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% (5.8 mg/kg n=21/34; 95% CI: 44, 78) in platinum-resistant ovarian cancer (PROC) and 67% (4.8 mg/kg n=8/12; 95% 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.
At the highest doses evaluated in BEHOLD-1, few patients needed to stop treatment because of a treatment-related adverse events (TRAE) (0% in PROC and 4% in EC). The most common TRAE was nausea (82% in PROC; 75% in EC). Grade ≥3 TRAEs occurred in 64% and 54% 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%; five 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.
About the BEHOLD clinical trial programme
The BEHOLD clinical programme is GSK’s global development plan that includes the BEHOLD-1 (NCT06431594) monotherapy study and the ongoing BEHOLD-2 (NCT06796907) combination study. Mo-Rez will advance to five pivotal global phase 3 trials in 2026, starting with PROC (BEHOLD-Ovarian01 / NCT07286266) and 2L EC (BEHOLD-Endometrial01 / NCT07286331).
Additional phase 3 studies will evaluate Mo‑Rez in platinum‑sensitive ovarian cancer (BEHOLD-Ovarian02) and in first‑line maintenance settings for ovarian cancer without homologous recombination deficiency (BEHOLD-Ovarian03) and mismatch‑repair–proficient endometrial cancer (BEHOLD-Endometrial02).
