Daiichi Sankyo and AstraZeneca have begun dosing the first patient in two global, randomized Phase 3 trials of their collaborative treatment, datopotamab deruxtecan (Dato-DXd), in combination with durvalumab, an anti-PD-L1 therapy by AstraZeneca. These trials aim to evaluate the efficacy and safety of the combination in treating two types of breast cancer.
The trials, named TROPION-Breast04 and TROPION-Breast05, are part of an extensive clinical program to assess the TROP2 directed DXd antibody drug conjugate (ADC) datopotamab deruxtecan in different breast cancer settings. TROPION-Breast04 focuses on a neoadjuvant treatment with datopotamab deruxtecan plus durvalumab, followed by adjuvant durvalumab with or without chemotherapy, for patients with stage II-III triple-negative breast cancer (TNBC) or hormone receptor (HR) low, HER2 low, or negative breast cancer. TROPION-Breast05 investigates datopotamab deruxtecan alone and with durvalumab in patients with metastatic TNBC expressing PD-L1 (CPS ≥ 10).
Triple-negative breast cancer, which accounts for about 15% of all breast cancer diagnoses, is known for its aggressive nature and higher likelihood of recurrence and progression. Traditional treatments typically involve chemotherapy, sometimes in combination with immunotherapy. The trials also target patients with HR low, HER2 low, or negative breast cancer, a group often excluded from TNBC research but with poorer outcomes compared to those with hormone receptor-strongly positive tumors.
Mark Rutstein, MD, Global Head of Oncology Clinical Development at Daiichi Sankyo, pointed out the necessity for improved treatments for TNBC patients, despite recent advancements. These Phase 3 trials will determine if a combination of the TROP2 targeted ADC with durvalumab presents a more viable option for various breast cancer stages.
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer at AstraZeneca, shared that initial trials showed promising tumor responses with a manageable safety profile for the datopotamab deruxtecan and durvalumab combination. The initiation of these Phase 3 trials reflects a commitment to exploring the pairing’s potential across multiple TNBC settings and HR low disease.
Additionally, Daiichi Sankyo and AstraZeneca are conducting two more Phase 3 trials examining datopotamab deruxtecan in different TNBC contexts, expanding the research scope to potentially provide new treatment avenues for patients battling this aggressive cancer form.