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GSK5764227 for adults with advanced unresectable gastrointestinal cancers

A Phase 1b/2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of GSK5764227 Alone and in Combination in Participants With Previously Treated Advanced Unresectable or Metastatic Gastrointestinal Solid Tumors

PHASE1; PHASE2 · GlaxoSmithKline · NCT06885034

This test tries the drug GSK5764227, alone or with other treatments, in adults with advanced gastrointestinal cancers that cannot be removed by surgery and who have had prior therapy.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment320 (estimated)
Ages18 Years and up
SexAll
SponsorGlaxoSmithKline (industry)
Locations47 sites (Los Alamitos, California and 46 other locations)
Trial IDNCT06885034 on ClinicalTrials.gov

What this trial studies

This phase 1/2 study gives GSK5764227 alone or in combination to adults with unresectable or metastatic gastrointestinal cancers to measure safety, side effects, pharmacokinetics, and early signs of tumor response. The trial includes separate cohorts for colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC), with CRC patients having received 1–2 prior lines of systemic therapy and PDAC patients having received one prior systemic therapy. Participants must provide tumor tissue (fresh biopsy or archival) and will undergo regular imaging and laboratory monitoring to track response and how the drug is handled by the body. The study is conducted at selected GSK investigational sites and follows the typical early-phase dose-finding and expansion approach.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed unresectable or metastatic colorectal adenocarcinoma or pancreatic ductal adenocarcinoma who meet the protocol's prior-treatment limits, can provide required tumor tissue, and can attend study visits are eligible.

Not a fit: Patients with cancers that can still be removed surgically, those who exceed the allowed number of prior therapies, are medically ineligible for experimental treatment, or cannot travel to the study sites are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, GSK5764227 could provide a new treatment option that shrinks tumors or slows disease progression for people with advanced unresectable gastrointestinal cancers.

How similar studies have performed: Some targeted and experimental agents have produced meaningful responses in subsets of gastrointestinal cancers, but GSK5764227 itself is an experimental compound with limited prior human data.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

• Is at least 18 or the legal age of consent in the jurisdiction in which the study is taking place years of age at the time of signing the informed consent form (ICF).

CRC Cohort

* Has histologically confirmed unresectable/, locally advanced or unresectable metastatic adenocarcinoma of the colon or rectum (histology defined by World Health Organization (WHO) classification).
* Must have received at least 1 and no more than 2 lines of systemic treatment for advanced colorectal cancer (CRC), with documented progression on most recent prior line of therapy.
* Must provide tumor tissue from a newly obtained fresh biopsy or an archival tumor tissue.

PDAC Cohort

* Has histologically or cytologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the pancreas (histology defined by WHO classification).
* Must have received 1 and no more than 1 line of therapy for advanced PDAC, with documented progression.
* Should provide tumor tissue at screening, where available or medically feasible.

All Cohorts

* Has at least 1 target lesion per RECIST 1.1, as determined by the investigator.
* Is willing to use adequate contraception.
* Is capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the ICF and in the protocol.
* Has an ECOG performance status of 0 or 1.
* Has adequate organ function.

Exclusion criteria:

Participants are excluded from the study if any of the following criteria apply:

* 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 randomization (CRC Cohort) or first dose of study intervention (PDAC Cohort).
* Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
* Has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
* Has severe, uncontrolled or active cardiovascular disorders.
* Has serious or poorly controlled hypertension.
* 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.
* Known active infectious diseases requiring systemic treatment or known Human immunodeficiency virus (HIV).
* Has serious arteriovenous thromboembolic events (such as deep vein thrombosis, pulmonary embolism, etc.) within 3 months prior to the first dose.
* Has untreated brain or Central nervous system (CNS) metastases or brain/CNS metastases that have progressed.
* Has current active pneumonitis or any history of pneumonitis requiring steroids or immunomodulatory treatment within 90 days of planned \[randomization\] or any history of drug-induced pneumonitis.
* Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening.
* Has any active renal condition (e.g., infection, requirement for dialysis, or any other significant renal condition that could affect the participant's safety).
* Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to Grade 1 or to the baseline status preceding prior therapy.
* Has any serious and/or unstable medical or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant's safety, obtainment of informed consent, or compliance to the study procedures.
* Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
* Has documented presence of Hepatitis B surface antigen (HBsAg) or HBcAb at screening or within 3 months prior to the first dose of study intervention.
* Has a positive Hepatitis C virus (HCV) antibody test result at screening or within 3 months prior to the first dose of study intervention.
* Has a positive HCV RNA test result at screening or within 3 months prior to the first dose of study intervention.
* Has received immunosuppressive agents within 30 days prior to first dose of study intervention (or requires long-term \[30 days or longer\]).
* Has received any prior therapy with an Antibody-drug conjugate (ADC) with a Topoisomerase-1 (TOPO1)-inhibitor payload.
* Has received any live vaccine within 30 days of randomization (CRC Cohort) or before first dose of study intervention (PDAC Cohort).
* Is currently enrolled or has participated in any other clinical study involving an investigational study intervention or any other type of interventional medical research and/or has received treatment with any anticancer or investigational agent within 4 weeks prior to randomization.
* Is pregnant or breastfeeding.
* Is unable to adhere to the protocol defined SoA, including requirements for the Follow-up Period of the study.

Where this trial is running

Los Alamitos, California and 46 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Gastrointestinal Neoplasms, GSK5764227, Solid Tumors, Colorectal Cancer, Pancreatic ductal adenocarcinoma

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.