A Study of GSK5764227 in Participants With Advanced Solid Tumors
NCT Number: NCT06551142
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Neoplasms
Interventions: DRUG: GSK5764227|DRUG: Topotecan
Sponsor: GlaxoSmithKline
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 260
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-30
Completion Date: 2027-06-09
Locations: GSK Investigational Site, Denver, Colorado, 80218, United States|GSK Investigational Site, New Haven, Connecticut, 06511, United States|GSK Investigational Site, Detroit, Michigan, 48201, United States|GSK Investigational Site, Nashville, Tennessee, 37203, United States|GSK Investigational Site, Dallas, Texas, 75230, United States|GSK Investigational Site, San Antonio, Texas, 78229, United States|GSK Investigational Site, Rosario, S2002, Argentina|GSK Investigational Site, Viedma, R8500ACE, Argentina|GSK Investigational Site, Montreal, H4A 3J1, Canada|GSK Investigational Site, Ottawa, K1H 8L6, Canada|GSK Investigational Site, Sherbrooke, J1H 5N4, Canada|GSK Investigational Site, Toronto, M5G 1X6, Canada|GSK Investigational Site, Bordeaux, 33076, France|GSK Investigational Site, Lyon cedex 08, 69373, France|GSK Investigational Site, Milano, 20141, Italy|GSK Investigational Site, Napoli, 80131, Italy|GSK Investigational Site, Roma, 00168, Italy|GSK Investigational Site, Chiba, 277-8577, Japan|GSK Investigational Site, Tokyo, 104-0045, Japan|GSK Investigational Site, Madrid, 28034, Spain|GSK Investigational Site, Madrid, 28040, Spain|GSK Investigational Site, Edinburgh, EH4 2XU, United Kingdom|GSK Investigational Site, Glasgow, G12 0YN, United Kingdom

Summary:
The goal of this study is to assess the safety, tolerability, clinical activity and pharmacokinetics of GSK5764227. The study will also see how the levels of GSK5764227 change over time at different dose amounts.

Primary Outcome Measures: Phase 1a: Number of participants with Adverse Events (AEs), 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 AEs leading to dose modifications, Up to approximately 28 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: Progression-free survival (PFS), 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, Up to approximately 27 months|Phase 1b: Objective Response Rate (ORR), 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, Up to approximately 27 months
Secondary Outcome Measures: Phase 1a and Phase 1b: Maximum concentration (Cmax) of GSK5764227, Up to approximately 28 months|Phase 1a and Phase 1b: Time to reach maximum concentration (Tmax) of GSK5764227, Up to approximately 28 months|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 (conjugated antibody), Up to approximately 28 months|Phase 1a and Phase 1b: Trough concentration (Ctrough) of GSK5764227 (total antibody), Up to approximately 28 months|Phase 1a and Phase 1b: Trough concentration (Ctrough) of GSK5764227 (small-molecule toxin), Up to approximately 28 months|Phase 1a: Objective Response Rate, ORR is defined as the proportion of participants who have confirmed CR or PR, assessed by the investigator according to RECIST V1.1 criteria, Up to approximately 33 months|Phase 1a and Phase 1b: Disease control rate (DCR), 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., Up to approximately 33 months|Phase 1a and Phase 1b: Duration of Response (DoR), DoR is defined as the time from first documented response (CR/PR) until the time of first documentation of disease progression, Up to approximately 33 months|Phase 1a and Phase 1b: Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb), Up to approximately 30 months|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 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), OS is defined as survival from the date of randomization to the date of death by any cause., Up to approximately 33 months|Phase 1b: Progression-Free Survival (PFS), 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, Up to approximately 33 months