The goal of this clinical trial is to test a new medicine called GSK5764227, which delivers a toxin directly to cancer cells to destroy them while sparing healthy cells. The study will combine GSK5764227 with standard treatments to evaluate its safety, examine how the body processes it, check if it triggers any immune responses, and assess whether it can shrink or control cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
Participants will receive GSK5764227.
Participants will receive bevacizumab.
Participants will receive fluorouracil.
GSK Investigational Site
Lake Success, New York, United States
RECRUITINGGSK Investigational Site
Tugun, Queensland, Australia
RECRUITINGGSK Investigational Site
Barcelona, Spain
Number of participants with adverse events (AEs), Serious AEs (SAEs), AE of special interest (AESIs) and AEs leading to dose modifications
Time frame: Up to approximately 31 weeks
Number of participants with AEs, SAEs, AESIs, and AEs leading to dose modifications by severity
Time frame: Up to approximately 31 weeks
Number of participants with dose limiting toxicities (DLTs)
Time frame: Up to approximately 31 weeks
Number of participants with clinically significant changes in Vital Signs, Body Weight, Laboratory Tests [Hematology, Clinical Chemistry, Urinalysis], Cardiac Function [ECG], and Eastern Cooperative Oncology Group (ECOG) performance status
Time frame: Up to approximately 31 weeks
Plasma concentration of GSK5764227 [conjugated antibody and payload (GSK5757810)
Time frame: Up to approximately 112 weeks
Number of participants with anti-drug antibody (ADA) against GSK5764227
Time frame: Up to approximately 112 weeks
Number of participants with neutralising antibody (NAb) against GSK5764227
Time frame: Up to approximately 112 weeks
Titer of ADA against GSK5764227
Time frame: Up to approximately 112 weeks
Objective Response Rate (ORR)
ORR is defined as the proportion of participants who have achieved best observed response (BOR) of confirmed complete response (CR) or partial response (PR) as assessed by investigator, according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for Cohort A or per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) for Cohort B.
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Participants will receive leucovorin.
Participants will receive enzalutamide.
GSK Investigational Site
Madrid, Spain
RECRUITINGGSK Investigational Site
Madrid, Spain
RECRUITINGGSK Investigational Site
Málaga, Spain
RECRUITINGTime frame: Up to approximately 112 weeks
Disease control Rate (DCR18)
DCR18 is defined as the proportion of participants who have achieved CR or PR, or stable disease (SD) of ≥17 weeks as assessed by investigator according to PCWG3 for Cohort B.
Time frame: Up to approximately 112 weeks
Duration of Response (DoR)
DOR is defined as the time from the date of the first documented objective response (CR/PR) as assessed by investigator according to RECIST 1.1 for cohort A or PCWG3 for cohort B, until the date of the first documented disease progression (PD) or death due to any cause, whichever is earlier.
Time frame: Up to approximately 112 weeks
Progression free survival (PFS)
PFS is defined as the time from the date of first dose until the earliest date of documented disease progression as assessed by investigator according to RECIST 1.1 for cohort A.
Time frame: Up to approximately 112 weeks
Radiographic progression-free survival (rPFS)
rPFS is defined as the time from the date of first dose until the earliest date of documented PD per PCWG3-modified RECIST 1.1 (soft tissue lesion assessment) and/or PCWG3 bone lesion assessment for cohort B or death due to any cause.
Time frame: Up to approximately 112 weeks
Prostate-specific antigen 50 (PSA50)
PSA50 is defined as percentage of participants with a decrease of \>=50% in the PSA concentration from the baseline PSA value, confirmed at least 3 weeks later (cohort B)
Time frame: Up to approximately 112 weeks