A Study to Investigate Mocertatug Rezetecan With Bevacizumab Compared With Platinum Doublet With Bevacizumab in Participants With Platinum-sensitive Ovarian Cancer (BEHOLD-Ovarian02)

A Randomized, Open-Label, Multicenter, Phase 3 Study to Investigate Mocertatug Rezetecan With Bevacizumab Compared With Platinum Doublet With Bevacizumab in Participants With Platinum-Sensitive Ovarian Cancer

This study specifically aims to evaluate how well mocertatug rezetecan (Mo-Rez) in combination with bevacizumab works in treating platinum-sensitive ovarian cancer compared to standard treatments by checking whether it makes cancers smaller or disappear completely and if it helps participants live longer. The study also assesses whether Mo-Rez in combination with bevacizumab is safe and tolerated well by participants compared to standard treatments and aims to provide a better understanding of the main side effects of Mo-Rez.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 690
• 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, primary peritoneal, or fallopian-tube cancer with a histologically confirmed diagnosis of high grade serous, high grade endometrioid, clear cell carcinoma, or carcinosarcoma.

• Has recurrent or progressive disease after completion of at least 1 and a maximum of 2 previous lines of systemic anticancer therapy. Recurrent or progressive disease should be determined based on radiographic assessment according to RECIST 1.1 per investigator and/or clinical assessment of disease progression by investigator. Prior lines of therapy are defined as follows:

  • Adjuvant ± neoadjuvant is considered one line of therapy.
  • Maintenance therapy (e.g., bevacizumab, Poly 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 (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.
• Has platinum-sensitive disease and is suitable for platinum doublet chemotherapy with bevacizumab for the treatment of recurrent disease. Platinum sensitive disease is defined as recurrent or progressive disease >6 months after last dose of platinum-based chemotherapy.
• Has documented results of local testing (compliant to local regulations) for tumor and/or germline Breast Cancer Gene (BRCA1 and BRCA2) mutation. Participants with a known tumor or germline deleterious BRCA1 or BRCA2 mutation must have previously received PARPi maintenance therapy, alone or in combination with bevacizumab, if the participant was considered a candidate for this treatment and the treatment is locally available.
• Has provided a Formalin Fixed Paraffin Embedded (FFPE) tumor tissue sample sufficient for the central assessment of B7 homolog 4 protein (B7-H4) expression, with the result of B7-H4 expression testing available prior to the date of randomization.
• Is willing to use adequate contraception. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• A female participant is eligible to participate if they are not pregnant or breastfeeding, and 1 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), preferably 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.
• Is capable of giving signed informed consent including compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate organ function.

Exclusion Criteria:

• Plans to undergo interval secondary cytoreductive surgery for recurrent PSOC during induction therapy (platinum doublet and bevacizumab).
• Has a malignancy (except disease under study) that has progressed or required active treatment within the past 36 months prior to the date of randomization, except for basal cell or squamous cell carcinomas of the skin or 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 central nervous system (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 the date of C1D1 are not excluded from participation.
• Has any evidence of current Interstitial Lung Disease (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 alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, 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.
• Has clinically significant wound healing complications or incompletely healed wounds.
• Has a history or evidence of gastrointestinal perforation, tracheoesophageal fistula, or any Grade 4 fistula; has gastrointestinal fistula, visceral fistula, or abdominal abscess within 6 months prior to the date of C1D1; has osteonecrosis of the jaw.
• Has evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on computed tomography (CT) scan or clinical symptoms of bowel obstruction.
• Has clinically significant bleeding symptoms, significant bleeding tendency, or bleeding tumors within 30 days prior to the date of C1D1.
• Has congenital bleeding diathesis, acquired coagulopathy, recent pulmonary hemorrhage/hemoptysis (>2.5 mL of red blood or a half teaspoon) within 3 months prior to the date of C1D1.
• Has had any major surgery within 28 days prior to the date of C1D1 or history of focal radiotherapy within 21 days prior to the date of C1D1.
• Has received treatment with an investigational agent within 30 days prior to the date of C1D1.
• Has ever received prior therapy with topoisomerase 1 inhibitor [Topo1i] (e.g., topotecan) or antibody-Drug Conjugate (ADC) with a Topo1i warhead, or B7-H4 targeted therapy.
• Has received treatment with any cytotoxic chemotherapy drugs or other antitumor drugs (including endocrine therapy, molecular targeted therapy, immunotherapy or biotherapy) within 30 days or 5 half-lives, whichever is shorter, prior to the date of C1D1; or need to continue these drugs during study participation.
• Has received treatment with inhibitors of P-glycoprotein (P-gp), or Breast Cancer Resistant Protein (BCRP), or Organic Anion Transporting Polypeptides 1B1/1B3 (OATP1B1/1B3) within 7 days prior to the date of C1D1. Has received treatment with inducers of P-gp within 14 days prior to the date of C1D1.
• Has received any live vaccine within 30 days prior to the 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, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 14 days prior to date of C1D1.
• Has a history within 12 months prior to screening of clinically significant or uncontrolled cardiac disease, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure, or clinically significant arrhythmia not controlled by standard of care therapy.
• Has baseline Left Ventricular Ejection Fraction (LVEF) <50% or less than institutional lower limit of normal.
• Has clinically significant abnormal blood pressure according to investigator assessment, or inadequately treated and uncontrolled hypertension including history of hypertensive crisis; hypertensive encephalopathy; or adjustment of antihypertensive medications due to poor blood pressure control within 14 days prior to the date of C1D1.
• Has a history of nephrotic syndrome or Grade 3 proteinuria.
• Meets the following criteria for proteinuria during screening assessments: ≥2+ proteinuria on urine dipstick and 24-hour urine collection demonstrating ≥1 g of urine protein in 24 hours.

