Key Clinical Summary: 

• Design/Population: The phase 1 BEHOLD-1 study evaluated mocertatug rezetecan in patients with advanced solid tumors, including platinum-resistant ovarian cancer and recurrent endometrial cancer. 
• Key Outcomes: High response rates were observed, with objective response exceeding 60% in both tumor types at higher dose levels. Adverse events were primarily hematologic and dose-dependent but manageable, with low discontinuation rates.
• Clinical Relevance: B7-H4–targeted therapy represents a promising approach in gynecologic cancers. These findings support ongoing phase 3 trials to confirm efficacy and define its role in clinical practice.

Results from the phase 1 BEHOLD-1 study demonstrate that mocertatug rezetecan, a novel B7-H4–targeted antibody-drug conjugate, shows strong clinical efficacy and safety among patients with platinum-resistant ovarian cancer and recurrent endometrial cancer. 

These findings were presented by Ana Oaknin, MD, PhD, Vall d´Hebron University Hospital, Barcelona, Spain, at the 2026 Society of Gynecologic Oncology (SGO) Annual Meeting in San Juan, Puerto Rico.

In this open-label study, 44 patients with advanced solid tumors were enrolled in the phase 1a dose-escalation cohort to receive intravenous mocertatug rezetecan across 4 dose levels until disease progression or unacceptable toxicity. In the phase 1b dose-expansion cohort, 178 patients with either platinum-resistant ovarian cancer (n = 130) or endometrial cancer (n = 48) who had received 1 to 3 prior lines of therapy were randomized to receive mocertatug rezetecan at 2 or 3 dose levels. Primary end points included maximum tolerated dose, objective response rate (ORR), and safety.

At phase 1a analysis, the maximum tolerated dose was not reached, and 5.8 mg/kg administered once every 3 weeks was identified as the maximum applicable dose. Two dose-limiting toxicities were reported in 1 patient (febrile neutropenia and thrombocytopenia). 

At phase 1b analysis, the highest dose level was 5.8 mg/kg for patients with ovarian cancer and 4.8 mg/kg for patients with endometrial cancer. Confirmed ORR was 62% and 67%, respectively. Median duration of response not reached. The most reported any-grade treatment-related adverse event was nausea, occurring in 68% of patients with ovarian cancer and 67% of patients with endometrial cancer. Grade ≥ 3 treatment-related adverse events occurred in 42% and 35% of patients, respectively, and most frequently included neutrophil count decrease, neutropenia, and anemia. The incidence of high-grade events, as well as dose delays and reductions, was dose-dependent. Treatment discontinuation due to adverse events occurred in 2% and 4% of patients, respectively.

“[Mocertatug rezetecan] showed encouraging antitumour activity in [patients] with [platinum-resistant ovarian cancer] and [endometrial cancer] and had a manageable safety profile,” concluded Dr Oaknin. “[Mocertatug rezetecan] is being evaluated in global Phase 3 trials in [platinum-resistant ovarian cancer].” 

Source: 

Oaknin A, McKean W, van Dongen M, et al. Mocertatug rezetecan (GSK5733584), a B7-H4-targeted antibody-drug conjugate (ADC), in platinum-resistant ovarian cancer (PROC) and endometrial cancer (EC): First results from the global BEHOLD-1 study. Presented at SGO Annual Meeting on Women’s Cancer. April 10 - 13, 2026; San Juan, Puerto Rico. LBA6.