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NCT Number: NCT07277270

A Study of GSK5764227 in Combination With Standard of Care (SoC) or Other Agents in Participants With Advanced Solid Tumors

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.

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site, Tugun, Queensland, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

GSK5764227

Drug

Participants will receive GSK5764227.

Bevacizumab

Drug

Participants will receive bevacizumab.

Fluorouracil

Drug

Participants will receive fluorouracil.

Leucovorin

Drug

Participants will receive leucovorin.

Enzalutamide

Drug

Participants will receive enzalutamide.

Primary outcomes

  1. 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

  2. Number of participants with AEs, SAEs, AESIs, and AEs leading to dose modifications by severity

    Time frame: Up to approximately 31 weeks

  3. Number of participants with dose limiting toxicities (DLTs)

    Time frame: Up to approximately 31 weeks

  4. 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

Secondary outcomes

  1. Plasma concentration of GSK5764227 [conjugated antibody and payload (GSK5757810)

    Time frame: Up to approximately 112 weeks

  2. Number of participants with anti-drug antibody (ADA) against GSK5764227

    Time frame: Up to approximately 112 weeks

  3. Number of participants with neutralising antibody (NAb) against GSK5764227

    Time frame: Up to approximately 112 weeks

  4. Titer of ADA against GSK5764227

    Time frame: Up to approximately 112 weeks

  5. Objective Response Rate (ORR)

    Time frame: 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.

  6. Disease control Rate (DCR18)

    Time frame: 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.

  7. Duration of Response (DoR)

    Time frame: 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.

  8. Progression free survival (PFS)

    Time frame: 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.

  9. Radiographic progression-free survival (rPFS)

    Time frame: 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.

  10. Prostate-specific antigen 50 (PSA50)

    Time frame: 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)

Study contacts

Contact information is provided by the study sponsor or research team.

EU GSK Clinical Trials Call Center

CONTACT

[email protected]

+44 (0) 20 89904466

US GSK Clinical Trials Call Center

CONTACT

[email protected]

877-379-3718

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

A Phase 1b/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5764227 in Combination With Standard of Care (SoC) or Other Agents in Participants With Advanced Solid Tumors

Important dates

Study start
2025
Primary completion
2026
Study completion
2028
First posted
Dec 11, 2025
Registry last updated
Jan 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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