Efficacy and Safety Evaluation of GSK5764227 Monotherapy and Combination Therapy in Advanced Unresectable or Metastatic Gastrointestinal Neoplasms

The primary objective of this study is to evaluate the clinical efficacy of two doses of **GSK5764227** in participants with metastatic colorectal cancer (mCRC) who have previously been treated for advanced unresectable or metastatic **gastrointestinal neoplasms**. This evaluation is crucial as it aims to determine the potential therapeutic benefits of GSK5764227, which could provide an alternative treatment option for patients with limited choices due to the advanced stage of their disease.

The clinical trial involves a total of **45 participants** diagnosed with **gastrointestinal neoplasms**, specifically metastatic colorectal cancer (mCRC). The study population includes both male and female subjects, aged 18 years and older, who have histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum. Participants have previously undergone 1-2 lines of systemic treatment for advanced colorectal cancer, including a fluoropyrimidine, oxaliplatin and/or irinotecan, and an anti-VEGF or anti-EGFR monoclonal antibody, if available. The trial population was selected based on specific inclusion criteria, such as having at least one target lesion per RECIST 1.1, providing tumor tissue from a fresh biopsy or archival source, and maintaining an ECOG performance status of 0 or 1 without deterioration in the two weeks prior to randomization. Participants are required to have adequate organ function and are not part of a vulnerable population. Lifestyle factors such as diet and physical activity are not specified in the trial data provided.

The clinical trial is a **phase 1b/2**, multicenter, randomized, open-label study designed to evaluate the efficacy and safety of **GSK5764227** alone and in combination in participants with previously treated advanced unresectable or metastatic **gastrointestinal neoplasms**. The trial is set to commence recruitment on August 15, 2025, and is estimated to conclude by March 9, 2028. Participants will be randomly assigned to receive different doses of the investigational product, which is administered as a **powder for solution for infusion** via **intravenous use**. The primary endpoint is the confirmed objective response rate (ORR), defined as the proportion of participants achieving a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST 1.1 criteria.

The study will include several key visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as age, histologically confirmed diagnosis, prior treatment history, and adequate organ function. Participants must provide tumor tissue from a newly obtained biopsy or archival tissue. Following the screening, participants will undergo regular follow-up visits to monitor safety, efficacy, and any adverse events. The end-of-study visit will occur after the final treatment cycle to assess the overall outcomes and gather final data.

Participant involvement is expected to last until the end of the study, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial is not classified as low intervention, and it integrates both phase I and phase II components to comprehensively assess the investigational product's clinical efficacy and safety profile in the target population.

The clinical trial involves the administration of **GSK5764227**, an experimental medication developed by GlaxoSmithKline Research & Development Limited. This investigational product is formulated as a **powder for solution for infusion**. The active substance, GSK5764227, is classified as a protein of other origin. The medication is administered via the **intravenous route**. The study is designed to evaluate the efficacy and safety of GSK5764227 in participants with previously treated advanced unresectable or metastatic gastrointestinal solid tumors. The trial includes a phase 1b/2, multicenter, randomized, open-label study format. The dosing schedule and frequency of administration are determined based on the specific cohort and phase of the trial, with compliance monitored throughout the study duration.

In this trial, GSK5764227 is administered alone and in combination with other treatments, as specified in the study protocol. The trial does not include a placebo or comparator treatment, focusing solely on the investigational product's effects. Participants' adherence to the dosing regimen is closely monitored to ensure accurate assessment of the medication's efficacy and safety. The study aims to provide valuable insights into the potential therapeutic benefits of GSK5764227 for patients with metastatic colorectal cancer (mCRC) and other gastrointestinal solid tumors.

The efficacy of the investigational product GSK5764227 in the clinical trial will be assessed primarily through the **Objective Response Rate (ORR)**. This is defined as the proportion of participants who achieve a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), as evaluated by the investigator according to the RECIST 1.1 criteria. The trial is designed to evaluate the clinical efficacy of two doses of GSK5764227 in participants with previously treated advanced unresectable or metastatic colorectal cancer (mCRC).