Mocertatug Rezetecan Shows Strong Responses in Ovarian and Endometrial Cancers

GSK has reported encouraging early clinical data from the global phase I BEHOLD-1 trial of mocertatug rezetecan, a B7-H4-targeted antibody-drug conjugate, in patients with platinum-resistant ovarian cancer and recurrent or advanced endometrial cancer, two settings in which treatment options remain limited and outcomes are often poor.

Response Rates in Difficult-to-Treat Disease

At the highest doses evaluated, mocertatug rezetecan monotherapy achieved a confirmed objective response rate of 62% in platinum-resistant ovarian cancer at 5.8 mg/kg, based on 21 responses among 34 patients. In recurrent or advanced endometrial cancer, the confirmed objective response rate reached 67% at 4.8 mg/kg, with 8 responses among 12 patients.

These results are notable in diseases where currently available therapies generally produce modest response rates. The interim analysis also showed that median duration of response had not yet been reached, suggesting that many responses were ongoing at the time of analysis.

Why B7-H4 Matters

B7-H4 is an immune checkpoint broadly expressed in ovarian and endometrial cancers, while showing low expression in normal tissues. That profile makes it an attractive therapeutic target, particularly for an ADC strategy designed to deliver cytotoxic treatment more selectively to tumour cells.

“In the early phase BEHOLD-1 study, we saw meaningful antitumour activity for this patient dataset, with response rates higher than typically seen in ADCs in development, and a manageable safety profile,” said Ana Oaknin, Study Investigator for BEHOLD-1, Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid. “For patients with platinum-resistant ovarian cancer and recurrent endometrial cancer, these findings are particularly encouraging.”

According to GSK, responses were seen across a range of B7-H4 expression levels, a finding that may support broader applicability in gynaecologic cancers.

Safety Profile Appears Manageable

At the highest doses studied, treatment discontinuation due to treatment-related adverse events was uncommon, reported in 0% of patients with platinum-resistant ovarian cancer and 4% of those with endometrial cancer.

The most common treatment-related adverse event was nausea, occurring in 82% of ovarian cancer patients and 75% of endometrial cancer patients. Grade 3 or higher treatment-related adverse events occurred in 64% and 54% of patients, respectively, and were mainly haematologic, consistent with expectations for this drug class. Interstitial lung disease or pneumonitis was reported in 3% of the overall safety population, affecting 5 of 178 patients, and all cases were grade 1 or 2.

“Treatment of gynaecological cancers remains a major challenge, with a pressing need for new therapies that offer improved response rates. With Mo-Rez, we now have compelling evidence of a promising clinical profile, with response rates that support accelerating development into five pivotal global phase III trials later this year across ovarian and endometrial cancers, including earlier line settings” said Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK.

Phase III Programme Moves Forward

Based on these data, GSK has selected 5.8 mg/kg as the recommended dose for the first phase III trials, BEHOLD-Ovarian01 and BEHOLD-Endometrial01. The company plans to launch five pivotal global phase III studies in 2026, spanning platinum-resistant and platinum-sensitive ovarian cancer, as well as maintenance settings in ovarian and endometrial cancer.

Results from the global phase I BEHOLD-1 trial, which remains ongoing in its dose-expansion phase, will be presented in a late-breaking oral session at the Society of Gynecologic Oncology Annual Meeting in San Juan, underscoring growing interest in mocertatug rezetecan as an investigational ADC in gynaecologic oncology.