Dr Tolaney on the Development of TROP2-Directed ADCs in Breast Cancer

Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, associate director, Susan F. Smith Center for Women’s Cancers; senior physician, Dana-Farber Cancer Institute, associate professor, medicine, Harvard Medical School, discusses the utility of TROP2-directed antibody-drug conjugates (ADCs) in the treatment of patients with breast cancer.

Currently, sacituzumab govitecan-hziy (Trodelvy) is the only FDA-approved TROP2-directed ADC for patients with breast cancer, but other promising TROP2-directed ADCs are in development, Tolaney begins. One such drug is datopotamab deruxtecan (Dato-DXd), which is being studied in patients with metastatic triple-negative breast cancer (TNBC), specifically in the first-line setting, she explains. The ongoing phase 3 TROPION-Breast02 trial (NCT05374512) is comparing Dato-DXd with standard chemotherapy, and the phase 3 TROPION-Breast05 trial (NCT06103864) is evaluating the combination of Dato-DXd with or without durvalumab (Imfinzi) vs chemotherapy plus pembrolizumab (Keytruda) in the PD-L1–positive first-line setting, Tolaney reports. The results of these trials will help determine the role of Dato-DXd in treating patients with TNBC, according to Tolaney.

Another TROP2-directed ADC under investigation in patients with TNBC is sacituzumab tirumotecan (MK-2870/SKB264), which targets TROP2 and includes a belotecan-derivative topoisomerase I inhibitor payload, similar to sacituzumab govitecan, she continues. Data presented at the 2024 ASCO Annual Meeting fromthe phase 3 OptiTROP-Breast01 trial (NCT05347134), based in China, showed that the agent improved both progression-free survival and overall survival when compared head to head with chemotherapy in a pretreated population of patients with locally recurrent or metastatic TNBC. This trial’s design closely mirrors that of the phase 3 ASCENT trial (NCT02574455), which evaluated sacituzumab govitecan in relapsed/refractory metastatic TNBC, Tolaney says.

Given these findings, there is considerable interest in exploring sacituzumab tirumotecan’s efficacy in less heavily pretreated populations within the metastatic setting, she continues. As these new TROP2-directed ADCs are studied further, more data will emerge, potentially expanding treatment options for patients with TNBC, Tolaney explains. The ongoing research with these agents may create a future where multiple TROP2-directed therapies are available for patients with TNBC, Tolaney concludes.