Rilvegostomig Plus Trastuzumab-Deruxtecan for Early-Stage Breast Cancer: The I-SPY2.2 Randomized Clinical Trial

Importance: The I-SPY2.2 trial tests personalized treatment strategies to improve outcomes while reducing exposure to standard chemotherapy in patients with high-risk early breast cancer (EBC).

Objective

To evaluate the efficacy and safety of trastuzumab-deruxtecan (T-DXd), an antibody drug conjugate targeting low ERBB2 (formerly HER2) expression, combined with rilvegostomig (R), a bispecific antibody targeting programmed cell death 1 protein and T-cell immunoglobulin and ITIM domain as initial therapy in I-SPY2.2 (RT-DXd). Design, setting, and participants: This phase 2, multicenter, adaptively randomized neoadjuvant trial enrolled patients with high-risk stage II/III ERBB2-negative EBC (including those with ERBB2 low/ultralow tumors), as stratified by hormone receptor (HR) status and response-predictive subtypes. It was conducted at 30 sites in the US; efficacy data were analyzed continuously during the trial to update probabilities and other analyses before publication.