A Phase 3 Study of GSK5733584 with drug combination in patients with platinum‑resistant ovarian cancer

3 1 1 1

What is this study about?

The study focuses on ovarian cancer that no longer responds to platinum‑based chemotherapy, a condition known as platinum‑resistant. Participants will receive either the investigational drug mocertatug rezetecan (also called Mo‑Rez) given by infusion, or a physician‑chosen standard therapy selected from a group of commonly used medicines such as topotecan, paclitaxel, pembrolizumab, doxorubicin, gemcitabine and bevacizumab.

The purpose of the trial is to evaluate the clinical efficacy of Mo‑Rez compared with the physician’s choice of standard of care in participants with platinum‑resistant ovarian cancer.

After giving informed consent, participants are randomly assigned—meaning by chance—to one of the two treatment groups. The assigned medication is administered through an intravenous line on a regular schedule. Throughout the study, participants attend clinic visits for safety checks, blood tests, and imaging scans (pictures of the inside of the body) to monitor tumor changes. They also complete questionnaires that assess symptoms and overall quality of life. The study continues until a predefined end point is reached or the participant and physician decide to stop treatment.

1 randomization

after you join the study, you are assigned a study number and the computer randomly places you into one of two groups.

one group receives the investigational drug gsk5733584 (dose: 5.8 mg per kilogram of body weight, given by intravenous infusion).

the other group receives the physician’s choice of a standard treatment, which may be one of the following intravenous drugs:

topotecan – 4 mg per square meter,

paclitaxel – 80 mg per square meter,

pembrolizumab (keytruda) – 400 mg,

doxorubicin (caelyx) – 40 mg per square meter,

gemcitabine – 1000 mg per square meter,

bevacizumab (zirabev) – 10 mg per kilogram.

2 baseline assessments

before the first infusion, you undergo a series of tests to document your health status.

these include physical measurements, blood laboratory tests, electrocardiogram (ecg), and imaging scans to evaluate the extent of ovarian cancer.

questionnaires about quality of life and symptoms are also completed.

3 first infusion

on the day of the first treatment, the assigned medication is prepared and administered through an intravenous line.

the infusion is performed in a clinical setting under medical supervision.

the dose described in the randomization step is given during this session.

4 subsequent infusions

you return for additional infusion visits according to the schedule determined by the study protocol.

at each visit, the same medication and the same dose (based on body surface area or weight) are administered.

the interval between infusions is consistent with standard practice for the selected drug, but exact timing follows the trial’s predefined schedule.

5 safety monitoring

before and after each infusion, vital signs (blood pressure, pulse, temperature) are checked.

blood samples are taken to monitor laboratory values such as blood counts and chemistry.

any side effects are recorded using patient‑reported questionnaires and clinical assessments.

6 disease evaluation

periodic imaging scans are performed to assess tumor size and determine whether the disease is progressing.

the same criteria (recist 1.1) are used throughout the study to ensure consistent evaluation.

7 dose adjustment

if side effects reach a level that requires a change, the study physician may delay the next infusion or reduce the dose.

any modification follows the predefined rules of the trial protocol.

8 treatment discontinuation

treatment stops when any of the following occurs: disease progression confirmed by imaging, unacceptable toxicity, withdrawal from the study, or completion of the planned number of cycles.

9 follow‑up

after treatment ends, you continue to be seen at scheduled intervals for safety checks and survival monitoring.

blood tests, imaging, and quality‑of‑life questionnaires are repeated to collect long‑term data.

Who Can Join the Study?

