Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE:45680) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the TROPION-Breast01 phase 3 trial published in the Journal of Clinical Oncology. The recommendation will now be reviewed by the European Commission, which has the authority to grant marketing authorizations for medicines in the EU.

In TROPION-Breast01, datopotamab deruxtecan significantly reduced the risk of disease progression or death by 37% compared to investigator’s choice of chemotherapy (hazard ratio [HR]=0.63; 95% confidence interval [CI]: 0.52-0.76; p<0.0001) in patients with HR positive, HER2 negative metastatic breast cancer as assessed by blinded independent central review (BICR). Median progression-free survival (PFS) was 6.9 months in patients treated with datopotamab deruxtecan versus 4.9 months with chemotherapy. A confirmed objective response rate (ORR) of 36% was observed in the datopotamab deruxtecan arm compared to an ORR of 23% observed in the chemotherapy arm. Two (0.5%) complete responses (CR) and 131 (36%) partial responses (PR) were observed in the datopotamab deruxtecan arm compared to zero CR and 84 PR (23%) in the chemotherapy arm. The median duration of response (DoR) was 6.7 months (95% CI: 5.6-9.8) in the datopotamab deruxtecan arm compared to 5.7 (95% CI: 4.9-6.8) in the chemotherapy arm.

Datopotamab deruxtecan demonstrated a favorable safety profile over chemotherapy with no new safety concerns identified. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 21% and 45% of patients in the datopotamab deruxtecan and chemotherapy arms, respectively. The most common grade 3 or higher TRAEs were neutropenia (1% vs. 31%), stomatitis (6% vs. 3%), fatigue (2% vs. 2%) and anemia (1% vs. 2%). In the datopotamab deruxtecan arm, the all-grade interstitial lung disease (ILD) rate was low (3%) and the majority of events were low grade. There was one grade 5 ILD event adjudicated as drug related by an independent committee. The primary cause of death in this case was attributed to disease progression by the treating investigator.

“Disease progression after endocrine and initial chemotherapy is common in patients with metastatic HR positive, HER2 negative breast cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “This positive recommendation by the CHMP for datopotamab deruxtecan, which follows recent approvals in the U.S. and Japan, underscores the potential of this TROP2 directed antibody drug conjugate to offer a new treatment option to patients in the EU with this type of breast cancer.”

“Only one in three patients live more than five years after a metastatic HR positive, HER2 negative breast cancer diagnosis, underscoring the urgent need for additional effective therapies,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “Today’s recommendation for datopotamab deruxtecan brings us closer to offering these patients in the EU a new and needed alternative to conventional chemotherapy.”

Datopotamab deruxtecan is approved in Japan and the U.S. for the treatment of patients with unresectable or metastatic HR positive, HER2 negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. Additional regulatory submissions for datopotamab deruxtecan in breast cancer are under review in China and other regions.