A Study to Investigate Mocertatug Rezetecan Compared With Standard of Care in Participants With Platinum-resistant Ovarian Cancer (BEHOLD-Ovarian01)

A Randomized, Open-label, Multicenter, Phase 3 Study to Investigate Mocertatug Rezetecan Compared With Standard of Care in Participants With Platinum-resistant Ovarian Cancer

This study specifically aims to evaluate how well mocertatug rezetecan (Mo-Rez) works in treating ovarian cancer compared to standard treatments. The study also assesses whether Mo-Rez is safe and tolerated well by participants compared to standard treatments and aims to provide a better understanding of the main side effects of the drug.

Study Overview

• Status: Not yet recruiting
• Conditions: Ovarian Neoplasms
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Topotecan; Drug: Paclitaxel; Drug: Pegylated liposomal doxorubicin (PLD); Drug: Gemcitabine; Drug: Mocertatug rezetecan; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is at least 18 years of age and the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the Informed Consent Form (ICF).
• Has epithelial ovarian cancer, inclusive of primary peritoneal or fallopian-tube cancer with a histologically confirmed diagnosis of high grade serous, high grade endometrioid, or clear cell carcinoma, or carcinosarcoma that is resistant to platinum-based therapy.

Platinum-resistance is defined as follows:

• Participants who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum therapy, must have had a response (CR, PR, stable disease) and then progressed from >3 months to ≤6 months after the last dose of platinum therapy.

• Participants who have received >1 line of platinum therapy must have progressed on or ≤6 months after the date of the last dose of platinum therapy.

  • Has received at least 1 but no more than 4 prior lines of systemic anti-cancer therapy. Prior lines of therapy are defined as follows:

• Adjuvant ± neoadjuvant are considered one line of therapy.
• Maintenance therapy (e.g., bevacizumab, [poly adenosine diphosphate-ribosylation (ADP) ribose polymerase inhibitor (PARPi)] will be considered as part of the preceding line of therapy (i.e., not counted independently).
• Therapy changed to another agent in the same class due to toxicity in the absence of progression will be considered as part of the same line of therapy (i.e., not counted independently).
• Unplanned addition or switching to a new drug in a different class is considered a separate line of therapy.

• Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance.

  • Must have received prior treatment with the following therapies unless they have a contraindication per label or institutional guidelines as described below:

• Mirvetuximab soravtansine (MIRV),.
• The tumor demonstrates positive folate receptor alpha FRα expression (≥ 75% of viable tumor cells with moderate (2+) and/or strong (3+) membrane staining) per a test compliant to local regulation, AND
• Does not have a documented contraindication per label or local institutional guidelines, including but not limited to chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, monocular vision, peripheral neuropathy, interstitial lung disease, or hypersensitivity. AND
• It is available in the enrolment country. A regimen is considered available if it is approved and reimbursed (covered by national healthcare or private insurance) in the participating country.
• Bevacizumab, unless the participant has a documented contraindication per label or local institutional guidelines. Contraindications include but are not limited to vascular disorders (uncontrolled hypertension, arterial thromboembolic events), fistula, gastro-intestinal disorders (rectosigmoid involvement, bowel obstruction), delayed wound healing, bleeding diathesis (haemoptysis, epistaxis, pulmonary haemorrhage, acquired coagulopathy), nephrotic syndrome or significant proteinuria, or osteonecrosis of the jaw, or hypersensitivity

• PARPi, in participants with known or suspected deleterious germline or somatic BRCA mutations and who achieved a complete or partial response to platinum-based chemotherapy must have been treated with a poly ADP-ribose polymerase PARPi as maintenance treatment, if a PARPi is available in the enrolment country, unless the participants is not eligible for treatment with PARPi. A regimen is considered available if it is approved and reimbursed (covered by national healthcare or private insurance) in the participating country.

  • Has at least one Target lesion (TL) per RECIST 1.1, as determined by the investigator. Measurable lesions that have been previously irradiated and have been shown to be progressing following irradiation may be considered as TLs.
  • Has provided a Formalin fixed, paraffin embedded (FFPE) tumor tissue sample of sufficient quantity and quality for the central assessment of B7 homolog 4 protein (B7-H4) expression, with B7-H4 expression result available prior to date of randomization.

AND

• FR alpha expression
• In countries where mirvetuximab is available, an FR alpha expression result from a test compliant with local regulation or by central testing is required to determine eligibility.
• In countries where mirvetuximab is unavailable, an FFPE tumor tissue sample confirmed to be of sufficient quantity and quality must be provided. The FR alpha expression result is not required prior to randomisation or to determine eligibility.

AND

• PD-L1 expression, where a result from a local test is NOT available, an FFPE tumor tissue sample confirmed to be of sufficient quantity and quality must be provided. The PD-L1 expression result is not required prior to randomisation or to determine eligibility.