  • Age: You must be at least 18 years old and able to give legal consent for the study.
  • Organ function: Your blood and kidney tests must be normal enough, including white blood cells (ANC ≥ 1500 per microliter), platelets (≥ 100,000 per microliter), hemoglobin (≥ 9.0 g/dL), kidney filtration rate (eGFR ≥ 30 mL/min), blood protein albumin (≥ 2.5 g/dL), and clotting tests (INR/PT/aPTT) that are within safe limits, especially if you are not on blood‑thinning medication.
  • Epithelial ovarian cancer (or related cancers of the lining of the abdomen or fallopian tubes) that is confirmed by a tissue test to be one of the following types—high‑grade serous, high‑grade endometrioid, clear‑cell, or carcinosarcoma—and that no longer responds to platinum‑based chemotherapy (meaning the cancer grew back within 3‑6 months after the last platinum dose).
  • Previous cancer treatments: You must have had at least 1 but no more than 4 earlier rounds of systemic (whole‑body) anti‑cancer therapy. Different types of treatment are counted as one “line” unless a new drug from a different class was added.
  • Required prior drugs: You should have already received the following medicines unless you have a medical reason not to:
    • Mirvetuximab (if your tumor shows strong FRα protein on the cells),
    • Bevacizumab (unless you have conditions like uncontrolled high blood pressure, recent bleeding, or certain wound‑healing problems),
    • PARP inhibitor (PARPi) if you have a harmful BRCA gene mutation and responded to platinum chemotherapy.
  • Measurable tumor lesion: You need to have at least one tumor spot that can be measured on scans according to the RECIST 1.1 criteria (a standard way doctors define tumor size and changes).
  • Tumor tissue sample: You must provide a formalin‑fixed, paraffin‑embedded (FFPE) tumor sample that is large enough for the lab to test for three markers—B7‑H4, FRα, and PD‑L1. The sample should come from a recent, non‑irradiated site and cannot be a fine‑needle aspirate or bone marrow sample.
  • Contraception and pregnancy: You must be a female who is not pregnant or breastfeeding. You need to use a highly effective birth‑control method (failure rate < 1 % per year) starting at least 30 days before the first study dose, continue during the study, and keep using it for at least 8 months after the last dose. You also agree not to donate eggs during this time.
  • Pregnancy test: A very sensitive urine or blood pregnancy test must be negative within 24 hours before the first dose of the study drug.
  • ECOG performance status: Your overall daily activity level must be good, scored as 0 (fully active) or 1 (restricted in physically strenuous activity but ambulatory).

Who Cannot Join the Study?

