Trastuzumab deruxtecan (T-DXd) + bevacizumab (BEV) as first-line (1L) maintenance therapy in patients (pts) with human epidermal growth factor receptor 2 (HER2)–expressing ovarian cancer (OC): Results from the DESTINY-Ovarian01 (DO-01/ENGOT-ov89/GOG-3112/APGOT-OV13) safety run-in (SRI).

Abstract

5554 Background: HER2 immunohistochemistry (IHC) expression scores of 3+, 2+, or 1+ occur in up to ~6%, ~28%, and ~21% of OC cases, respectively. In DESTINY-PanTumor02, T-DXd, a HER2-directed antibody–drug conjugate, showed clinically meaningful antitumor activity in pts with heavily pretreated HER2-expressing OC, establishing HER2 as a targetable biomarker. BEV + chemotherapy, followed by maintenance BEV ± poly (ADP-ribose) polymerase inhibitors (PARPi), is a recommended 1L treatment; however, an unmet need remains for PARPi-ineligible pts with HER2-expressing OC. We report the SRI results from DO-01 (NCT06819007), a randomized, open-label, phase 3 trial evaluating T-DXd + BEV vs BEV alone as 1L maintenance therapy in pts with HER2-expressing OC. Methods: Pts with newly diagnosed, advanced, high-grade, locally or centrally determined HER2-expressing (IHC 3+/2+/1+) epithelial OC, with no disease progression after 1L chemotherapy + BEV, and ineligible for PARPi, were enrolled and received T-DXd 5.4 mg/kg + BEV 15 mg/kg intravenously every 3 weeks. Pts were treated for ≥2 cycles. Preliminary safety of T-DXd + BEV was assessed by dose-limiting toxicity (DLT; ~30% maximum acceptable rate) and the frequencies of treatment-emergent adverse events (TEAEs) and TEAEs of special interest. Results: At data cutoff (DCO; October 23, 2025), 21 pts received a median of 4 cycles (range, 2-8) of T-DXd + BEV; no pt withdrew before cycle 2. Median age was 57 years (range, 22-71) and 19 pts (90.5%) were Asian; 7 (33.3%) and 14 pts (66.7%) had FIGO stages III and IV at baseline, respectively. Median treatment duration was 3.0 mo (range, 1.4-5.5). At DCO, 20 pts (95.2%) completed DLT evaluation and remained on treatment; 1 withdrew after the DLT evaluation period. DLTs occurred in 2 pts (10.0%). TEAEs are shown in the Table. Grade ≥3 drug-related TEAEs occurred in 9 pts (42.9%). Drug-related TEAEs led to dose reduction in 5 pts (23.8%) and dose delay in 6 pts (28.6%). No drug-related TEAEs led to discontinuation or death. Most common drug-related TEAEs (>50%) were nausea (76.2%), leukopenia (52.4%), and neutropenia (52.4%). No cases of adjudicated drug-related interstitial lung disease or left ventricular dysfunction were reported. Conclusions: The preliminary safety profile of T-DXd + BEV was consistent with the known safety profiles of the individual agents, and no new safety signals were identified, supporting continued investigation of T-DXd + BEV in DO-01. Clinical trial information: NCT06819007 . Pts with events, n (%) T-DXd + BEVN = 21 Drug-related TEAEs 21 (100) Drug-related grade ≥3 TEAEs 9 (42.9) Drug-related TEAEs leading to discontinuation 0 Drug-related TEAEs leading to dose reduction 5 (23.8) Drug-related TEAEs leading to dose delay 6 (28.6) TEAEs with outcome of death 0