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

GlaxoSmithKline1 site in 1 country385 target enrollmentJuly 2, 2024

ConditionsSolid Tumors Neoplasms

InterventionsGSK5733584

DrugsGSK5733584

Overview

Phase: Phase 1
Intervention: GSK5733584
Conditions: Solid Tumors
Sponsor: GlaxoSmithKline
Enrollment: 385
Locations: 1
Primary Endpoint: Part 1: Number of participants with dose limiting toxicity (DLT)
Status: Recruiting
Last Updated: 10 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

July 2, 2024

End Date

September 20, 2027

Last Updated

10 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

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).
•PROC cohort
•Histologically documented, advanced (metastatic and/or unresectable) high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer.
•Must have received or are intolerant to 1 but no more than 3 lines of prior systemic therapy.
•Platinum-resistant disease, defined as progression or relapse within 6 months after the completion of platinum-based therapy.
•Must have had prior bevacizumab if the participant was considered a candidate for this regimen and the regimen is locally available.
•Participants with known Folate receptor-α (FR-α) expressing tumors must have received mirvetuximab soravtasine if the participants was considered a candidate for this regimen and the regimen is locally available.
•Participants with known Breast cancer susceptibility gene (BRCA) mutated tumors should have received a Poly adenosine diphosphate-ribose polymerase (PARP) inhibitor if the participant was considered a candidate for this regimen and the regimen is locally available.
•Endometrial cancer cohort

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 28 days 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,

Arms & Interventions

Part 1: Dose Escalation

Participants with advanced solid tumors who are refractory or intolerant to established standard therapies

Intervention: GSK5733584

Part 2: Dose Expansion

Participants with platinum-resistant ovarian cancer (PROC) and endometrial cancer (EC)

Intervention: GSK5733584

Outcomes

Primary Outcomes

Part 1: Number of participants with dose limiting toxicity (DLT)

Time Frame: Up to 21 days

Part 2: Confirmed Objective Response Rate (ORR)

Time Frame: Up to approximately 28 months

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)

Secondary Outcomes

Part 1 and 2: Maximum observed concentration (Cmax) of GSK5733584 and its components: conjugated antibody, total antibody, and small molecule toxin(Up to approximately 31 months)
Part 1 and 2: Time to reach Cmax (Tmax) of GSK5733584 and its components: conjugated antibody, total antibody, and small molecule toxin(Up to approximately 31 months)
Part 1 and 2: Area under the concentration-time curve (AUC) of GSK5733584 and its components: conjugated antibody, total antibody, and small molecule toxin(Up to approximately 31 months)
Part 1: Confirmed Objective Response Rate (ORR)(Up to approximately 31 months)
Part 1 and 2: Duration of response (DoR)(Up to approximately 31 months)
Part 1 and 2: Progression-free survival (PFS)(Up to approximately 31 months)
Part 1 and 2:Number of participants with treatment-emergent Anti-drug antibodies (ADA)/ Neutralizing antibody (NAb)(Up to approximately 31 months)
Part 1 and 2: Titers of ADA to GSK5733584(Up to approximately 31 months)
Part 1 and 2: Number of participants with Adverse Events (AEs), and Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)(Up to approximately 31 months)
Part 1 and 2: Change from baseline in body temperature (degree Celsius)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in respiratory rate (breaths per minute)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in pulse rate (beats per minute)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in blood pressure [millimetres of mercury (mmHg)](Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in weight [kilogram (kg)](Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in white blood cell count (cells per microliter)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in hemoglobin (grams per deciliter)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from Baseline in Platelet count (cells per microliter)(Baseline (Day -1) and up to approximately 31 months)
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)
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)
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)
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)
Part 1 and 2: Change from Baseline in AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per litre)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in Total Protein and Albumin (Grams per deciliter)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in Amylase and Lipase (Units per liter)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in Estimated glomerular filtration rate (eGFR) (milliliter per minute)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in Prothrombin Time (PT), Partial thromboplastin time (PTT) or Activated Partial Thromboplastin Time (aPTT) (seconds)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in liver panel parameter: International Normalized Ratio (INR)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in routine urine tests: Leukocyte esterase(Baseline (Day -1) and up to approximately 31 months)
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)
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)
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)
Part 1 and 2: Change From Baseline in routine urine tests: Specific Gravity (Ratio)(Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in CA-125 tumor marker among ovarian cancer participants [units per milliliter (U/mL)](Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in Thyroid stimulating hormone (TSH) [microunits per milliliter (µU/mL)](Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in free thyroxine (T4) [nanograms per deciliter (ng/dL)](Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in Electrocardiogram (ECG) readings [milliseconds (msec)](Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in Left ventricular ejection fraction (LVEF) [Percentage](Baseline (Day -1) and up to approximately 31 months)
Part 1 and 2: Change from baseline in Eastern Cooperative Oncology Group Performance Scale (ECOG PS) score(Baseline (Day -1) and up to approximately 31 months)
Part 2: Overall Survival (OS)(Up to approximately 31 months)