Clinical Trials List
Protocol Number223054
NCT Number(ClinicalTrials.gov Identfier)NCT06551142
Not yet recruiting
2025-06-18 - 2027-12-31
Phase I
Recruiting6
ICD-10C00.0
Malignant neoplasm of external upper lip
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9140.0
Malignant neoplasm of upper lip, vermilion border
A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of GSK5764227 as Monotherapy and in Combination in Participants With Advanced Solid Tumors
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Trial Applicant
GlaxoSmithKline
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2026/04/09
Investigators and Locations
Co-Principal Investigator
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- YEN-TING LIN Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
- 廖斌志 Division of Hematology & Oncology
- 吳宗哲 Division of Hematology & Oncology
- James Chih-Hsin Yang Division of Hematology & Oncology
- 蔡子修 Division of General Internal Medicine
- 吳尚俊 Division of General Internal Medicine
- JIN-YUAN SHIH Division of General Internal Medicine
- 楊景堯 Division of General Internal Medicine
- Yu-Chieh Tsai Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- 徐偉勛 醫學研究部
- 廖唯昱 Division of Hematology & Oncology
- FU-JEN HSUEH Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 吳佳哲 Division of Hematology & Oncology
- 林偉哲 Division of Radiology
- 黃泰霖 Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- 黃詩喻 Division of Hematology & Oncology
- 李易濰 Division of Radiology
- 郭明濬 Division of Hematology & Oncology
- 蔡宗翰 Division of Hematology & Oncology
- 林昶廷 Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Mu-Hsin Chang Division of Hematology & Oncology
- Tien-Hua Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Ching Yun Hsieh Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- 陳珈妤 Division of Hematology & Oncology
- Yu-Min Liao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Chia-Jui Yen
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- 劉奕廷 Division of Hematology & Oncology
- Yuh-Shyan Tsai Division of Urology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Neoplasms
Objectives
This trial aims to evaluate the safety, tolerability, pharmacokinetics, and clinical response of GSK5764227 as a monotherapy and in combination therapy, and is divided into Phase 1a (dose escalation) and Phase 1b (dose optimization/dose expansion). The Phase 1b trial in this application evaluates the clinical response, safety, tolerability, and pharmacokinetics of GSK5764227 in subjects with advanced solid tumors.
Test Drug
Injectable
Active Ingredient
GSK5764227
Dosage Form
270
Dosage
100mg/vial
Endpoints
Evaluate the clinical response of GSK5764227 in patients with advanced solid tumors.
Inclution Criteria
Inclusion Criteria:
Male or female participants at least 18 years of age (≥18 years)
Participants with histologically confirmed advanced/metastatic solid tumors, as defined per study phase and cohort, as follows:
o Phase 1a:
Participants with advanced/metastatic solid tumors.
For monotherapy dose escalation: participants must have progressed on or become intolerant to all available SOC therapies.
For combination dose escalation: participants must have received 3 or fewer prior lines of systemic anticancer therapy in the advanced/metastatic setting
Has at least 1 target lesion per RECIST 1.1, 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 adequate organ function.
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 is necessary for retrospective detection of B7 homolog 3 protein (B7-H3) expression by Immunohistochemistry (IHC) and other biomarker analysis.
At least one of the following treatment combinations/monotherapy (a, b, c, or d) is clinically indicated:
Atezolizumab, durvalumab, or pembrolizumab in combination with cisplatin or carboplatin (for combination 1 only).
Atezolizumab, durvalumab, or pembrolizumab as monotherapy (for combination 2 only)
Bevacizumab as monotherapy (for combination 3 only)
Cetuximab as monotherapy (for combination 4 only)
Additional inclusion criteria for Phase 1b Chinese participants:
Chinese participants are considered eligible if they meet all of the following:
Born in mainland China, Hong Kong or Taiwan
Descendant of 2 ethnic Chinese parents and 4 ethnic Chinese grandparents
All participants who do not meet either of the above-mentioned inclusion criteria for Chinese participants will be considered as global (non-Chinese) participants.
Male or female participants at least 18 years of age (≥18 years)
Participants with histologically confirmed advanced/metastatic solid tumors, as defined per study phase and cohort, as follows:
o Phase 1a:
Participants with advanced/metastatic solid tumors.
For monotherapy dose escalation: participants must have progressed on or become intolerant to all available SOC therapies.
For combination dose escalation: participants must have received 3 or fewer prior lines of systemic anticancer therapy in the advanced/metastatic setting
Has at least 1 target lesion per RECIST 1.1, 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 adequate organ function.
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 is necessary for retrospective detection of B7 homolog 3 protein (B7-H3) expression by Immunohistochemistry (IHC) and other biomarker analysis.
At least one of the following treatment combinations/monotherapy (a, b, c, or d) is clinically indicated:
Atezolizumab, durvalumab, or pembrolizumab in combination with cisplatin or carboplatin (for combination 1 only).
