Clinical Summary:

• Design/Population: The phase 1 BEHOLD-1 study evaluated the B7-H4–targeted antibody-drug conjugate mocertatug rezetecan in patients with platinum-resistant ovarian cancer  and advanced or recurrent endometrial cancer. 
• Key Outcomes: Mocertatug rezetecan demonstrated high response rates, low progression rates among responders, and manageable toxicity across both tumor types.
   Clinical Relevance: These findings support continued development and evaluation in ongoing phase 3 trials in ovarian and endometrial cancer.

Results from the phase 1 BEHOLD-1 trial demonstrated that mocertatug rezetecan, a B7-H4–targeted antibody-drug conjugate, showed encouraging antitumor activity among patients with platinum-resistant ovarian cancer and advanced or recurrent endometrial cancer.

These results were presented by Isabelle Ray-Coquard, MD, PhD, Université Claude Bernard, Lyon, France, at the European Society for Medical Oncology (ESMO) Gynecological Cancers Congress in Copenhagen, Denmark. 

In this open-label, dose-optimization and expansion study, 180 patients were randomized to receive mocertatug rezetecan once every 3 weeks at doses of 2.8 mg/kg, 4.8 mg/kg, or 5.8 mg/kg (ovarian cancer cohort; n = 131) or 2.8 mg/kg or 4.8 mg/kg (endometrial cancer cohort; n = 49). Primary end points included preliminary efficacy and safety.

At the highest dose levels, the confirmed objective response rate (ORR) was 62% in the ovarian cancer cohort and 67% in patients in the endometrial cancer cohort. Median time to response was 1.4 months and 1.5 months, respectively. At data cutoff, disease progression had occurred in 5% of responding patients in the ovarian cancer cohort and 12% of responding patients in the endometrial cancer cohort. Response was observed across B7-H4 expression levels. 

In the ovarian cancer cohort, confirmed ORR increased across dose levels, from 31% with 2.8 mg/kg to 53% with 4.8 mg/kg and 62% with 5.8 mg/kg. Among patients with prior poly (ADP-ribose) polymerase (PARP) inhibitor exposure, confirmed ORR was18%, 53%, and 65% across the 2.8-, 4.8-, and 5.8-mg/kg dose levels, respectively. Among patients previously treated with bevacizumab, confirmed ORR was 24%, 46%, and 59%, respectively. 

Grade ≥3 adverse events were reported in 53% of patients in the ovarian cancer cohort and 48% of patients in the endometrial cancer cohort. The most common grade ≥3 adverse events were neutropenia (27% and 23%) and anemia (8% and 19%). Treatment-related adverse events led to treatment discontinuation in 2% of patients in the ovarian cancer cohort and 4% of patients in the endometrial cancer cohort. No fatal treatment-related adverse events were reported.

“In BEHOLD-1, [mocertatug rezetecan] showed manageable safety and encouraging antitumor activity,” concluded Dr Ray-Coquard. “[Mocertatug rezetecan] 5.8 mg/kg [once every 3 weeks] will be evaluated in global phase 3 trials.” 

Source: 

Ray-Coquard IL, McKean WB, Dongen MV, et al. Mocertatug rezetecan (Mo-Rez), a B7-H4-targeted antibody–drug conjugate (ADC), in platinum-resistant ovarian cancer (PROC) and endometrial cancer (EC): Additional data from BEHOLD-1 study. Presented at ESMO Gynecological Cancers Congress. June 17-19, 2026. Copenhagen, Denmark. Abstract 110RO.