415O First-line (1L) datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in patients (pts) with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: Patient-reported outcomes (PROs) from TROPION-Breast02

Background: Outcomes of antibody-drug conjugates (ADC) and HER2-targeted therapies after T-DXd in HER2+ metastatic breast cancer (MBC) remain unclear, with no prospective data available.SATEEN evaluated the activity and safety of SG, an anti-Trop2 ADC delivering a TOPO1 inhibitor, combined with trastuzumab for patients with HER2+ MBC previously treated with T-DXd.Methods: SATEEN was a single-arm phase II trial in patients with HER2+ MBC previously treated with taxane, trastuzumab, and T-DXd.Patients received SG (10 mg/kg IV, days 1 and 8, q21 days) plus trastuzumab (subcutaneous or IV) until progression or unacceptable toxicity.The primary endpoint was objective response rate (ORR).With a Simon's two-stage design (27 and 40 patients in stage 1 and 2, respectively), there was 90% power to distinguish a null ORR of 10% from an alternative ORR of 25%.Other endpoints included safety, clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and biomarker analyses.Results: A total of 27 patients were enrolled in stage 1 and started study therapy.Median age was 55 years, 59% had estrogen receptor-positive disease, 33% had brain metastases at enrollment (18% active, 15% stable), and patients had a median of 5 prior lines of HER2-directed therapy for MBC (range 1-17).One confirmed partial response was observed (ORR 3.7%, 95% CI 0.1%-19.0%);the trial did not meet its primary endpoint and was stopped after the 1 st stage.The 18-week CBR was 14.8% (95% CI 4.2%-33.7%).Median PFS was 2.3 months (95% CI, 2.0-3.5), and median OS was 9.2 months (95% CI, 7.6-NA).The most common grade 3 treatment-related adverse events (TRAEs) were neutropenia (59%), anemia (26%), and diarrhea (19%); there was one grade 5 TRAE (neutropenic sepsis with multi-organ failure) after which mandatory growth factor support was implemented in the study. Conclusions:In heavily pretreated HER2+ MBC after prior T-DXd, SG plus trastuzumab did not show clinically relevant activity.These prospective findings inform the activity of sequential TOPO1 inhibitor-based ADCs in HER2+ MBC and highlight the need for alternative strategies to optimize patients' outcomes.Clinical trial identification: NCT06100874.