combination. Participants deemed unsuitable for a prior PD-1/PD-L1 inhibitor therapy (contraindications such as immunodeficiency, autoimmune disease that required systemic treatment) as determined by the investigator or treating physician are eligible.
• Participants must have a platinum-free interval of less than 12 months if they previously received platinum-based therapy solely in the adjuvant setting.
• If PD-L1/PD-1 inhibitor therapy was administered with platinum-based treatment, participant is eligible regardless of whether the Platinum-free interval (PFI) exceeds 12 months.
• Participants with metastatic disease who underwent treatment including gynecological surgery followed by a platinum-based regimen, or those deemed intolerant to platinum-based therapy, are eligible regardless of whether the PFI exceeds 12 months.
• Has provided a Formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample sufficient for the central assessment of B7 homolog 4 protein (B7-H4) expression, with the result of B7-H4 expression testing available prior to date of randomization.
• Has ≥1 Target Lesion per RECIST 1.1 by BICR eligibility review of screening scans.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• 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 the past 36 months prior to date of randomization except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas \[e.g., breast, cervix, bladder\] that have been resected with no evidence of metastatic disease, or that is otherwise considered cured by the investigator.
• Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
• Has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
• Has untreated brain or Central nervous system (CNS) metastases or brain/CNS metastases that have progressed (e.g., evidence of new or enlarging brain metastasis or new neurologic symptoms attributable to brain/CNS metastases). Participants with previously treated and clinically stable brain/CNS metastases and who have completed all corticosteroid therapy for ≥14 days before date of C1D1 are not excluded from participation.
• Has any evidence of current Interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis.
• 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 and endocrinopathy managed with replacement therapy, or that the investigator, with the agreement of the sponsor, considers to be stable or not clinically relevant for the tolerability of study intervention in the current clinical study.
• Has any serious and/or unstable medical or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant's safety, obtainment of informed consent, or compliance to the study procedures.
• Has had any major surgery within 28 days prior to date of C1D1 or history of local radiotherapy within 21 days prior to C1D1.
• Has received treatment with an investigational agent within 30 days prior to C1D1.
• Has received prior therapy with Topo1i (e.g. irinotecan or topotecan) or ADC with a Topo1i warhead, or B7-H4 targeted therapy.
• Has received treatment with any cytotoxic chemotherapy drugs or other antitumor drugs (including endocrine therapy, molecular targeted therapy, immunotherapy, biotherapy and investigational drug) within 30 days or 5 half-lives, whichever is shorter, prior to C1D1; or need to continue these drugs during the study.
• Has received any live vaccine within 30 days prior to C1D1.Note: mRNA and adenoviral-based Coronavirus disease 2019 (COVID-19) vaccines are considered non-live.
• Has received treatment with strong or moderate inhibitor of Cytochrome P450 (CYP) 3A4 or CYP2D6, strong or moderate inducer of CYP3A, 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 last dose of study intervention.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator
• GOG Foundation: collaborator

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Paclitaxel; Doxorubicin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The independent central reviewer assessing primary outcome data will be masked (blinded) from participants treatment assignment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2025
• First Posted: December 16, 2025
• Study Start (Estimated): June 9, 2026
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): May 30, 2029
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.