Mocertatug rezetecan (Mo-Rez) in patients with platinum-resistant ovarian cancer (PROC): Updated results with longer follow-up from the global BEHOLD-1 study

BEHOLD-1

Paziente / Popolazione Intervento / Esposizione Confronto Esito

In patients with platinum-resistant ovarian cancer, mocertatug rezetecan at the highest dose level achieved a confirmed objective response rate of 62% with a median progression-free survival of 11.1 months.

N

136pazienti

Disegno

Two-part, open-label, phase 1 study whose phase 1b dose-selection part randomised patients with platinum-resistant ovarian cancer to mocertatug rezetecan at 2.8, 4.8 or 5.8 mg/kg every three weeks (NCT06431594).

Esito

Confirmed objective response rate by investigator per RECIST 1.1.

RisultatoAt a median follow-up of 13.4 months, confirmed ORR was 62% (95% CI 46.5-76.2) at the highest dose level vs 57% (95% CI 41.1-71.1) at the intermediate and 36% (95% CI 21.9-51.2) at the lowest dose level. Median DoR was 12.2 months (95% CI 7.0-12.7) vs 6.9 and 7.8 months, and median PFS was 11.1 months (95% CI 8.3-13.9) vs 8.3 and 5.6 months. Grade ≥3 treatment-related adverse events occurred in 64 patients (47%) across all doses and in 32 patients (71%) at the highest dose. Discontinuation due to treatment-related adverse events was 3% overall and 2% at the highest dose.

Salutari V, Lheureux S, Lim MC, et al. Presented at ESMO Congress 2026, abstract LBA41, 24 October. Not yet published.

Discussione e critica

This randomised dose-selection cohort shows high response rates with mocertatug rezetecan in pretreated platinum-resistant ovarian cancer and supports the highest dose for expansion. It is an open-label phase 1 study with about 45 patients per arm, investigator-assessed response as a surrogate endpoint and no comparison with standard therapy, so it cannot show a benefit over existing treatment. The confidence intervals for response at the two higher doses overlap widely, overall survival is not reported and the efficacy results by B7-H4 expression are withheld. A Grade ≥3 treatment-related adverse event rate of 71% at the chosen dose deserves more scrutiny than the label 'acceptable safety profile' gives it, even with few discontinuations.