AstraZeneca, Daiichi Sankyo’s Dato-DXd improved PFS in breast cancer

Datopotamab deruxtecan demonstrated statistically significant and clinically meaningful progression-free survival benefit in patients with HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 Phase III trial.

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

AstraZeneca said in a press release Friday that positive high-level results from the TROPION-Breast01 Phase III trial showed datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant and clinically meaningful improvement for the primary endpoint of progression-free survival (PFS) compared to investigator’s choice of chemotherapy in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy.

A trend in improvement for the dual primary endpoint of overall survival (OS) was observed for datopotamab deruxtecan versus chemotherapy. Data for OS were not mature at this interim analysis and the trial will continue as planned to assess OS, AZ said.

According to the press release, the safety profile of datopotamab deruxtecan was consistent with previous clinical trials in breast cancer with no new safety signals identified. All grade interstitial lung disease rates were low.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said that today’s TROPION-Breast01 news is a significant development for patients with HR-positive, HER2-low or negative metastatic breast cancer whose tumours have become insensitive to endocrine therapy and who currently face poor outcomes.

Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo, said that the positive topline results from TROPION-Breast01 demonstrate the potential for datopotamab deruxtecan to become an important treatment option for patients with HR-positive, HER2-low or HER2-negative breast cancer in the second-line metastatic setting. Takeshita said: “We look forward to realising the full potential of this TROP2-directed antibody drug conjugate across breast cancer subtypes through our ongoing Phase III programme, including two trials in patients with triple-negative breast cancer.”

About brest bancer

More than two million people worldwide are diagnosed with breast cancer each year. HR-positive, HER2-low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases. Standard initial treatment for these patients is endocrine therapy but most patients with advanced disease will develop resistance, underscoring the need for additional options. TROP2 is a protein broadly expressed in HR-positive, HER2-low or negative breast cancer.

Additional Phase 3 trials

AstraZeneca and Daiichi Sankyo have two additional Phase III trials evaluating datopotamab deruxtecan in breast cancer. TROPION-Breast02 is comparing datopotamab deruxtecan to chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for anti-PDL1 therapy. TROPION-Breast03 is evaluating datopotamab deruxtecan with and without Imfinzi (durvalumab) versus investigator’s choice of therapy in patients with Stage I-III TNBC with residual disease after neoadjuvant therapy.