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 (Mo-Rez) + Bevacizumab; Participants will receive Mo-Rez + bevacizumab.	Drug: Bevacizumab; Bevacizumab will be administered; Drug: Mocertatug rezetecan (Mo-Rez); Mocertatug rezetecan will be administered
Active Comparator: Platinum doublet + Bevacizumab; Participants will receive platinum doublet chemotherapy (carboplatin with paclitaxel, gemcitabine, or pegylated liposomal doxorubicin [PLD]) and bevacizumab, followed by bevacizumab maintenance therapy.	Drug: Carboplatin; Carboplatin 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 disease progression (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 191 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 343 weeks
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 343 weeks
Time to Second Progression (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 the primary variable PFS, or death from any cause, whichever occurs first.	Up to approximately 343 weeks
Objective response rate (ORR) by investigator assessment	ORR is defined as the percentage of participants with a complete response (CR) or partial response (PR) per RECIST 1.1 by investigator assessment.	Up to approximately 343 weeks
Duration of Response (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 343 weeks
ORR by BICR	ORR is defined as the percentage of participants with a CR or PR per RECIST 1.1 by BICR.	Up to approximately 343 weeks
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 PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first.	Up to approximately 343 weeks
Time to first subsequent therapy (TFST)	TFST is defined as the time from the date of randomization to the date of initiation of subsequent therapy or death from any cause, whichever occurs first.	Up to approximately 343 weeks
Time to second subsequent therapy (TSST)	TSST is defined as the time from the date of randomization to the date of initiation of second subsequent therapy or death from any cause, whichever occurs first.	Up to approximately 343 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 343 weeks
Number of participants with TEAEs leading to dose modifications or study intervention discontinuation		Up to approximately 343 weeks
Number of participants with changes in vital signs, laboratory tests (hematology and clinical chemistry), and Electrocardiogram (ECG)		Up to approximately 343 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 343 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 343 weeks
Time to deterioration (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 343 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 343 weeks
Serum concentration of Mo-Rez		Up to approximately 343 weeks
Number of participants with Antidrug antibody (ADA) and Neutralizing Antibody (NAb) against Mo-Rez		Up to approximately 343 weeks
Titers of ADA against Mo-Rez		Up to approximately 343 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: GOG, ENGOT, APGOT

Study record dates

Study Major Dates

• Study Start (Estimated): September 22, 2026
• Primary Completion (Estimated): May 21, 2030
• Study Completion (Estimated): April 22, 2033

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Gemcitabine; Bevacizumab; Carboplatin; Antibody-Drug Conjugate; Paclitaxel; GSK5733584; Mocertatug Rezetecan; Mo-Rez; Platinum-Sensitive Ovarian Cancer (PSOC); Platinum Doublet; Pegylated Liposomal Doxorubicin (PLD); BEHOLD-Ovarian02
• 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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Bevacizumab; Gemcitabine; Carboplatin; Paclitaxel; liposomal doxorubicin
• Other Study ID Numbers: 224040; 2025-523366-24-00 (Ctis); GOG- 3136 (Other Identifier: Gynaecologic Oncology Group (GOG)); ENGOT-ov99 (Other Identifier: European Network of Gynaecological Oncological Trial Groups (ENGOT)); APGOT-OV19 (Other Identifier: Asia-Pacific Gynaecologic Oncology Trials Group (APGOT))

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