ENGOT-ov77/GINECO/REJOICE study

Raludotatug deruxtecan (R-DXd), a novel antibody–drug conjugate targeting CDH6, was evaluated in the phase 2 ENGOT-ov77/GINECO/REJOICE study in patients with platinum-resistant ovarian cancer. Eligible participants had received one to three prior lines of systemic therapy, including bevacizumab and PARP inhibitors in the majority of cases. Patients were randomised to receive different doses of R-DXd to determine the optimal balance between efficacy and safety.

Across all dose cohorts, R-DXd demonstrated substantial antitumour activity, with confirmed objective response rates exceeding 50% and disease control rates above 77%. The median time to response was approximately seven weeks, and most patients exhibited measurable tumour shrinkage. These findings suggest rapid and clinically meaningful activity of R-DXd even in heavily pretreated, platinum-resistant populations.

Regarding safety, treatment-related grade ≥3 adverse events were consistent with expectations for this class of agents. The rate of treatment discontinuation due to toxicity was low (approximately 5%). Dose reductions and delays occurred more frequently in the 6.4 mg/kg cohort. The most common adverse events included nausea, anaemia, asthenia, and neutropenia. Interstitial lung disease was observed in about 3% of patients, predominantly grade 1–2, with a single grade 3 event. The overall safety profile of the 5.6 mg/kg cohort was comparable to that of the 4.8 mg/kg group, while the 6.4 mg/kg dose was associated with a higher incidence of adverse events.

Importantly, R-DXd exhibited clinical activity across a broad range of CDH6 expression levels, indicating that therapeutic efficacy is not restricted to high-expression tumours. Based on the observed efficacy and tolerability, 5.6 mg/kg was identified as the optimal dose for further evaluation. The phase 3 REJOICE-OV1 trial will further assess R-DXd at the 5.6 mg/kg dose compared with physician’s choice of chemotherapy.