A Study of GSK5764227 in Participants With Advanced Solid Tumors
- Registration Number
- NCT06551142
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
The goal of this study is to assess the safety and tolerability of GSK5764227. The study will also see how the levels of GSK5764227 change over time at different dose amounts.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 240
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Male or female participants at least 18 years of age (≥18 years)
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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.
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Has measurable disease (i.e., at least 1 target lesion) per RECIST v1.1, as determined by the investigator.
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Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose.
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Has a life expectancy >12 weeks.
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Has adequate organ function. Specimens must be collected within 3 days prior to the start of study intervention administration.
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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.
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Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to ≤Grade 1 or to the baseline status preceding prior therapy.
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Prior treatment with orlotamab, enoblituzumab, I-Dxd, or other B7-H3 targeted agents.
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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).
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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%.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1a: Dose escalation-GSK5764227 GSK5764227 - Phase 1b: Dose expansion-GSK5764227 GSK5764227 - Phase 1b: Dose expansion- Topotecan Topotecan -
- Primary Outcome Measures
Name Time Method Phase 1a: Number of participants with Adverse Events (AEs) Up to approximately 28 months Phase 1a: Number of participants with AEs leading to dose modifications Up to approximately 28 months Phase 1a: Number of participants with Dose Limiting Toxicities (DLTs) Up to 21 days Phase 1a: Number of participants with AEs and serious adverse events (SAEs) by severity Up to approximately 30 months Phase 1a: Number of participants with changes in vital signs, body weight, laboratory tests, electrocardiogram (ECG) and Eastern Cooperative Oncology Group (ECOG) performance status Up to approximately 28 months Phase 1b: Objective Response Rate (ORR) Up to approximately 27 months ORR is defined as the proportion of participants who have confirmed Complete response (CR) or Partial response (PR), assessed by the investigator according to RECIST V1.1 criteria
Phase 1b: Progression-free survival (PFS) Up to approximately 27 months PFS is defined as the time from the date of randomization until the earliest date of documented disease progression as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) criteria or death due to any cause
- Secondary Outcome Measures
Name Time Method Phase 1a and Phase 1b: Maximum concentration (Cmax) of GSK5764227 Up to approximately 28 months Phase 1a and Phase 1b: Trough concentration (Ctrough) of GSK5764227 (total antibody) Up to approximately 28 months Phase 1b: Number of participants with changes in vital signs, body weight, laboratory tests, electrocardiogram (ECG) and ECOG performance status Up to approximately 28 months Phase 1b: Overall Survival (OS) Up to approximately 33 months OS is defined as survival from the date of randomization to the date of death by any cause.
Phase 1a and Phase 1b: Time to reach maximum concentration (Tmax) of GSK5764227 Up to approximately 28 months Phase 1a and Phase 1b: Trough concentration (Ctrough) of GSK5764227 (conjugated antibody) Up to approximately 28 months Phase 1a and Phase 1b: Disease control rate (DCR) Up to approximately 33 months DCR is defined as the proportion of participants who have achieved CR, PR or Stable disease (SD) using RECIST v1.1 based on investigator assessment.
Phase 1a and Phase 1b: Titers of ADA against GSK5764227 Up to approximately 30 months Phase 1b: Number of participants with AEs and serious adverse events (SAEs) by severity Up to approximately 30 months Phase 1b: Number of participants with AEs leading to dose modifications Up to approximately 27 months Phase 1a and Phase 1b: Duration of Response (DoR) Up to approximately 33 months DoR is defined as the time from first documented response (CR/PR) until the time of first documentation of disease progression
Phase 1a and Phase 1b: Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb) Up to approximately 30 months Phase 1b: Progression-Free Survival (PFS) Up to approximately 33 months PFS is defined as the time from the date of randomization until the earliest date of documented disease progression as assessed by the investigator according to RECIST V1.1 criteria or death due to any cause
Phase 1a: Objective Response Rate Up to approximately 33 months ORR is defined as the proportion of participants who have confirmed CR or PR, assessed by the investigator according to RECIST V1.1 criteria
Phase 1a and Phase 1b: Area under concentration from 0 to t (AUC 0-t) of GSK5764227 Up to approximately 28 months Phase 1a and Phase 1b: Trough concentration (Ctrough) of GSK5764227 (small-molecule toxin) Up to approximately 28 months
Trial Locations
- Locations (1)
GSK Investigational Site
🇯🇵Tokyo, Japan