Daiichi Sankyo Company, Limited — Enhertu EMA EPAR variation assessment report (EMEA/H/C/005124, 2021)
Daiichi Sankyo Company, Limited · 2021 · EMA EPAR variation assessment report · company profile →
Report summary
This report details a Type II variation application for Enhertu (trastuzumab deruxtecan) to extend its indication to adult patients with unresectable or metastatic HER2-positive (IHC3+) solid tumors who have received prior treatment and lack satisfactory alternatives. The application is supported by pooled pop-PK analysis and interim results from the DESTINY-PanTumor02 (DP-02) study. The report outlines Enhertu's conditional EU authorization for various cancers, the DP-02 study design (a non-randomized, multi-cohort, single-arm trial), and extensive pharmacokinetic data. It highlights exposure-efficacy and exposure-safety modeling, noting a potential exposure-response relationship for overall survival and increased interstitial lung disease risk with higher exposure. Efficacy data from DP-02, DESTINY-LUNG01, and DESTINY-CRC02 trials are presented, including objective response rates, duration of response, progression-free survival, and overall survival across different tumor types and HER2 expression levels. Safety concerns, pharmacovigilance, and risk minimization measures for Enhertu are also discussed.
Key findings — cited to the page
| Overall rate of adjudicated all-cause grade ≥ 3 ILD/pneumonitis (IHC3+ supportive pool) | 2.9 % | · p.155 |
| Rate of ≥ grade 3 shift from baseline neutrophils decreased (bladder cancer patients in DP-02 study) | 34.2 % | DP-02 · p.155 |
| Grade ≥ 3 adverse events (DP-02 trial) | 63.3 % | DP-02 · p.155 |
| Overall rate of adjudicated all-cause grade ≥ 3 ILD/pneumonitis (DP-02 study) | 1.5 % | DP-02 · p.155 |
| Grade 3 LVEF decrease (IHC 3+ T-DXd Pool) | 0.3 % | · p.155 |
| Rate of ≥ grade 3 shift from baseline neutrophils decreased (DP-02 study) | 21.1 % | DP-02 · p.155 |
| incidence of ≥ Grade 3 ILD events | 2.5 % | · p.46 |
| incidence of ≥ Grade 3 ILD events | 10.0 % | DL01 study · p.46 |
| Grade ≥ 3 adverse events (IHC3+ subjects in DP-02) | 72.1 % | DP-02 · p.155 |
| Grade ≥ 3 adverse events (IHC 3+ supportive pool) | 55.1 % | · p.155 |
| Grade 2 LVEF decrease (IHC 3+ T-DXd Pool) | 15.6 % | · p.155 |
| Grade ≥ 3 AEs (DP-02 trial) | 63.3 % | DP-02 · p.156 |
Source: Daiichi Sankyo Company, Limited ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Oncology library →