In short
Clinical trials are studying GSK4418959A in people with dMMR/MSI-H solid tumors, including colorectal cancer. The trials are looking at safety, tolerability, dose selection, and early signs of anti-tumor activity. Some parts test GSK4418959A alone, and others test it with a PD-1 inhibitor.
Key points
- Clinical trials are studying GSK4418959A in people with dMMR/MSI-H solid tumors, with colorectal cancer clearly included and endometrial cancer mentioned in one part of the study. This is a Phase 1/2 trial, so it is designed to find a safe dose and look for early signs that the treatment may work. The study tests GSK4418959A alone and also with a PD-1 inhibitor. Researchers are measuring safety, dose-limiting toxicities, treatment-emergent side effects, dose changes, treatment stops, and tumor response. The trial status is Authorised and the planned enrollment is 69 people.
Trial overview
The main study is FTIH study, which means a first-time-in-humans study. It is designed to look at the safety and early efficacy of GSK4418959A, meaning whether the treatment may help shrink or control tumors.
This trial is for people with dMMR/MSI-H solid tumors, and colorectal cancer is specifically listed as a condition being studied. The study status is Authorised and the planned enrollment is 69 participants.
Who can participate
The trial focuses on people with solid tumors that have dMMR or MSI-H features, which are tumor traits related to DNA repair problems and many DNA changes.
Colorectal cancer is one of the main conditions named in the study, and the brief summary also says that one part of the trial separately looks at endometrial cancer. Endometrial cancer starts in the lining of the uterus.
What the studies are measuring
In the early dose-finding parts, researchers are measuring dose-limiting toxicities, which are side effects serious enough to stop a dose from being raised further.
They are also measuring treatment-emergent adverse events, which are health problems that begin or get worse after treatment starts.
Other safety measures include dose interruptions, dose reductions, and stopping treatment because of side effects.
For the tumor response part of the study, the main endpoint is overall response rate, which means the percentage of participants with a confirmed complete response or partial response based on RECIST 1.1 and investigator assessment.
Trial phases and study parts
This is a Phase 1/2 trial, so it combines early safety work with an early look at whether the treatment may help the cancer.
In Part 1, the study aims to find the maximum tolerated dose and/or the recommended dose for expansion for GSK4418959A used alone.
In Part 2, the study evaluates the preliminary anti-tumor activity of GSK4418959A in colorectal cancer and separately in endometrial cancer.
In Part 3, the study looks at GSK4418959A given with a PD-1 inhibitor, which is a type of cancer treatment that helps the immune system attack cancer cells.
Treatments being tested
The trial includes GSK4418959A given by oral use in more than one study part.
It also includes a combination arm with JEMPERLI, which is listed as a PD-1 inhibitor given by intravenous use.
The study is not just asking whether the treatment works. It is also asking whether the treatment can be given safely enough to choose a dose for later research.
What the results mean for patients
For patients, the most important question in this study is whether GSK4418959A can be given at a dose that is both tolerable and active against the cancer.
The study is still early, so it is mainly about learning rather than proving benefit. The results may help decide the best dose for future studies and show whether the treatment should be studied further in these cancers.