  • Has primary platinum‑refractory ovarian cancer, meaning the cancer did not respond to or got worse within 3 months after the first round of platinum‑based chemotherapy.
  • For patients who would receive bevacizumab as part of the physician’s choice regimen: has a history of serious blood‑vessel problems (such as uncontrolled high blood pressure or blood clots), abnormal connections (fistula), bowel problems (rectosigmoid involvement or bowel blockage), poor wound healing, bleeding disorders (coughing up blood, nosebleeds, lung bleeding, or problems with blood clotting), kidney disease with large protein loss (nephrotic syndrome) or significant protein in urine, jaw bone loss (osteonecrosis of the jaw), or known allergy to the medication.
  • Had any major surgery within 28 days before the first study dose or received focused radiation therapy within 21 days before the first dose.
  • Received any experimental drug within 30 days before the first dose.
  • Received any chemotherapy, hormone therapy, targeted therapy, immunotherapy, biologic therapy, or other anti‑cancer drug within 30 days (or within five drug half‑lives, whichever is shorter) before the first dose, or needs to keep taking those drugs during the study.
  • Previously treated with topoisomerase I inhibitors (e.g., topotecan) or antibody‑drug conjugates that contain a TOP1 inhibitor, or with therapy that targets B7‑H4.
  • Received any live vaccine within 30 days before the first dose.
  • Taken drugs that block the transport proteins P‑gp, BCRP, or OATP1B1/1B3 within 7 days before the first dose (P‑gp inducers must be stopped at least 14 days before the first dose).
  • Received a blood transfusion (red cells or platelets) or growth‑factor medicines (such as G‑CSF, GM‑CSF, or erythropoietin) within 14 days before the first dose.
  • Has HIV infection and meets any of the following: detectable HIV‑1 RNA ≥ 50 copies/mL within the last 3 months; no recent CD4 count measurements; CD4 count ≤ 350 cells/mm³ in the past year; recent changes in antiretroviral therapy; history of HIV‑related lymphoma within 5 years; or received an HIV‑1 vaccine within 90 days. (Well‑controlled HIV without AIDS‑defining illness may be allowed.)
  • Has a liver enzyme (ALT) level more than 2.5 times the normal upper limit, or more than 5 times normal if liver metastases are present.
  • Has another cancer (other than the ovarian cancer being studied) that has gotten worse or needed treatment in the past 36 months, except for certain skin cancers or in‑situ cancers that have been completely removed.
  • Has a total bilirubin level more than 1.5 times the normal upper limit (except patients with Gilbert’s syndrome who meet specific bilirubin criteria).
  • Has cirrhosis or unstable liver or bile‑duct disease (such as fluid buildup in the abdomen, confusion, clotting problems, low blood protein, enlarged veins in the esophagus or stomach, or persistent yellowing of the skin). Stable, non‑cirrhotic liver disease may be allowed.
  • Has active hepatitis B surface antigen (HBsAg) or core antibody (HBcAb) at screening unless the person is on effective antiviral therapy for at least 14 days, has suppressed HBV DNA, and has been tested for hepatitis D virus.
  • Has a positive hepatitis C antibody test unless a follow‑up RNA test shows no active virus (indicating past, resolved infection).
  • Has a positive hepatitis C RNA test (indicating active infection).
  • Has a corrected QT interval (QTcF) longer than 470 milliseconds, which can increase the risk of abnormal heart rhythm.
  • Has a history within the past year of significant heart problems, such as uncontrolled cardiac disease, recent heart attack, severe heart failure (NYHA Class III or IV), or serious irregular heartbeat not controlled by medication.
  • For participants receiving pegylated liposomal doxorubicin (PLD) only: has a baseline left‑ventricular ejection fraction (LVEF) below 50% or below the normal range for the site.
  • Has any active kidney problem (infection, need for dialysis, or other serious kidney condition) that could affect safety. Managed kidney blockage may be allowed.
  • Has ever had an allogeneic or autologous bone‑marrow transplant or any solid‑organ transplant.
  • Is known to be allergic to any component of the study drug or its inactive ingredients, or has another allergy that the investigator believes makes participation unsafe.
  • Has untreated brain or central‑nervous‑system (CNS) metastases, or brain/CNS metastases that have grown or are causing new neurological symptoms. Previously treated and stable brain metastases may be allowed if steroids have been stopped for at least 14 days.
  • Has current interstitial lung disease (ILD) or pneumonitis, or a past history of these lung inflammatory conditions.
  • Has ongoing side effects from previous therapy that have not improved to mild (Grade 1) or baseline level, except for hair loss, hearing loss, skin color change, hormone replacement therapy, or mild nerve pain (Grade 2).
  • Has any serious or unstable medical condition (including infection), or serious or unstable psychiatric disorder, or any laboratory abnormality that could interfere with safety, consent, or ability to follow study procedures.
  • For participants planned to receive pembrolizumab as part of the physician’s choice regimen: has had a severe immune‑related adverse event (Grade 3 or higher), severe immune‑mediated neurological problems (such as myasthenia gravis, encephalitis, Guillain‑Barré syndrome, or transverse myelitis), severe skin reaction (such as Stevens‑Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome), or myocarditis (inflammation of the heart muscle).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name City Country Status
Medical University Of Vienna Vienna Austria
Medical University Of Graz Graz Austria
Medizinische Universitaet Innsbruck Innsbruck Austria
Technische Universitaet Dresden Dresden Germany
IRCCS Humanitas Research Hospital Rozzano Italy
Azienda Ospedaliero Universitaria Careggi Florence Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy
Oslo Universitetssykehus HF Oslo Norway
Comite Entreprise Paul Papin Angers France
Oncopole Claudius Regaud Toulouse France
Institut Curie – Site Paris Paris France

