TITRE (EN) A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 for Injection in Subjects With Advanced Solid Tumors
PROTOCOLE ID BEHOLD-1
CLINICAL TRIAL.gov ID NCT06431594
TYPE(S) DE CANCER Endomètre
PHASE Phase I
TYPE D'ÉTUDE Clinique
INSTITUTION CHUM
1051 rue Sanguinet
(514) 890-8000
VILLE Montréal
INVESTIGATEUR(RICE) PRINCIPAL(E) Diane Provencher
COORDONATEUR(RICE) Adeline Hamon
parc.eligibilite.chum@ssss.gouv.qc.ca
514-890-8000 poste 30737
STATUT  Actif en recrutement
CRITÈRES D'ÉLIGIBILITÉ (EN)
  • 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).
  • 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.

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.
  • Maintenance therapy will be considered part of the preceding line of therapy (ie, not counted independently).

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 2 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.
  • Maintenance therapy will be considered part of the preceding line of therapy (ie, not counted independently
  • All epithelial histologies are permitted including carcinosarcoma.
CRITÈRES D'EXCLUSION (EN)
  • 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 4 weeks 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 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.