London, United Kingdom | April 13, 2026
GSK plc has announced positive clinical data from its Phase 1 BEHOLD-1 trial, demonstrating strong efficacy of its investigational B7-H4-targeted antibody-drug conjugate (ADC), mocertatug rezetecan (Mo-Rez), in patients with platinum-resistant ovarian cancer (PROC) and advanced endometrial cancer (EC). The study reported confirmed objective response rates (cORR) of 62% in ovarian cancer and 67% in endometrial cancer, highlighting the potential of this next-generation precision oncology therapy to address significant unmet medical needs. These results, presented at the Society of Gynecologic Oncology (SGO) Annual Meeting 2026, support the rapid advancement of Mo-Rez into five pivotal Phase 3 trials in 2026, marking a key milestone in GSK’s oncology pipeline.
Phase 1 Trial Demonstrates High Response Rates in Hard-to-Treat Cancers
The BEHOLD-1 clinical trial, an open-label Phase 1 study, evaluated the safety and efficacy of mocertatug rezetecan in patients with recurrent or advanced gynecologic cancers, including those with limited treatment options. At the highest dose levels, the therapy achieved remarkable tumor response rates, significantly exceeding typical outcomes seen in similar ADC therapies under development.
Notably, the study enrolled 224 patients across dose-escalation and expansion cohorts, providing robust early clinical evidence. The results are particularly impactful for platinum-resistant ovarian cancer, a disease setting where treatment options are scarce and survival outcomes remain poor. The ability of Mo-Rez to deliver consistent responses across varying levels of B7-H4 expression further reinforces its potential as a broadly applicable targeted therapy.
Innovative B7-H4 Targeting Enhances Precision Oncology
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Mocertatug rezetecan represents a novel class of B7-H4-targeted ADCs, designed to selectively bind to tumor cells expressing the B7-H4 immune checkpoint protein, which is highly prevalent in ovarian and endometrial cancers but minimally expressed in normal tissues. The ADC combines a fully human monoclonal antibody with a topoisomerase inhibitor payload, enabling precise delivery of cytotoxic agents directly to cancer cells.
This targeted mechanism enhances anti-tumor efficacy while reducing systemic toxicity, aligning with the broader shift toward precision medicine in oncology. The promising clinical activity observed in the trial validates B7-H4 as a critical therapeutic target, opening new avenues for the development of next-generation cancer treatments.
Favorable Safety Profile Supports Advancement to Phase 3 Trials
In addition to strong efficacy, the therapy demonstrated a manageable safety profile, with most treatment-related adverse events being consistent with the ADC class. Common side effects included nausea, hematologic toxicities, and fatigue, while serious adverse events such as interstitial lung disease were rare and predominantly mild. Importantly, treatment discontinuation rates were low, indicating good tolerability among patients.
These safety findings, combined with the observed clinical benefits, have supported GSK’s decision to initiate five global Phase 3 trials, including studies in both platinum-resistant and platinum-sensitive ovarian cancer, as well as endometrial cancer across different treatment settings. This comprehensive development strategy reflects strong confidence in the therapy’s potential to transform the standard of care in gynecologic oncology.
Expanding Opportunities in Gynecologic Oncology
Gynecologic cancers, including ovarian and endometrial cancers, represent a significant global health burden, with high recurrence rates and limited treatment options in advanced stages. The development of targeted therapies such as Mo-Rez is critical for improving patient outcomes and addressing unmet clinical needs. By advancing this ADC into late-stage clinical trials, GSK aims to expand therapeutic options and improve survival outcomes for patients with these challenging diseases. The integration of biomarker-driven approaches and targeted drug delivery systems is expected to play a pivotal role in shaping the future of oncology treatment paradigms.
The BEHOLD-1 trial results highlight a significant advancement in antibody-drug conjugate technology and precision oncology, demonstrating strong efficacy and a favorable safety profile in difficult-to-treat gynecologic cancers. With plans to advance into multiple Phase 3 trials, mocertatug rezetecan represents a promising new therapeutic option that could redefine treatment standards and improve patient outcomes. As GSK continues to expand its oncology pipeline, these findings underscore the growing importance of targeted therapies in addressing complex cancer challenges.
Source: GSK press release