  • Is eligible to receive 1 of the standard of care interventions if randomized to physician's choice arm.
  • A female participant is eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies:
• Is a Participant of non-childbearing potential (PONCBP) OR

• Is a Participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, 30 days prior to Cycle 1 Day 1 (C1D1) and during the study intervention period and for at least 8 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.

  • A POCBP must have a negative, highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention

• If a urine test is positive or ambiguous and cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

  • Is capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the ICF and in the study protocol.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Has adequate organ function

Exclusion Criteria:

• Has primary platinum-refractory Ovarian Cancer (OC), defined as disease that did not respond to or has progressed within <3 months of the final dose of first line platinum containing chemotherapy.
• Has a malignancy (except disease under study) that has progressed or required active treatment within 36 months prior to date of randomization, except for basal cell or squamous cell carcinomas of the skin, in-situ carcinomas (e.g., breast, cervix, bladder) that have been resected with no evidence of metastatic disease, or that is otherwise considered cured by the investigator.
• 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 untreated brain or CNS metastases or brain/CNS metastases that have progressed (e.g., evidence of new or enlarging brain metastasis or new neurologic symptoms attributable to brain/CNS metastases). Participants with previously treated and clinically stable brain/CNS metastases and who have completed all corticosteroid therapy for ≥14 days prior to date of C1D1 are not excluded from participation.
• Has any evidence of current ILD or pneumonitis, or a prior history of ILD or non-infectious pneumonitis.
• Has ongoing adverse reaction(s) from prior therapy that has (have) not recovered to ≤Grade 1 or to the baseline status preceding prior therapy, excluding e.g., alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 neuropathy, or that the investigator, with the agreement of the sponsor, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study.
• Has any serious and/or unstable medical condition (including infection) or any serious and/or unstable 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, including requirements for the Follow-up Period of the study.
• For participants selected to receive the pembrolizumab-containing regimen as the intended physician's choice only: Has experienced any of the following with prior immunotherapy-any immune-mediated adverse event (imAE) ≥ Grade 3, immune-mediated severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson Syndrome [SJS], Toxic Epidermal Necrolysis [TEN], or drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome), or myocarditis of any grade
• For participants selected to receive bevacizumab as part of the pembrolizumab + paclitaxel ± bevacizumab intended physician's choice regimen only: Has a history of vascular disorders (uncontrolled hypertension, arterial thromboembolic events), fistula, gastro-intestinal disorders (rectosigmoid involvement, bowel obstruction), delayed wound healing, bleeding diathesis (hemoptysis, epistaxis, pulmonary hemorrhage, acquired coagulopathy), nephrotic syndrome or significant proteinuria, or osteonecrosis of the jaw, or hypersensitivity.
• Has had any major surgery within 28 days prior to date of C1D1 or received focal radiotherapy within 21 days prior to date of C1D1.
• Has received treatment with an investigational agent within 30 days prior to date of C1D1.
• Has received treatment with any cytotoxic chemotherapy drugs or other anti-tumor drugs (including endocrine therapy, molecular targeted therapy, immunotherapy, biotherapy, or investigational agent) within 30 days or 5 half-lives, whichever is shorter, prior to date of C1D1; or need to continue these drugs during study participation.
• Has ever received prior therapy with topoisomerase I inhibitors (e.g., topotecan) or ADC with a topo1i payload, or B7-H4 targeted therapy.
• Has received any live vaccine within 30 days prior to date of C1D1.
• Has received any transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including Granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 14 days prior to date of C1D1.
• For participants receiving PLD only: Has baseline Left ventricular ejection fraction (LVEF) <50% or lower than institutional lower limits of normal. Intolerance to PLD does not exclude a participant from the study if a different physician's choice option is chosen prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mocertatug rezetecan; Participants will receive Mocertatug rezetecan	Drug: Mocertatug rezetecan; Mocertatug rezetecan will be administered
Active Comparator: Standard of care; Participants will receive standard of care chemotherapy (Paclitaxel or Pembrolizumab + paclitaxel ± bevacizumab or PLD or Topotecan or Gemcitabine) as per investigator's choice	Drug: Pembrolizumab; Pembrolizumab will be administered; Drug: Topotecan; Topotecan will be administered; Drug: Paclitaxel; Paclitaxel will be administered; Drug: Pegylated liposomal doxorubicin (PLD); PLD will be administered; Drug: Gemcitabine; Gemcitabine will be administered; Drug: Bevacizumab; Bevacizumab will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by BICR	PFS is defined as the time from the date of randomization to the date of first documented Progressive Disease (PD) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) by Blinded independent central review (BICR) assessment or death from any cause, whichever occurs first.	Up to approximately 212 weeks
