GSK Reports Strong Results for B7-H4 ADC in Gynecological Cancers

An investigational antibody-drug conjugate (ADC) developed by GSK targeting B7-H4 is showing early signs of meaningful clinical activity in ovarian and endometrial cancers, two settings in which treatment options remain limited and outcomes are often poor.

GSK has reported positive findings from its Phase 1 BEHOLD-1 trial¹ evaluating mocertatug rezetecan (Mo-Rez), a next-generation ADC designed to target the B7-H4 immune checkpoint.

At the highest dose levels tested, Mo-Rez achieved confirmed objective response rates of 62% in platinum-resistant ovarian cancer (PROC) and 67% in recurrent or advanced endometrial cancer (EC). These results compare favorably with currently available therapies in these settings.

Both PROC and advanced EC are associated with limited treatment options and typically modest response rates, making these early efficacy signals particularly significant. The data were presented yesterday by Ana Oaknin, MD, PhD, head of the Gynecological Cancer Program at Hospital Universitario Puerta del Hierro, in a late-breaking session at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

Why Target B7-H4?

B7-H4 has emerged as a compelling therapeutic target in gynecologic cancers. The immune checkpoint protein is widely expressed in ovarian and endometrial tumors while remaining relatively low in normal tissues—an expression profile that makes it attractive for precision-targeted approaches.

Mo-Rez’s activity across a range of B7-H4 expression levels suggests the drug could have broad applicability, rather than being restricted to narrowly defined biomarker-positive populations. That flexibility could become a key differentiator as ADC development in solid tumors continues to accelerate.

Advancing Toward Phase III

Encouraged by the early data, GSK plans to advance Mo-Rez into five global Phase III trials beginning in 2026. These studies will evaluate the therapy across multiple disease settings, including:

• PROC
• Second-line EC
• Platinum-sensitive ovarian cancer
• First-line maintenance in ovarian cancer
• Maintenance treatment in EC

The first registrational studies, BEHOLD-Ovarian01 and BEHOLD-Endometrial01, will use a recommended dose of 5.8 mg/kg identified in the Phase I trial.

A Manageable Safety Profile with Expected Tradeoffs

Safety findings from BEHOLD-1 were broadly consistent with the ADC class. Few patients discontinued treatment due to adverse events (AEs), and the most common AE was nausea.

Higher-grade treatment-related AEs were observed in a substantial proportion of patients, particularly hematologic toxicities, which are typical for ADCs carrying cytotoxic payloads. Rates of interstitial lung disease and pneumonitis, however, were low and limited to mild-to-moderate cases.

While dose interruptions and reductions were relatively common, investigators described the overall safety profile as manageable, especially in the context of the observed efficacy.

Can Mo-Rez Shift the Treatment Landscape?

Gynecologic cancers—especially in recurrent or resistant settings—remain an area of significant unmet need. Recurrence rates are high, and survival outcomes tend to decline sharply once disease progresses after first-line therapy.

Mo-Rez enters a crowded but still evolving ADC landscape, with developers attempting to balance potency with tolerability while identifying the right targets. Its combination of high response rates, broad target expression, and a scalable development plan positions it as a potential contender in this space.

The key question now is whether these early signals will translate into durable benefit in larger, randomized trials. If confirmed, Mo-Rez could represent a meaningful advance for patients with few remaining options and further validate B7-H4 as a clinically relevant target in solid tumors.

References

1. Doherty, K. (2026, April 12). Mocertatug rezetecan displays early efficacy, tolerability in PROC and endometrial cancer. OncLive. https://www.onclive.com/view/mocertatug-rezetecan-displays-early-efficacy-tolerability-in-proc-and-endometrial-cancer