Other Sites

Site Name City Country Status
University Hospital Ostrava Ostrava Czechia
Turku University Hospital Turku Finland
Staedtisches Krankenhaus Kiel GmbH Kiel Germany
Studiengesellschaft Onkologie Bielefeld GbR Bielefeld Germany
Ospedale San Raffaele S.r.l. Milan Italy
Centro Di Riferimento Oncologico Di Aviano Aviano Italy
Istituto Europeo Di Oncologia S.r.l. Milan Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale Naples Italy
Centre Antoine Lacassagne Nice France
Knyrqwvn Llijo Gfkt Detmold Germany
Kzuurixk Glsvikzntz glowi Guetersloh Germany
Rfahhg Suvcfkoit Holbæk Denmark
Axciyaenpi Fdembqwxgbc Dfejqegw Knuyqhhy gkemv Frankfurt Germany
Hkqstu Hlobmhoa Herlev Denmark
Avabylgdn Hwbhtdgd Athens Greece
Cbghpip Uewcibtqhkrcrfoknali Bmofiu Khv Berlin Germany
Unwbvgxistkqlnkioumsb Dlaxwwutdqo Amj Duesseldorf Germany
Skkdtqvummup Hmesfhivo Geia Heilbronn Germany
Fodhmnrv Nyndfqsso Bcsx Brno Czechia
Htvtijsd Ukdtfaskld Ceozqjj Hrlyzxyu Helsinki Finland
Saiibgaxq Rzfibpv Umbmohpsga Meuttpc Csyoff Nijmegen The Netherlands
Ugsgkkztwqmyhpmifzqch Mvajqbvg Ali Munster Germany
Aoklhlg Ueprhhrhem Huyveflj Aalborg Denmark
Uuljobnuwbgdlnufrkcox Houneipvaq Aqs Heidelberg Germany
Mluanpo Cipgzg &khojtz Urfvgskefg Of Fhfukiyp Freiburg Im Breisgau Germany
Kzlmcsyp dks Uucvdndawyyo Mnqjcknr Avr Munich Germany
Vthtgknyk Fvtjoddh Njlgnbakd V Pshom Prague Czechia
Uyhekbudwapv Ltppfts Leipzig Germany
Ewbjmmwivm Cugmhs Aaxw Tobme Sdgg Athens Greece
Ubvjllkpkw Maswzma Cetzti Hlwuxvwidujgppqjv Hamburg Germany
Nqxgituyfhw Cgmzwd Iwyigbsej Amsterdam The Netherlands
Uyqbilpnkguxrjnuhwaax Eqmeg Aoa Essen Germany
Iaiadtme fqqs Khcmzbrfm Tzdpmekfstqtmkkjohv urp Iqgpdawqaoko Ujs gaiin Ulm Germany
Sdc Vemoertfxtdnukkudwi Gpvc Paderborn Germany
Seecjfuplufahd Oosmparxp Revowtqcse Grra Ravensburg Germany
Kkehzexy Efuiivneikiixigrmrjcdlig Hapttubgpjdmnzyba Essen Germany
Fhncbsstna Iwfdl Pvnhxkapxwc Sdm Mimxfb Pavia Italy
Abpkacb Oninzbrzher Pod Lmktrujesxsthhbnx Ctlnzuialr Catania Italy
Hntdd Bvjven Hg Bergen Norway
Jeelp Zxoibhahpo Hasselt Belgium
Cpsnvg hcofzajqkhb uufxrqnojgqde dg Lakks Liege Belgium
Utkyvwnjzowp Zgoafxhjgv Gxkr Gent Belgium
Uirssdztjg Dfsyo Sbzzk Dm Bjtpzwd Brescia Italy
Iznwvkbx Tuqgyh Bhcc Gjytrdsi Pgvih Ic Bari Italy
Apudrdu Uqead Lhrqyc Sejte Suqsddcch N 8 Bcftll Vicenza Italy
Aduducv Slmyx Squvguimv Tzerpoxicmyu Dvm Skbzl Lwdhs Varese Italy
Abjsqrp Otjwdhsfeex Uwusvpcgoqkkj Phomth Pisa Italy
Prkj Sswfj Lrkowvn Dv Vryfd Chambray Les Tours France
Cgeutd Ohgsl Lmulksz Lille France
Rsutfm Simka Scglee Uvstyixrhvdudaczqki Lund Sweden
Uztceco Uqqejpbfss Hqaypgzq Uppsala Sweden
Htijloi Pcjgf Drg Cpfjp Dgbimdvrxdzxk Plerin France
Crvfea Hukwheekkzf Lhvt Snr Pierre Benite France
Qzlmd Sxxaia Cgaugfrpi Hqcgxhex &gbrzxx Sthiykazdpl Uugctaryke Hfxkimbx &nyquhp Vflpnnl Ghnznojjuvycxqciph Gothenburg Sweden
Ibjbfoxdfht Dv Nxlfb Nancy France
Hdvzyqdi Uvyhxrbhyetzik Shzeyuhjuj &whbyij Hfmlvxf dy Hisljmgudcc STRASBOURG, Alsace France

