Neoplasms
Conditions
Keywords
Solid Tumors, Metastatic colorectal cancer, Metastatic castration-resistant prostate cancer, GSK5764227, Bevacizumab, Fluorouracil, Folinic acid, Enzalutamide, EMBOLD, EMBOLD PanTumor-102
Brief summary
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.
Interventions
DRUGGSK5764227
Participants will receive GSK5764227.
DRUGBevacizumab
Participants will receive bevacizumab.
DRUGFluorouracil
Participants will receive fluorouracil.
DRUGleucovorin
Participants will receive leucovorin.
DRUGEnzalutamide
Participants will receive enzalutamide.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose. * Has adequate organ function. * Has histologically confirmed unresectable adenocarcinoma or unresectable metastatic adenocarcinoma of the colon or rectum. (Cohort A) * Histologically or cytologically confirmed adenocarcinoma of the prostate (Cohort B)
Exclusion criteria
* Has a malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas \[e.g., breast, cervix, bladder\] that have been resected with no evidence of disease. * Has had any major surgery within 28 days prior to first dose. * Has clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose. * Has serious infection within 4 weeks prior to the first dose, * Has untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed * Any evidence of current interstitial lung disease (ILD) or pneumonitis OR a prior history of ILD requiring high-dose glucocorticoids or non-infectious pneumonitis requiring high-dose glucocorticoids. * Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening. * Has received immunosuppressive agents within 30 days prior to first dose of study intervention (or requires long-term \[30 days or longer\]). Low-dose corticosteroids (prednisone ≤10 milligrams (mg)/day or equivalent) may be administered.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with adverse events (AEs), Serious AEs (SAEs), AE of special interest (AESIs) and AEs leading to dose modifications | Up to approximately 31 weeks |
| Number of participants with AEs, SAEs, AESIs, and AEs leading to dose modifications by severity | Up to approximately 31 weeks |
| Number of participants with dose limiting toxicities (DLTs) | 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 | Up to approximately 31 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 112 weeks | 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. |
| Disease control Rate (DCR18) | Up to approximately 112 weeks | 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. |
| Duration of Response (DoR) | Up to approximately 112 weeks | 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. |
| Plasma concentration of GSK5764227 [conjugated antibody and payload (GSK5757810) | Up to approximately 112 weeks | — |
| Radiographic progression-free survival (rPFS) | Up to approximately 112 weeks | 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. |
| Prostate-specific antigen 50 (PSA50) | Up to approximately 112 weeks | 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) |
| Progression free survival (PFS) | Up to approximately 112 weeks | 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. |
| Number of participants with anti-drug antibody (ADA) against GSK5764227 | Up to approximately 112 weeks | — |
| Number of participants with neutralising antibody (NAb) against GSK5764227 | Up to approximately 112 weeks | — |
| Titer of ADA against GSK5764227 | Up to approximately 112 weeks | — |
Countries
Australia, Spain, United States
Contacts
Primary ContactUS GSK Clinical Trials Call Center
Backup ContactEU GSK Clinical Trials Call Center
Outcome results
None listed