Study of GSK5733584 versus paclitaxel or doxorubicin in patients with advanced or recurrent endometrial cancer after platinum‑based chemotherapy and immunotherapy
The study focuses on endometrial cancer, a type of cancer that starts in the lining of the uterus. It evaluates a new medicine called mocertatug rezetecan given by intravenous infusion (a drip into a vein) and compares it with standard chemotherapy drugs, specifically doxorubicin and paclitaxel. The aim is to see whether the new medicine works better at shrinking tumors and delaying disease spread after patients have already received platinum‑based chemotherapy and immunotherapy, which are other common cancer treatments.
Participants are randomly assigned to receive either the new drug or one of the standard chemotherapy options. Treatment cycles are given every few weeks, and participants return for regular check‑ups that include scans to look for changes in tumor size, blood tests, and questionnaires about quality of life. The study follows each participant for several months to track how long the disease stays under control, overall survival, and any side effects that may occur.
1randomization
after enrollment, you will be assigned by a computer system to one of two groups: the Mo-Rez group or the chemotherapy group. the assignment is random and cannot be predicted.
2baseline assessments
before the first infusion, a series of tests will be performed to record your current health status. these include a physical examination, blood tests, electrocardiogram (ecg, a test that records the electrical activity of the heart), and imaging studies such as scans to measure the size of the tumor.
questionnaires about your quality of life and symptoms will also be completed.
3first infusion of assigned medication
you will receive an intravenous infusion (a medicine delivered through a vein) of the medication assigned to you.
if you are in the Mo-Rez group, the dose is 5.8 mg per kilogram of body weight, supplied as a powder that is mixed for infusion.
if you are in the chemotherapy group, the physician will choose either:
– paclitaxel at a dose of 80 mg per square meter of body surface area, given as a solution for infusion, or
– doxorubicin at a dose of 60 mg per square meter of body surface area, given as a solution for infusion.
the exact schedule (how often the infusion is given) follows the study protocol and will be explained by the study team.
4treatment cycles
the assigned medication will be administered repeatedly in cycles according to the protocol. each cycle ends with a short observation period before the next infusion.
treatment continues until disease progression, unacceptable side effects, or completion of the planned number of cycles.
5regular monitoring
at each visit you will have vital signs checked (blood pressure, pulse, temperature), blood drawn for laboratory tests, and an ecg performed.
the study staff will ask about any new or worsening symptoms and record any adverse events (side effects).
6imaging assessments
periodically, imaging scans will be repeated to evaluate tumor size. the response is measured using the RECIST 1.1 criteria, a standardized method to determine if the tumor has shrunk, stayed the same, or grown.
7quality‑of‑life questionnaires
you will complete standardized questionnaires (such as the eortc qlq‑c30 and eortc qlq‑en24) at defined time points to assess physical functioning, pain, and other symptoms.
8dose adjustments
if laboratory results or side effects reach predefined limits, the study protocol may require a temporary delay of the next infusion or a reduction in the dose.
any changes will be documented and explained to you.
9end‑of‑treatment assessment
when treatment stops, a final set of assessments will be performed, including imaging, laboratory tests, and quality‑of‑life questionnaires, to document the overall outcome.
10follow‑up visits
after treatment ends, you will continue to be seen at scheduled intervals to monitor overall survival and long‑term safety. these visits may include blood tests, imaging, and symptom questionnaires.
Who Can Join the Study?
Has a diagnosis of endometrial cancer that was confirmed by looking at tumor tissue under a microscope (called a histology test). This includes several sub‑types such as endometrioid, serous, clear cell, carcinosarcoma, or mixed epithelial cancers.
Has received at least 1 but no more than 2 separate courses (called “lines”) of chemotherapy for endometrial cancer. Up to 3 lines are allowed if one of those courses was given as extra treatment after surgery (known as adjuvant or neo‑adjuvant therapy). Switching medicines within the same drug class because of side effects does not count as a new line, and hormonal therapy is not counted as a separate line.
Must have disease that got worse after earlier platinum‑based chemotherapy and after receiving a medicine that blocks the PD‑1/PD‑L1 pathway (a type of immunotherapy). Even if they could not take a PD‑1/PD‑L1 drug because of immune‑system problems, they are still eligible.
If the only prior platinum chemotherapy was given after surgery, the time since the last platinum dose (called the platinum‑free interval) must be less than 12 months. This rule does not apply if a PD‑1/PD‑L1 drug was given together with platinum, if the cancer has spread (metastatic), or if the patient cannot tolerate platinum.
Must provide a preserved tumor tissue sample (called FFPE – formalin‑fixed, paraffin‑embedded) that can be tested for the protein B7‑H4. The test result must be available before the patient is randomly assigned to a treatment group.
Must have at least one tumor spot that can be measured according to the standard criteria called RECIST 1.1, which is used to track how tumors change in size.
Must have an overall health rating of 0 or 1 on the ECOG performance status scale, meaning the person is fully active (0) or able to do light work (1).
Must have adequate organ function, which means laboratory tests show:
White blood cells (ANC) ≥ 1,500 per microliter
Platelet count ≥ 100,000 per microliter
Hemoglobin (a measure of red blood cells) ≥ 9.0 g/dL
Kidney function (eGFR) ≥ 30 mL/min
Blood albumin (a protein) ≥ 2.5 g/dL
Blood clotting tests (INR/PT or aPTT) within normal limits unless the person is taking blood thinners, in which case the results must be in the therapeutic range.
