A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 for Injection in Subjects With Advanced Solid Tumors

Study Identifier:
222730
CT.gov Identifier:
NCT06431594
EudraCT Identifier:
202451000000
EU Trial (CTIS) Number:
2024-513860-25-00
Study Contact Information:
N/A
Recruiting

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Study Summary

The goal of this study is to assess the safety and tolerability of GSK5733584. The study will also see how the levels of GSK5733584 change over time at different dose amount. To evaluate GSK’584 in patients with advanced solid tumors, including platinum-resistant OC (PROC) and EC. Part 1a (dose escalation) assesses safety, tolerability, pharmacokinetics (PK), and immunogenicity of GSK’584 in 26-40 patients with advanced solid tumors refractory/intolerant to established therapies. Part 1b (dose expansion) assesses clinical activity, safety, and PK of GSK’584 in PROC (N≈90) and EC (N≈60) expansion cohorts in 2-3 selected dose levels.

To evaluate the safety, tolerability and efficacy of Mo-Rez injection in patients with PROC or advanced/recurrent EC. Phase Ia assessed up to four Mo-Rez dose levels in patients with advanced solid tumors, with intravenous administration every three weeks until progression or toxicity.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
  • Neoplasms
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
    N/A
    Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • Males or females aged 18 years or older (≥18 years).
    • Participants with pathologically confirmed advanced solid tumor (who have failed or are intolerant to standard of care).
    • PROC cohort
    • Histologically documented, advanced (metastatic and/or unresectable) high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer.
    • Must have received or are intolerant to 1 but no more than 3 lines of prior systemic therapy.
    • Platinum-resistant disease, defined as progression or relapse within 6 months after the completion of platinum-based therapy.
    • Must have had prior bevacizumab if the participant was considered a candidate for this regimen and the regimen is locally available.
    • Participants with known Folate receptor-α (FR-α) expressing tumors must have received mirvetuximab soravtasine if the participants was considered a candidate for this regimen and the regimen is locally available.
    • Participants with known Breast cancer susceptibility gene (BRCA) mutated tumors should have received a Poly adenosine diphosphate-ribose polymerase (PARP) inhibitor if the participant was considered a candidate for this regimen and the regimen is locally available.
    • Endometrial cancer cohort
    • Histologically documented, advanced (metastatic and/or unresectable) or recurrent endometrial cancer.
    • Must have received or are intolerant to 1 but no more than 3 lines of prior systemic therapy.
    • Must have had prior platinum and PD(L)-1 inhibitor (in same regimen or in separate regimens), if considered a candidate for this regimen and the regimen is locally available.
    • All epithelial histologies are permitted including carcinosarcoma.
    • Participants have at least one target lesion as assessed per the RECIST 1.1
    • Tumor tissue from a newly obtained biopsy or archival tumor tissue is required for retrospective detection of B7 homolog 4 (B7-H4) expression by Immunohistochemistry (IHC) in central laboratory and other biomarker analysis. Tissue from a newly obtained biopsy is preferred. If a newly obtained biopsy is not feasible, archival tumor tissue within 2 years prior to the first dose of study drug is acceptable.
    • Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 2 and no deterioration within 2 weeks before the first dose.
    • Have a life expectancy of at least 12 weeks.
    Exclusion criteria
    • Have received any of B7-H4-targeted therapies.
    • Have received any of cytotoxic chemotherapy drugs, anti-tumor traditional Chinese medicines or other anti-tumor drugs within 28 days prior to the first dose of study drug; or need to continue these drugs during the study.
    • Have received locoregional radiation therapy within 2 weeks prior to the first dose of study drug; more than 30% of bone marrow irradiation or wide-field radiation therapy within 4 weeks prior to the first dose of study treatment.
    • Presence of pleural/abdominal effusion/ascites requiring clinical intervention; presence of pericardial effusion
    • Major surgery within 28 days prior to the first dose of study treatment.
    • Evidence of brain metastasis unless asymptomatic.
    • Has inadequate bone marrow reserve or hepatic/renal functions.
    • Mean Fridericia-corrected QT interval (QTcF) > 470 millisecond (msec) on resting ECG.
    • Evidence of current clinically significant arrhythmias or ECG abnormalities
    • Risk factors of prolonged QTc or arrhythmia events,
    • Left ventricular ejection fraction (LVEF) < 50%.
    • Have severe, uncontrolled or active cardiovascular disorders, serious or poorly controlled hypertension, clinically significant bleeding symptoms or serious arteriovenous thromboembolic events
    • Any evidence of current Interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or pneumonitis requiring high-dose systemic glucocorticoids.
    • Have received prior therapy with topoisomerase inhibitors or topoisomerase inhibitor Antibody-drug conjugate (ADCs)
    • PROC
    • Primary platinum refractory disease defined as those who have progressed on or within 12 weeks of last dose of first line platinum therapy not permitted.
    • Non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade serous, or low-grade endometrioid carcinoma not permitted.
    • Endometrial cancer a. Mesenchymal tumors of the uterus (uterine sarcomas) not permitted.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Mountain Region
    West Valley City, UT, United States, 84119
    Investigator
    William McKean
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Neoplasms
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Nehal Lakhani
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Neoplasms
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Neoplasms