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
Austria Austria
Not yet recruiting
14.09.2026
Belgium Belgium
Not yet recruiting
14.09.2026
Czechia Czechia
Not yet recruiting
14.09.2026
Denmark Denmark
Not yet recruiting
14.09.2026
Finland Finland
Not yet recruiting
14.09.2026
France France
Not yet recruiting
14.09.2026
Germany Germany
Not yet recruiting
14.09.2026
Greece Greece
Not yet recruiting
14.09.2026
Italy Italy
Not yet recruiting
14.09.2026
Norway Norway
Not yet recruiting
14.09.2026
Sweden Sweden
Not yet recruiting
14.09.2026
The Netherlands The Netherlands
Not yet recruiting
14.09.2026

Trial locations

Topotecan is a chemotherapy medicine that works by stopping cancer cells from copying their DNA, which prevents them from growing and dividing. In this trial it is given through an IV line directly into the bloodstream.

Paclitaxel is another chemotherapy drug that blocks the formation of structures needed for cancer cells to split. By keeping these structures from working, it stops the tumor cells from multiplying. It is also administered by IV infusion.

Pembrolizumab is an immunotherapy that helps the body’s own immune system see and attack cancer cells. It does this by blocking a protein that normally keeps the immune response in check. This medication is given by IV infusion.

Doxorubicin (pegylated liposomal) is a form of chemotherapy that is packaged in tiny fat‑like particles (liposomes) to reach the tumor while causing fewer side effects. It works by damaging the DNA inside cancer cells, stopping them from growing. It is delivered through an IV.

Gemcitabine is a chemotherapy drug that mimics building blocks of DNA, causing the cancer cells to stop making new DNA and die. It is given by IV infusion.

Bevacizumab is a targeted therapy that blocks a signal that tells tumors to grow new blood vessels. Without these vessels, the tumor gets less oxygen and nutrients, which can slow its growth. It is administered intravenously.

GSK5733584 is an experimental medicine being tested in this study. It is given by IV infusion and is being evaluated to see if it can improve outcomes for patients with platinum‑resistant ovarian cancer.

Investigated Diseases:

Ovarian neoplasm – A malignant growth that originates in the ovary, the organ that produces eggs and hormones. It can arise from the surface cells, germ cells, or supporting tissue of the ovary. The tumor often expands within the ovary and may spread to the surrounding pelvic structures. Cancer cells can travel through the abdominal cavity, leading to involvement of the peritoneum and other organs. Over time, the disease may recur after initial treatment.

Platinum‑resistant ovarian cancer – A form of ovarian cancer that no longer responds to platinum‑based chemotherapy after initial therapy. The cancer continues to grow or recur within six months of completing platinum treatment. It may spread within the pelvis and abdomen, affecting surrounding tissues. The disease can persist despite standard drug regimens, requiring alternative therapeutic approaches. It often presents with increasing tumor burden and symptoms related to abdominal involvement.

Trial ID:
2025-523361-25-00
Protocol code:
224031
NCT ID:
NCT07286266
Trial Phase:
Therapeutic confirmatory (Phase III)

Other Trials to Consider

  • Open‑Label Extension Study of Avutometinib Alone or with Defactinib in Patients with Recurrent Low‑Grade Serous Ovarian Cancer

    Recruiting

    2 1 1
    Investigated Diseases:
    Investigated Drugs:
    France
  • Phase 1/2 Study of CR-001 Safety and Dose Finding in Adults with Locally Advanced or Metastatic Solid Tumors

    Recruiting

    2 1 1
    France Ireland Italy Romania Spain