Endometrial Cancer
Conditions
Interventions
Drug: GSK5733584
Drug: Paclitaxel
Drug: Doxorubicin
Sponsors
Ishibashi Hideyasu
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 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: oAdjuvant +- neo-adjuvant therapy counts as one line of treatment. oMaintenance therapy is considered part of the preceding line and does not count as an independent line. oSwitching to another agent within the same class due to toxicity (without disease progression) is considered part of the same line of therapy. oUnplanned addition or switching to a new drug in a different class is considered a separate line of therapy. oHormonal 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. oIf 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. oParticipants 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. -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. -A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: oIs a Participant of non-childbearing potential (PONCBP) OR oIs a Participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, 30 days prior to Cycle 1 Day 1 (C1D1) and during the study intervention period and for at least 8 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relation
Exclusion criteria
Exclusion criteria: 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. -Has used drugs known to prolong the QT interval or potentially cause torsades de pointes; or need to continue these medications during the study -Has received any transfusion of blood products (inc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome Measure:Overall Survival (OS) Measure Description:OS is defined as the time from the date of randomization to the date of death due to any cause Time Frame:Up to approximately 156 weeks Outcome Measure:ORR by investigator assessment Measure Description:ORR is defined as the percentage of participants with best overall confirmed response of either CR or PR per RECIST 1.1 by investigator assessment Time Frame:Up to approximately 156 weeks Outcome Measure:Duration of Response (DOR) by BICR Measure Description:DOR is defined as the time from the date of the first documented objective response (CR or PR) that is subsequently confirmed to the date of first documented PD or death due to any cause, whichever occurs first per RECIST 1.1 by BICR assessment Time Frame:Up to approximately 156 weeks Outcome Measure:DOR by investigator assessment Measure Description:DOR is defined as the time from the date of first documented objective response (CR or PR) that is subsequently confirmed to the date of first documented PD or death due to any cause, whichever occurs first per RECIST 1.1 by investigator assessment Time Frame:Up to approximately 156 weeks Outcome Measure:PFS by investigator assessment Measure Description:PFS is defined as the time from the date of randomization to the date of first documented PD or death due to any cause, whichever occurs first per RECIST 1.1 by investigator assessment Time Frame:Up to approximately 156 weeks Outcome Measure:Number of participants with Treatment-emergent adverse event (TEAEs), Adverse event of special interest (AESIs) and Treatment-emergent serious adverse event (TESAEs) Time Frame:Up to approximately 156 weeks Outcome Measure:Number of participants with TEAEs/AESIs/TESAEs leading to dose modifications or study intervention discontinuation Time Frame:Up to approximately 156 weeks Outcome Measure:Number of participants with changes in vital signs, laboratory tests (hematology and clinical chemistry), and Electrocardiogram (ECG) | — |
Contacts
Public ContactHideyasu Ishibashi
GlaxoSmithKline K.K.
Outcome results
None listed