TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer

• Published in: Future oncology (London, England) England), 2023-11, Vol.19 (35), p.2349-2359
• Main Authors: Dent, Rebecca A, Cescon, David W, Bachelot, Thomas, Jung, Kyung Hae, Shao, Zhi-Ming, Saji, Shigehira, Traina, Tiffany A, Vukovic, Petra, Mapiye, Darlington, Maxwell, Micah J, Schmid, Peter, Cortés, Javier
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal, Humanized - therapeutic use; antibody–drug conjugate (ADC); Antineoplastic Agents - therapeutic use; Breast Neoplasms - drug therapy; Cancer; datopotamab deruxtecan (Dato-DXd); Female; Humans; Immunoconjugates - therapeutic use; Life Sciences; PD-1/PD-L1; Prognosis; Receptor, ErbB-2; Triple Negative Breast Neoplasms; triple-negative breast cancer; Trophoblast cell surface antigen 2 (TROP2)
• ISSN: 1479-6694; 1744-8301
• DOI: 10.2217/fon-2023-0228

Despite recent treatment advances, the prognosis for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) remains poor. The antibody–drug conjugate datopotamab deruxtecan (Dato-DXd) is composed of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable, cleavable linker. The phase III TROPION-Breast02 trial in patients previously untreated for locally recurrent inoperable or metastatic TNBC, who are not candidates for PD-1/PD-L1 inhibitors is evaluating efficacy and safety of Dato-DXd versus investigator's choice of chemotherapy (ICC). Approximately 600 patients will be randomized 1:1 to Dato-DXd 6 mg/kg iv. every 3 weeks or ICC (paclitaxel, nab-paclitaxel, carboplatin, capecitabine or eribulin mesylate). Dual primary end points are progression-free survival by blinded independent central review and overall survival. Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is hard to treat. Tumors lack receptors for estrogen and progesterone, which means that standard endocrine therapy is ineffective, and it does not express HER2, so HER2 therapies are also not appropriate. However, the majority of TNBC tumors do possess a cell surface protein called TROP2 which provides a way of directing treatment inside tumor cells that is more selective than traditional chemotherapy. Datopotamab deruxtecan (Dato-DXd) is a drug that consists of two parts: datopotamab (an antibody) and DXd (the cancer-cell killing toxic component), which are joined via a stable linker. Datopotamab binds to the TROP2 protein found on TNBC tumors and is taken into the cell. The linker is then broken and releases DXd, which kills the tumor cell. By binding to cancer cells before releasing the payload, treatment is directed to the tumor, minimizing side effects in the rest of the body. The TROPION-Breast02 study aims to discover whether Dato-DXd is more effective than standard-of-care chemotherapy, allowing patients with TNBC to live longer without their breast cancer getting worse. This study is also looking at how Dato-DXd may affect patients' overall functioning and quality of life. TROPION-Breast02 will recruit approximately 600 patients who: Eligible patients will be randomly assigned to a treatment group in equal numbers to either Dato-DXd or an appropriate chemotherapy (one of five available options, chosen by the treating doctor). Each patient will generally continue to receive