A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 for Injection in Participants With Advanced Solid Tumors

Solid Tumors Clinical Trial

Official title:

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 for Injection in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06431594
• Other study ID #: 222730
• Secondary ID: 2024-513860-25
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 21, 2024
• Est. completion date: January 21, 2027

Study information

• Verified date: June 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to assess the safety and tolerability of GSK5733584. The study will also see how the levels of GSK5733584 change over time at different dose amount.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 240
• Est. completion date: January 21, 2027
• Est. primary completion date: October 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• GSK5733584
GSK5733584 will be administered

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Blacktown	New South Wales
Australia	GSK Investigational Site	Sydney	New South Wales
Canada	GSK Investigational Site	Montréal	Quebec
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Finland	GSK Investigational Site	Helsinki
Netherlands	GSK Investigational Site	Amsterdam
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Lake Mary	Florida
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of participants with dose limiting toxicity (DLT)		Up to 21 days
Primary	Part 2: Objective Response Rate (ORR)	ORR is defined as the proportion of participants with at least one confirmed Complete Response (CR) or Partial Response (PR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	Up to approximately 28 months
Secondary	Part 1 and 2: Maximum observed concentration (Cmax) of GSK5733584		Up to approximately 31 months
Secondary	Part 1 and 2: Time to reach Cmax (Tmax) of GSK5733584		Up to approximately 31 months
Secondary	Part 1 and 2: Area under the concentration-time curve (AUC) of GSK5733584		Up to approximately 31 months
Secondary	Part 1: Objective Response Rate (ORR)	ORR is defined as the proportion of participants with at least one confirmed CR or PR as defined by RECIST 1.1	Up to approximately 31 months
Secondary	Part 1 and 2: Disease control rate (DCR)	DCR is defined as the percentage of subjects whose best overall response is Complete Response (CR), Partial Response (PR) or Stable Disease (SD)	Up to approximately 31 months
Secondary	Part 1 and 2: Duration of response (DoR)	DoR is defined as the time interval between the date of the first documented response (CR or PR) and the date of the first documented disease progression or death due to any cause	Up to approximately 31 months
Secondary	Part 1 and 2: Progression-free survival (PFS)	PFS is defined as the time interval between randomization (or from the first dose of the intervention) and the first documented disease progression or death due to any cause (whichever occurs first).	Up to approximately 31 months
Secondary	Part 1 and 2:Number of participants with treatment-emergent Anti-drug antibodies (ADA)		Up to approximately 31 months
Secondary	Part 1 and 2: Titers of ADA to GSK5733584		Up to approximately 31 months
Secondary	Part 1 and 2: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to approximately 31 months
Secondary	Part 1 and 2: Number of participants with clinically significant changes in physical examination		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in body temperature (degree Celsius)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in respiratory rate (breaths per minute)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in pulse rate (beats per minute)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in blood pressure [millimetres of mercury (mmHg)]		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in weight [kilogram (kg)]		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in white blood cell count (cells per microliter)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in hemoglobin (grams per deciliter)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from Baseline in Platelet count (cells per microliter)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from Baseline in Red Blood Cell Count (RBC) (million cells per microliter)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from Baseline in haematocrit (Proportion of red blood cells in blood)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from Baseline in Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per litre)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from Baseline in Glucose (fasting), Blood Urea Nitrogen (BUN), Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium Direct Bilirubin and Total Bilirubin (milligrams per decilitre)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from Baseline in AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per litre)	Aspartate Aminotransferase (AST) / Serum Glutamic-Oxaloacetic Transaminase (SGOT), Alanine Aminotransferase (ALT)/ Serum Glutamic-Pyruvic Transaminase and (SGPT), Alkaline phosphatase (ALP) and Creatinine Phosphokinase (CPK) will be analysed	Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in Total Protein and Albumin (Grams per deciliter)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in Amylase and Lipase (Units per liter)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in Creatinine clearance (milliliter per minute)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in Activated Partial Thromboplastin Time (aPTT), Prothrombin Time (PT) and Thrombin time (seconds)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in fibrinogen (milligrams per deciliter)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in liver panel parameter: International Normalized Ratio (INR)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in routine urine tests: Leukocyte esterase	Leukocyte esterase measured as negative or positive	Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in routine urine tests: Occult blood (10^9 Cells Per Liter)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in routine urine tests: potential of hydrogen (pH) value		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in routine urine tests: Protein and bilirubin (Grams Per Liter)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change From Baseline in routine urine tests: Specific Gravity (Ratio)		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in CA-125 tumor marker [units per milliliter (U/mL)]		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in Electrocardiogram (ECG) readings [milliseconds (msec)]		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in Left ventricular ejection fraction (LVEF) [Percentage]		Baseline (Day -1) and up to approximately 31 months
Secondary	Part 1 and 2: Change from baseline in Eastern Cooperative Oncology Group Performance Scale (ECOG PS) score	ECOG PS is used for measuring how the disease impacts a patient's daily living abilities. The grades for the scale range from 0 (fully active) to 5 (dead), with increasing severity.	Baseline (Day -1) and up to approximately 31 months
Secondary	Part 2: Overall Survival (OS)	OS is defined as the time interval between the date of randomization (or from the first dose of the investigational product) and the date of death due to any cause	Up to approximately 31 months