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause	Up to approximately 212 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS by investigator assessment	PFS is defined as the time from the date of randomization to the date of first documented PD per RECIST 1.1 by investigator assessment or death from any cause, whichever occurs first	Up to approximately 212 weeks
Objective response rate (ORR) by BICR	ORR is defined as the percentage of participants with best overall response of either complete response (CR) or partial response (PR) per RECIST 1.1 by BICR assessment	Up to approximately 212 weeks
Duration of Response (DOR) by BICR	DOR is defined as the time from the date of first documented objective response (CR or PR) per RECIST 1.1 by BICR assessment to the date of first documented Progressive Disease (PD) per RECIST 1.1 by BICR assessment or death due to any cause, whichever occurs first	Up to approximately 212 weeks
ORR by investigator assessment	ORR is defined as the percentage of participants with best overall response of either CR or PR per RECIST 1.1 by investigator assessment	Up to approximately 212 weeks
DOR by investigator assessment	DOR is defined as the time from the date of first documented objective response (CR or PR) per RECIST 1.1 by investigator assessment to the date of first documented PD per RECIST 1.1 by investigator assessment or death due to any cause, whichever occurs first	Up to approximately 212 weeks
PFS2	PFS2 is defined as the time from the date of randomization to the date of first documented investigator-assessed clinical or radiographical progression following the first subsequent anticancer therapy and after the progression event used for PFS, or death from any cause, whichever occurs first	Up to approximately 212 weeks
Number of participants with Treatment-emergent adverse event (TEAEs), Adverse event of special interest (AESIs) and Treatment-emergent serious adverse event (TESAEs)		Up to approximately 212 weeks
Number of participants with TEAEs/AESI/TESAEs leading to dose modifications or study intervention discontinuation		Up to approximately 212 weeks
Number of participants with changes in vital signs, laboratory tests (hematology and clinical chemistry), and Electrocardiogram (ECG)		Up to approximately 212 weeks
Serum concentration of Mo-Rez (conjugated antibody and free payload)		Up to approximately 212 weeks
Number of participants with Antidrug antibody (ADA) and Neutralizing Antibody (NAb) against Mo-Rez		Up to approximately 212 weeks
Titers of ADA against Mo-Rez		Up to approximately 212 weeks
Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score	The EORTC QLQ-C30 includes 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. The following domains will be measured: Global health status (GHS)/ Quality of Life (QoL), physical functioning, role functioning Participants responses on these items are . averaged and then transformed to scores . ranging from 0 to 100. Higher . score indicates better functioning or a better . overall state of health.	Up to approximately 212 weeks
Change from baseline in EORTC QLQ-Ovarian Cancer Module (OV28) score	The EORTC QLQ-OV28 includes a 28-item questionnaire for evaluating ovarian cancer-specific symptoms and concerns in participants of cancer clinical studies. These include items that assess symptoms in the abdominal/gastrointestinal domain. Scores are averaged and transformed to a 0 to 100 scale; higher scores indicate a greater symptom burden, while lower scores reflect fewer symptoms.	Up to approximately 212 weeks
Time to deterioration (TTD) of EORTC QLQ-OV28	TTD is defined as the time from the date of randomization to the first confirmed clinically meaningful deterioration on the abdominal/gastrointestinal symptom domain of the EORTC QLQ-OV28	Up to approximately 212 weeks
TTD of EORTC QLQ-C30	TTD is defined as the time from the date of randomization to the first confirmed clinically meaningful deterioration on any of the following EORTC QLQ-C30 domains: physical functioning, role functioning and Global Health Status (GHS)/ Quality of Life (QoL).	Up to approximately 212 weeks
Maximum Post-baseline Patient-reported outcome Common Terminology Criteria for Adverse Events (PRO-CTCAE) Score	The PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicities in participants in cancer clinical trials. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic toxicities drawn from the CTCAE. A subset of items selected from the PRO-CTCAE item library will be assessed. This measure captures maximum post-baseline PRO-CTCAE score for each frequency, severity and/or interference of symptomatic AEs	Up to approximately 212 weeks
CA-125 response rate as per Gynecologic Cancer InterGroup (GCIG) criteria.	Percentage of participants with a CA-125 response will be assessed	Up to approximately 212 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: GOG Foundation; European Network of Gynaecological Oncological Trial Groups (ENGOT); Asia-Pacific Gynecologic Oncology Trials Group

Study record dates

Study Major Dates

• Study Start (Estimated): June 24, 2026
• Primary Completion (Estimated): August 21, 2030
• Study Completion (Estimated): August 21, 2030

Study Registration Dates

• First Submitted: December 12, 2025
• First Submitted That Met QC Criteria: December 12, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Gemcitabine; Bevacizumab; Pembrolizumab; Topotecan; Paclitaxel; Antibody-drug conjugate; Platinum-resistant Ovarian Cancer; GSK5733584; Pegylated liposomal doxorubicin (PLD); BEHOLD-Ovarian01; Mo-Rez; Mocertatug rezetecan
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Ovarian Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Bevacizumab; Gemcitabine; Paclitaxel; Topotecan; pembrolizumab; liposomal doxorubicin
• Other Study ID Numbers: 224031; 2025-523361-25-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No