Atezolizumab, durvalumab, or pembrolizumab as monotherapy (for combination 2 only)
Bevacizumab as monotherapy (for combination 3 only)
Cetuximab as monotherapy (for combination 4 only)
Additional inclusion criteria for Phase 1b Chinese participants:
Chinese participants are considered eligible if they meet all of the following:
Born in mainland China, Hong Kong or Taiwan
Descendant of 2 ethnic Chinese parents and 4 ethnic Chinese grandparents
All participants who do not meet either of the above-mentioned inclusion criteria for Chinese participants will be considered as global (non-Chinese) participants.
Exclusion Criteria
Exclusion Criteria:
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.
Primary brain tumor or 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 4 weeks prior to initial dosing; and no midline shift due to herniation); or untreated progression due to brain metastasis or primary brain tumor during or after the last treatment prior to screening; or evidence of meningeal/brainstem involvement; 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.
Has donated blood or blood products in excess of 500 mL (approximately 1 pint) within one month prior to first dose of study treatment.
Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening. Participants with prior history of autoimmune disease must be discussed with the medical monitor. Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or insulin is not exclusionary).
Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
Has received immunosuppressive agents within 30 days prior to first dose of study treatment (or requires long-term (30 days or longer) glucocorticoid therapy). Low-dose corticosteroids (prednisone ≤10 mg/day or equivalent) may be administered. Use of inhaled or topical steroids and prophylactic corticosteroids for procedures are permitted.
Participants in dehydrated condition.
Participant with history of nephrotic syndrome or Grade 3 proteinuria. Participants discovered to have ≥2 proteinuria on dipstick at screening should undergo a 24-hour urine collection and must demonstrate <2 g of protein in 24 hours to be eligible.
History of abdominal or gastrointestinal fistula, tracheoesophageal fistula or any Grade 4 fistula, gastrointestinal perforation, intra-abdominal abscess or active clinical concern for bowel obstruction.
Has any active renal condition (e.g., requirement for dialysis, or any other significant renal condition that could affect the participant's safety). NOTE: renal obstruction successfully managed by stenting is permitted.
Additional exclusion criteria for participants receiving combination therapy
Has received prior systemic anticancer therapy within 28 days of first dose of study treatment (combinations 1, 3 and 4 only).
Has experienced any of the following with prior immunotherapy: any immune-mediated adverse event [imAE] ≥ Grade 3, immune-mediated severe neurologic events of any-grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson syndrome [SJS], Toxic epidermal necrolysis [TEN], or Drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome), symptomatic pericarditis of any etiology within 6 months prior to the administration of study intervention, or myocarditis of any grade. Clinically significant laboratory abnormalities, as judged by investigator, are not exclusionary.
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.
Primary brain tumor or 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 4 weeks prior to initial dosing; and no midline shift due to herniation); or untreated progression due to brain metastasis or primary brain tumor during or after the last treatment prior to screening; or evidence of meningeal/brainstem involvement; 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.
Has donated blood or blood products in excess of 500 mL (approximately 1 pint) within one month prior to first dose of study treatment.
Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening. Participants with prior history of autoimmune disease must be discussed with the medical monitor. Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or insulin is not exclusionary).
Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
Has received immunosuppressive agents within 30 days prior to first dose of study treatment (or requires long-term (30 days or longer) glucocorticoid therapy). Low-dose corticosteroids (prednisone ≤10 mg/day or equivalent) may be administered. Use of inhaled or topical steroids and prophylactic corticosteroids for procedures are permitted.
Participants in dehydrated condition.
Participant with history of nephrotic syndrome or Grade 3 proteinuria. Participants discovered to have ≥2 proteinuria on dipstick at screening should undergo a 24-hour urine collection and must demonstrate <2 g of protein in 24 hours to be eligible.
History of abdominal or gastrointestinal fistula, tracheoesophageal fistula or any Grade 4 fistula, gastrointestinal perforation, intra-abdominal abscess or active clinical concern for bowel obstruction.
Has any active renal condition (e.g., requirement for dialysis, or any other significant renal condition that could affect the participant's safety). NOTE: renal obstruction successfully managed by stenting is permitted.
Additional exclusion criteria for participants receiving combination therapy
Has received prior systemic anticancer therapy within 28 days of first dose of study treatment (combinations 1, 3 and 4 only).
Has experienced any of the following with prior immunotherapy: any immune-mediated adverse event [imAE] ≥ Grade 3, immune-mediated severe neurologic events of any-grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson syndrome [SJS], Toxic epidermal necrolysis [TEN], or Drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome), symptomatic pericarditis of any etiology within 6 months prior to the administration of study intervention, or myocarditis of any grade. Clinically significant laboratory abnormalities, as judged by investigator, are not exclusionary.
The Estimated Number of Participants
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Taiwan
15 participants
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Global
160 participants
