A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of GSK5764227 in Participants with Advanced Solid Tumors
A Phase 1 study of GSK5764227 in participants with advanced solid tumors
Ishibashi Hideyasu
GlaxoSmithKline K.K.
Akasaka Intercity AIR, 1-8-1 Akasaka, Minato-ku, Tokyo, Japan
+81-120-561-007
jp.gskjrct@gsk.com
Ishibashi Hideyasu
GlaxoSmithKline K.K.
Akasaka Intercity AIR, 1-8-1 Akasaka, Minato-ku, Tokyo, Japan
+81-120-561-007
jp.gskjrct@gsk.com
Recruiting
Oct. 31, 2024
15
Interventional
non-randomized controlled trial
open(masking not used)
uncontrolled control
single assignment
treatment purpose
-Male or female participants at least 18 years of age (>-18 years)
-Participants with histologically confirmed advanced/metastatic solid tumors, irrespective of mutational status, as defined per study phase and cohort, as follows:
-Participants with advanced/metastatic tumors who have progressed on or are intolerant to all available standard of care therapies.
-Participants with selected advanced/metastatic solid tumors who have progressed on one or more prior lines of therapy.
-Has measurable disease (i.e., at least 1 target lesion) per RECIST v1.1, as determined by the investigator.
-Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose.
-Has a life expectancy >12 weeks.
-Has adequate organ function. Specimens must be collected within 3 days prior to the start of study intervention administration.
-Where available, participants should provide a formalin fixed and paraffin embedded (FFPE) tumor sample from the most recent biopsy of primary cancer or from a metastatic site for central testing. Tumor tissue (archival tumor tissue or a fresh biopsy) is required unless an exemption is granted by the medical monitor. Tumor tissue is necessary for retrospective detection of B7 homolog 3 protein (B7-H3) expression by Immunohistochemistry (IHC) in central laboratory and other biomarker analysis.
-Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to <-Grade 1 or to the baseline status preceding prior therapy.
-Prior treatment with orlotamab, enoblituzumab, I-Dxd, or other B7-H3 targeted agents.
-Evidence of brain metastasis (unless meeting the following criteria at the same time: asymptomatic; medically stable for at least 4 weeks prior to initial dosing; no steroid treatment required for at least 2 weeks prior to initial dosing; and no imaging evidence of severe edema located around the tumor lesion); or untreated progression due to brain metastasis during or after the last treatment prior to screening; or evidence of meningeal/brainstem metastasis; or evidence of spinal cord compression (detected by radiographic examination, symptomatic or not).
-Any of the following cardiac examination abnormality:
-Has QT interval, corrected for heart rate (QTc) >450 msec or QTc >480 msec for participants with bundle branch block.
-Evidence of current clinically significant arrhythmias or ECG abnormalities (e.g., complete left bundle branch block, third-degree atrioventricular [AV] block, second-degree AV block, PR interval >250 msec).
-Risk factors of prolonged QTc or arrhythmia events, such as heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death of any direct relative under 40 years old or any concomitant medications that prolong the QT interval.
-Left ventricular ejection fraction (LVEF) <50%.
-Has severe, uncontrolled or active CV 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 non-infectious pneumonitis requiring high-dose glucocorticoids.(Japan-Specific Requirements) Any evidence of current pneumonitis or ILD, or a prior history of pneumonitis requiring high-dose systemic glucocorticoids or ILD.
18age old over
No limit
Both
Advanced solid tumors
Drug: GSK5764227
GSK5764227 will be administered as an IV infusion
Drug: Topotecan
Topotecan will be administered as an IV infusion
Phase 1a:
-Number of participants with Adverse Events (AEs)
-Number of participants with Dose Limiting Toxicities (DLTs)
-Number of participants with AEs and serious adverse events (SAEs) by severity
-Number of participants with AEs leading to dose modifications
-Number of participants with changes in vital signs, body weight, laboratory tests, electrocardiogram (ECG) and Eastern Cooperative Oncology Group (ECOG) performance status
Phase 1a and Phase 1b:
-Maximum concentration (Cmax) of GSK5764227
-Time to reach maximum concentration (Tmax) of GSK5764227
-Area under concentration from 0 to t (AUC 0-t) of GSK5764227
-Trough concentration (Ctrough) of GSK5764227 (conjugated antibody, total antibody, small-molecule toxin)
Phase 1a:
-Objective Response Rate
Phase 1a and Phase 1b:
-Disease control rate (DCR)
-Duration of Response (DoR)
-Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb)
-Titers of ADA against GSK5764227
Phase 1b:
-Number of participants with AEs and serious adverse events (SAEs) by severity
-Number of participants with AEs leading to dose modifications
-Number of participants with changes in vital signs, body weight, laboratory tests, electrocardiogram (ECG) and ECOG performance status
-Overall Survival (OS)
-Progression-Free Survival (PFS)
GlaxoSmithKline K.K.
to be updated after the approval of IRB
to be updated after the approval of IRB, Tokyo
Not approval
No
NCT06551142
ClinicalTrials.gov
United States/Argentina/Canada/France/Italy/Spain/United Kingdom
