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
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 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
- 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
- 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
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林昶廷 Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
- 李易濰 Division of Radiology
- 郭明濬 Division of Hematology & Oncology
- 蔡宗翰 Division of Hematology & Oncology
- 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
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
- Yu-Min Liao Division of Hematology & Oncology
- 陳珈妤 Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Ching Yun Hsieh Division of Hematology & Oncology
- Ming-Yu Lien 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
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, 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
注射劑
Active Ingredient
GSK5764227
Dosage Form
270
Dosage
100mg
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, irrespective of mutational status, 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 a life expectancy >12 weeks.
Has adequate organ function. Screening specimens must be collected at least 3-5 days prior to pre-dose specimens, and pre-dose specimens must be collected within 24 hours prior to first dose.
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) for all except ES-SCLC participants. Exemptions can be granted by the medical monitor for participants with bladder cancer and mCRPC. 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) are not contraindicated.
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)
Has received no more than 4 cycles of cisplatin or carboplatin in combination with pembrolizumab, atezolizumab, or durvalumab as most recent treatment regimen, with objective response (per RECIST 1.1) of SD or better and no PD, and otherwise qualifies for continued treatment with atezolizumab, durvalumab, or pembrolizumab per local practice guidelines (combination 2 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, irrespective of mutational status, 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 a life expectancy >12 weeks.
Has adequate organ function. Screening specimens must be collected at least 3-5 days prior to pre-dose specimens, and pre-dose specimens must be collected within 24 hours prior to first dose.
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) for all except ES-SCLC participants. Exemptions can be granted by the medical monitor for participants with bladder cancer and mCRPC. 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) are not contraindicated.
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)
Has received no more than 4 cycles of cisplatin or carboplatin in combination with pembrolizumab, atezolizumab, or durvalumab as most recent treatment regimen, with objective response (per RECIST 1.1) of SD or better and no PD, and otherwise qualifies for continued treatment with atezolizumab, durvalumab, or pembrolizumab per local practice guidelines (combination 2 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.
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 midline shift due to herniation); 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.
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, or intra-abdominal abscess.
History of bowel involvement on CT scan or clinical symptoms of 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.
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 midline shift due to herniation); 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.
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, or intra-abdominal abscess.
History of bowel involvement on CT scan or clinical symptoms of 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.
The Estimated Number of Participants
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Taiwan
15 participants
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Global
160 participants
