EMA validates Enhertu® Type II variation application for lung cancer

The Type II variation application for Enhertu® for adults with advanced non-small cell lung cancer has been validated by the EMA.

EMA validates Enhertu® Type II variation application for lung cancer

The European Medicines Agency (EMA) has validated the Type II variation application for Enhertu® (trastuzumab deruxtecan) for adults with unresectable or metastatic non-small cell lung cancer (NSCLC).

Enhertu® is a HER2 directed antibody drug conjugate (ADC) developed and commercialised by Daiichi Sankyo and AstraZeneca. During two Phase II trials, Enhertu® demonstrated a clinically meaningful tumour response. Thus, the validation applies to adults whose tumours have activating HER2 (ERBB2) mutations and who have received a prior systemic therapy.

Commenting on the results of the Phase II trials, Dr Ken Takeshita, Global Head of R&D at Daiichi Sankyo shared: “Enhertu® is the first HER2 directed medicine shown to have a clinically meaningful tumour response in patients with previously treated HER2 mutant metastatic non-small cell lung cancer.”

The EMA’s validation means the application for Enhertu® in this indication is complete and will be subject to the scientific review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP).

This application is based on data from two Phase II trials:

  • DESTINY-Lung02 Phase II trial presented at the European Society for Medical Oncology (ESMO) 2022 Congress
  • DESTINY-Lung01 Phase II trial published in The New England Journal of Medicine with updated data also presented at ESMO 2022.


The Phase II trials behind the Type II variation application validation 

DESTINY-Lung02 trial

DESTINY-Lung02 (NCT04644237) is a global, randomised Phase II trial evaluating the safety and efficacy of Enhertu® in 152 patients with HER2 mutant metastatic NSCLC with disease recurrence or progression during or after at least one regimen of prior anticancer therapy that must have contained a platinum-based chemotherapy. Patients were randomised 2:1 to receive Enhertu® 5.4mg/kg (Cohort 1; n=102) or Enhertu® 6.4mg/kg (Cohort 2; n=50).

The primary endpoint of the trial is confirmed objective response rate (ORR). Secondary endpoints include confirmed disease control rate (DCR), duration of response (DoR) and progression free survival (PFS), overall survival (OS) and safety.

DESTINY-Lung01 trial

DESTINY-Lung01 (NCT03505710) is a global Phase II open-label, two-cohort trial evaluating the efficacy and safety of Enhertu® (5.4mg/kg or 6.4mg/kg) in 181 patients with HER2 mutant (cohort 2, n=91) or HER2 overexpressing (cohort 1 and 1a, n=90) (defined as immunohistochemistry (IHC) 3+ or IHC 2+) unresectable or metastatic non-squamous NSCLC relapsed from or refractory to standard treatment or for which no standard treatment is available.

The primary endpoint of the trial is confirmed ORR. Key secondary endpoints include DoR, DCR, PFS, OS and safety.

“As there are no approved therapies targeting HER2 mutant non-small cell lung cancer in Europe, we look forward to working closely with the European Medicines Agency to potentially bring a new treatment option to these patients,” concluded Dr Takeshita.