GSK has announced positive findings from its global phase 1 BEHOLD-1 clinical trial for mocertatug rezetecan (or Mo-Rez for short), a novel Antibody-Drug Conjugate (ADC) targeting the B7-H4 antigen. At the highest doses evaluated, Mo-Rez monotherapy achieved confirmed Objective Response Rates (cORR) of 62 percent (5.8 mg/kg n=21/34; 95 percent CI: 44, 78) in Platinum-Resistant Ovarian Cancer (PROC) and 67 percent (4.8 mg/kg n=8/12; 95 percent CI: 35, 90) in recurrent or advanced Endometrial Cancer (EC). These data will be presented for the first time in a late-breaking oral session at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer in San Juan, Puerto Rico.

Currently, there are limited treatment options with modest response rates for patients with PROC and advanced EC. B7-H4 is an immune checkpoint that is widely expressed in ovarian and endometrial cancers and is low in normal tissues, providing potential for a differentiated precision-therapy. The response to Mo-Rez observed across a range of B7-H4 expression levels reinforces its broad potential in gynaecologic cancers and further validates the relevance of targeting B7-H4.

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 3 trials later this year across ovarian and endometrial cancers, including earlier line settings.”

At the highest doses evaluated in BEHOLD-1, few patients needed to stop treatment because of a Treatment-Related Adverse Event (TRAE) (0 percent in PROC and 4 percent in EC). The most common TRAE was nausea (82 percent in PROC; 75 percent in EC). Grade ≥3 TRAEs occurred in 64 percent and 54 percent patients in PROC and EC, respectively, and were predominantly haematologic, as expected for treatments in this class. Overall rates of interstitial lung disease or pneumonitis were low (3 percent; 5 out of 178 patients) and all cases were mild to moderate (grade 1-2). The interim analysis showed the median duration of response had not yet been reached. Based on the findings from this study, the recommended dose for the first of the phase 3 trials, BEHOLD-Ovarian01 and BEHOLD-Endometrial01, is 5.8 mg/kg.

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 antitumor 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.”