GSK’s Mo-Rez Shows Strong Phase I Results In Ovarian And Endometrial Cancer Trials

GSK plc has reported encouraging results from its global Phase I BEHOLD-1 trial evaluating mocertatug rezetecan (Mo-Rez), a novel antibody-drug conjugate (ADC) targeting the B7-H4 antigen. At the highest tested doses, the therapy demonstrated confirmed objective response rates (cORR) of 62% in platinum-resistant ovarian cancer (PROC) and 67% in recurrent or advanced endometrial cancer (EC), indicating strong early efficacy. These findings will be presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

Treatment options for patients with PROC and advanced EC remain limited, with generally modest response rates. The B7-H4 immune checkpoint, which is highly expressed in ovarian and endometrial tumors but minimally present in normal tissues, represents a promising target for precision therapies. The observed responses across varying levels of B7-H4 expression suggest that Mo-Rez could have broad applicability across gynecologic cancers.

Ana Oaknin, Study Investigator for BEHOLD-1, Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain said: “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. For patients with platinum-resistant ovarian cancer and recurrent endometrial cancer, these findings are particularly encouraging.”

From a safety perspective, the treatment showed a manageable profile. Very few patients discontinued therapy due to treatment-related adverse events, with none in the ovarian cancer group and only 4% in endometrial cancer. The most commonly reported side effect was nausea, while higher-grade adverse events were primarily hematologic, consistent with the ADC class. Rates of interstitial lung disease or pneumonitis were low and limited to mild or moderate cases.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “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.”

The interim analysis also showed that the median duration of response has not yet been reached, further supporting the durability of treatment benefit. Based on these results, a dose of 5.8 mg/kg has been selected for upcoming Phase III trials, BEHOLD-Ovarian01 and BEHOLD-Endometrial01, marking the next step in the clinical development of this promising therapy.