Daiichi Sankyo and AstraZeneca announced Initial results from the TROPION-PanTumor01 phase 1 trial of datopotamab deruxtecan (Dato-DXd) showed encouraging and durable efficacy in patients with heavily pretreated hormone receptor (HR) positive, HER2 low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridization [ISH]-) or HER2 negative (IHC 0) unresectable or metastatic breast cancer. Safety data were consistent with previous trials of datopotamab deruxtecan. Results were presented as a Spotlight Poster Discussion (Abstract #PD13-08) at the 2022 San Antonio Breast Cancer Symposium (#SABCS22).

Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca. Approximately 70% of breast cancer tumors are considered HR positive and HER2 low or negative. For patients with HR positive, HER2 low or negative metastatic breast cancer that progress on or are not suitable candidates for endocrine therapy, the current standard of care is single-agent chemotherapy.

In this cohort of TROPION-PanTumor01 (n=41) where patients previously received a median of five lines of treatment for metastatic disease, datopotamab deruxtecan demonstrated an objective response rate (ORR) of 27% as assessed by blinded independent central review (BICR). All responses were partial (n=11) and 56% of patients achieved stable disease (n=23). The disease control rate (DCR) was 85% and median progression-free survival (PFS) was 8.3 months (95% confidence interval [CI]: 5.5-11.1).

With median follow-up of 13.7 months (range, 9-16), the median duration of response (DoR; 95% CI: 4.4-NE) and the median overall survival (OS) had not been reached with 59% of patients alive for more than one year. The safety profile of datopotamab deruxtecan was consistent with previous data with no new safety signals identified. The most common grade 3 or higher treatment-emergent adverse events (TEAEs) were decreased lymphocyte count (15%), stomatitis (10%), anemia (7%), dyspnea (2%) and fatigue (2%).

Serious TEAEs were observed in six (15%) patients, including one death due to dyspnea that was not considered treatment-related. Treatment discontinuations due to an adverse event occurred in five (12%) patients. No cases of grade 3 or higher diarrhea or febrile neutropenia were observed.

One case of grade 3 interstitial lung disease was adjudicated as treatment-related. Patients in this cohort were heavily pretreated, receiving a median of five prior lines of treatment in the metastatic setting (range, 3-10). Prior treatments included CDK4/6 inhibitors (95%), capecitabine (83%), taxanes (59%), anthracyclines (54%), neoadjuvant chemotherapy (37%), mTOR inhibitors (29%) and PI3KCA inhibitors (20%).

As of data cut-off on July 22, 2022, five patients remained on study treatment.