Positive results from the TROPION-Breast01 phase 3 trial showed that a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC), datopotamab deruxtecan (Dato-DXd), demonstrated a statistically significant and clinically meaningful improvement in PFS compared to investigator’s choice of single-agent 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.
In the dual primary endpoint analysis, Dato-DXd reduced the risk of disease progression or death by 37 per cent compared to investigator’s choice of chemotherapy [HR=0.63; 95% CI: 0.52-0.76; p<0.0001] in patients with HR positive, HER2 low or negative metastatic breast cancer as assessed by blinded independent central review (BICR). Median PFS was 6.9 months in patients treated with Dato-DXd compared to 4.9 months in those treated with chemotherapy. A consistent benefit in PFS was observed across subgroups. Results also showed a confirmed objective response rate (ORR) of 36.4 per cent in patients treated with Dato-DXd compared to an ORR of 22.9 per cent in patients treated with chemotherapy. TROPION-Breast01 enrolled more than 700 patients at sites in Asia, Europe, North America, South America, and Africa.
Meanwhile, positive results from the pivotal TROPION-Lung01 phase 3 trial showed that Dato-DXd demonstrated a statistically significant improvement for the primary endpoint of PFS compared to docetaxel, the current standard of care, in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with at least one prior line of therapy.
Dato-DXd reduced the risk of disease progression or death by 25 per cent compared to docetaxel [HR=0.75; 95% CI: 0.62-0.91; p=0.004] as assessed by BICR. Median PFS was 4.4 months in patients treated with Dato-DXd compared to 3.7 months with docetaxel. Results also showed a confirmed ORR of 26.4 per cent in patients treated with Dato-DXd compared to an ORR of 12.8 per cent in patients treated with docetaxel. Median duration of response (DoR) was 7.1 months [95% CI: 5.6-10.9] in the Dato-DXd arm compared to 5.6 months [95% CI: 5.4-8.1] in the docetaxel arm.
These data were presented as two positive late-breaking presentations (LBA12) from the Dato-DXd clinical development programme, during the Presidential Symposium 3 at the ESMO 2023 Congress.