At the ESMO Congress 2026, Vanda Salutari (Rome, Italy) presented updated results from the phase I BEHOLD-1 trial (NCT06431594), evaluating mocertatug rezetecan (Mo-Rez), a B7-H4-targeted antibody–drug conjugate (ADC), in patients with platinum-resistant ovarian cancer.
The investigational therapy demonstrated promising antitumor activity, achieving a confirmed objective response rate (ORR) of 62% at the selected expansion dose of 5.8 mg/kg, with a median duration of response (DoR) of 12.2 months and median progression-free survival (PFS) of 11.1 months.
Methods
BEHOLD-1 is a two-part, open-label phase I study evaluating the safety and antitumor activity of mocertatug rezetecan, an ADC combining a humanized anti-B7-H4 monoclonal antibody with a topoisomerase I inhibitor payload.
B7-H4 is a transmembrane protein widely expressed in gynecologic tumors but with limited expression in normal tissues, making it a potential therapeutic target.
In the phase Ib dose-selection stage, 136 patients with platinum-resistant ovarian cancer were randomized to receive intravenous Mo-Rez at 2.8 mg/kg, 4.8 mg/kg, or 5.8 mg/kg every three weeks.
Patients had received a median of two prior lines of therapy. The primary endpoint was investigator-assessed confirmed ORR according to RECIST v1.1.
Key Takeaways
At the June 30, 2026, data cutoff, the median follow-up was 13.4 months.
- Confirmed objective response rate: 62% (28/45) at 5.8 mg/kg, compared with 57% (26/46) at 4.8 mg/kg and 36% (16/45) at 2.8 mg/kg.
- Median duration of response: 12.2 months at 5.8 mg/kg, compared with 6.9 months at 4.8 mg/kg and 7.8 months at 2.8 mg/kg.
- Median progression-free survival: 11.1 months at 5.8 mg/kg, compared with 8.3 months at 4.8 mg/kg and 5.6 months at 2.8 mg/kg.
- Safety: Grade ≥3 treatment-related adverse events occurred in 47% (64/135) of treated patients across all dose levels and 71% (32/45) at 5.8 mg/kg.
- Treatment discontinuation: Treatment-related adverse events led to discontinuation in 3% of patients overall and 2% at 5.8 mg/kg.
The 5.8 mg/kg dose demonstrated the longest median duration of response and progression-free survival among the evaluated dose levels.
Conclusion
The updated BEHOLD-1 findings demonstrated encouraging antitumor activity with mocertatug rezetecan in patients with platinum-resistant ovarian cancer.
The 62% confirmed response rate, 12.2-month median duration of response, and 11.1-month median PFS at 5.8 mg/kg support continued clinical development of this B7-H4-targeted ADC.
Although grade ≥3 treatment-related adverse events were relatively frequent at the selected dose, treatment discontinuation rates remained low. Further evaluation is needed to confirm the durability of clinical benefit and characterize long-term safety.
Enrollment in the 5.8 mg/kg expansion cohorts is ongoing, supporting further investigation of mocertatug rezetecan in platinum-resistant ovarian cancer.
Source: ESMO Congress 2026, Abstract LBA41; BEHOLD-1 (NCT06431594).
