GSK plc reported strong Phase I BEHOLD-1 results for mocertatug rezetecan, with response rates up to 67% in resistant gynecologic cancers, supporting advancement into five global Phase III trials.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
GSK plc reported encouraging early clinical activity for mocertatug rezetecan, a B7-H4–targeting antibody-drug conjugate, showing high confirmed response rates in heavily pretreated ovarian and endometrial cancers in the Phase I BEHOLD-1 trial. The findings position the investigational therapy for rapid transition into multiple Phase III studies across gynecologic malignancies.
At the highest evaluated doses, monotherapy achieved confirmed objective response rates of 62% in platinum-resistant ovarian cancer and 67% in recurrent or advanced endometrial cancer. Responses were observed across varying levels of B7-H4 expression, supporting the antigen as a broadly relevant target in gynecologic tumors. Median duration of response had not yet been reached at interim analysis.
Mechanism and Clinical Rationale
Mocertatug rezetecan is a B7-H4–directed antibody-drug conjugate composed of a fully human monoclonal antibody linked to a topoisomerase inhibitor payload with a drug-to-antibody ratio of six. B7-H4 is widely expressed in ovarian and endometrial cancers but limited in normal tissues, offering a precision-targeting opportunity in diseases where treatment options remain limited and response rates are typically modest.
Safety and Tolerability
Treatment discontinuations due to adverse events were uncommon at the highest doses, with no discontinuations reported in ovarian cancer and 4% in endometrial cancer. The most frequent treatment-related adverse event was nausea. Grade 3 or higher events occurred in 64% of ovarian cancer patients and 54% of endometrial cancer patients, mainly hematologic and consistent with ADC class effects. Interstitial lung disease or pneumonitis was reported in 3% of patients, and all cases were mild to moderate.
Dose interruptions and reductions were observed but remained manageable, supporting continued development. Based on these findings, 5.8 mg/kg has been selected as the recommended dose for upcoming pivotal trials.
Trial Design and Patient Population
BEHOLD-1 (NCT06431594) is a two-part, open-label Phase I study evaluating safety, tolerability, and efficacy. The trial enrolled 224 patients, including those with platinum-resistant ovarian cancer or advanced/recurrent endometrial cancer who had received one to three prior therapies. Patients received intravenous treatment every three weeks, with dose escalation followed by expansion cohorts.
Leadership Opinion
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK emphasized that gynecologic cancers remain difficult to treat and highlighted that the observed response rates support accelerating development into five global Phase III trials, including earlier treatment settings.
Ana Oaknin, Study Investigator for BEHOLD-1 trial also noted meaningful antitumor activity and a manageable safety profile, describing the results as encouraging for patients with limited therapeutic options.
Phase III Expansion Strategy
The BEHOLD clinical development program also includes the ongoing BEHOLD-2 combination study (NCT06796907). Mocertatug rezetecan is planned to advance into five pivotal global Phase III trials in 2026, beginning with platinum-resistant ovarian cancer in BEHOLD-Ovarian01 (NCT07286266) and second-line endometrial cancer in BEHOLD-Endometrial01 (NCT07286331). Additional Phase III studies will evaluate the therapy in platinum-sensitive ovarian cancer (BEHOLD-Ovarian02), as well as in first-line maintenance settings for ovarian cancer without homologous recombination deficiency (BEHOLD-Ovarian03) and mismatch-repair–proficient endometrial cancer (BEHOLD-Endometrial02).
Disease Burden
Endometrial cancer affects approximately 1.6 million people globally, while ovarian cancer affects about 843,000 individuals. Both diseases frequently present at advanced stages and have high recurrence rates, underscoring the need for more effective targeted therapies.
Reference
GSK presents positive data for B7-H4-targeted ADC in gynaecological cancers, 12 April 2026, GSK presents positive data for B7-H4-targeted ADC in gynaecological cancers | GSK
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 for Injection in Participants with Advanced Solid Tumors (BEHOLD-1), ClinicalTrials.gov ID NCT06431594, https://clinicaltrials.gov/study/NCT06431594
About the Writer
Nikita Jha BPharm is a pharmacy graduate with expertise in clinical research, pharmacovigilance, and medical writing. In her words, she is passionate about translating complex scientific data into clear, accurate healthcare communications that advance drug safety and patient care.