Must be an adult (generally 18 years of age or older) and can be either male or female.
Who Cannot Join the Study?
You cannot join the study if you have a type of uterine cancer called a mesenchymal tumor (also known as uterine sarcoma) or a neuroendocrine uterine cancer.
You cannot join the study if you have another cancer (besides the endometrial cancer being studied) that has gotten worse or needed treatment in the past 3 years, except for certain skin cancers that have been completely removed.
You cannot join the study if you have ever had a bone‑marrow transplant or a solid‑organ transplant (for example, a kidney or liver transplant).
You cannot join the study if you currently have, or have previously had, interstitial lung disease (ILD) or pneumonitis (a type of lung inflammation).
You cannot join the study if you had a major surgery within the last 28 days, or if you received local radiation therapy within the last 21 days.
You cannot join the study if you took part in another experimental drug study within the last 30 days.
You cannot join the study if you have previously been treated with Topo1 inhibitors (such as irinotecan or topotecan) or with antibody‑drug conjugates that contain a Topo1 inhibitor, or with B7‑H4‑targeted therapy.
You cannot join the study if you received any chemotherapy, hormone therapy, targeted therapy, immunotherapy, or other anti‑cancer drugs within the last 30 days (or within five drug half‑lives), or if you need to keep taking these drugs during the study.
You cannot join the study if you received a live vaccine (such as measles, mumps, or rubella) within the last 30 days. (COVID‑19 mRNA or adenoviral vaccines are not considered live.)
You cannot join the study if you have taken medicines that affect certain drug‑transport proteins (P‑gp, BCRP, or OATP1B1/1B3) within 7 days before the first dose, or if you have taken medicines that increase P‑gp activity within the last 14 days.
You cannot join the study if you received a blood transfusion (red cells or platelets) or drugs that stimulate blood‑cell production (such as G‑CSF, GM‑CSF, or erythropoietin) within the last 14 days.
You cannot join the study if your liver enzyme ALT is more than 2.5 times the normal upper limit (ULN), or more than 5 times if you have liver metastases.
You cannot join the study if your total bilirubin level is more than 1.5 times the normal upper limit.
You cannot join the study if you have cirrhosis or an unstable liver or bile‑duct disease, such as fluid in the abdomen (ascites), brain confusion (encephalopathy), abnormal clotting (coagulopathy), low blood protein (hypoalbuminemia), enlarged veins in the esophagus or stomach (varices), or ongoing yellowing of the skin (jaundice).
You cannot join the study if you test positive for HBsAg or HBcAb (markers of hepatitis B infection) at screening.
You cannot join the study if you test positive for a hepatitis C antibody within the last 3 months unless a follow‑up test shows no active virus (negative HCV RNA).
You cannot join the study if you have a positive HCV RNA test (indicating active hepatitis C infection) at screening or within the last 3 months.
You cannot join the study if your heart’s electrical measurement QTc is longer than 470 milliseconds.
You cannot join the study if you have had a serious or uncontrolled heart problem in the past year, such as a heart attack, severe heart failure (NYHA Class III or IV), or a dangerous heart rhythm that is not controlled.
If the doctor plans to give you doxorubicin, you cannot join the study if your heart’s pumping ability (LVEF, left ventricular ejection fraction) is less than 50% or below the lab’s normal range.
You cannot join the study if you have an active kidney problem, such as an infection, need for dialysis, or any other serious kidney condition that could affect your safety (except a kidney blockage that has already been treated).
Paclitaxel is a chemotherapy medicine that is given through an IV. In this study it is used as one of the standard treatments that doctors may choose instead of the new drug. It works by stopping cancer cells from dividing and growing, helping to shrink or control the tumor.
Doxorubicin is another chemotherapy drug given by IV. It is also offered as a standard option for participants in the trial. Doxorubicin attacks cancer cells by interfering with their DNA, which can slow or stop the cancer from spreading.
GSK5733584 is the experimental medicine being tested in the trial (also called Mo‑Rez). It is supplied as a powder that is mixed with liquid and given through an IV. The drug is being studied to see if it works better or safer than the usual chemotherapy options for people with advanced or recurrent endometrial cancer.
Endometrial cancer – Endometrial cancer originates in the lining of the uterus and often causes abnormal uterine bleeding. The tumor can grow outward to involve the cervix, myometrium, and surrounding pelvic tissues. Cancer cells may travel through lymphatic vessels to nearby lymph nodes and further into the abdomen. When the disease spreads beyond the uterus it is considered advanced, and if it reappears after initial treatment it is termed recurrent. Over time, the cancer can reach distant organs such as the lungs or liver.
The website uses cookies to ensure the proper functioning of the site and to analyze internet traffic. Some cookies are essential for using the service and do not require consent. You can accept all cookies or use only the essential ones. Data is processed in accordance with our Privacy Policy. You have the right to withdraw your consent, access, rectify, delete, or limit the processing of your data at any time.
Belgium 
Czechia 
Denmark 
Germany 
Greece 
Italy 
Norway 
Poland 
Portugal 
Spain 
The Netherlands 
