Trial Design

ENHERTU was evaluated in DESTINY-Lung02, a Phase 2, multicenter, multicohort, randomized, blinded, dose-optimization clinical trial1

DESTINY-Lung02 trial design1-3

ENHERTU was evaluated in DESTINY-Lung02, which was a Phase 2, multicenter, multicohort, randomized, blinded, dose-optimization clinical trial of adult patients with unresectable or metastatic non-squamous NSCLC who had activating HER2 mutations and disease progression after a prior systemic therapy. Patients were randomized 2:1 to receive ENHERTU at 5.4 mg/kg IV Q3W (n=101) or at 6.4 mg/kg IV Q3W (n=50) until disease progression or unacceptable toxicity. Only the results for the recommended dose of 5.4 mg/kg are described due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis. The major efficacy outcomes were confirmed ORR by BICR using RECIST v1.1 and DOR. The interim efficacy analysis included a prespecified cohort of 52 out of 101 patients. ENHERTU was evaluated in DESTINY-Lung02, which was a Phase 2, multicenter, multicohort, randomized, blinded, dose-optimization clinical trial of adult patients with unresectable or metastatic non-squamous NSCLC who had activating HER2 mutations and disease progression after a prior systemic therapy. Patients were randomized 2:1 to receive ENHERTU at 5.4 mg/kg IV Q3W (n=101) or at 6.4 mg/kg IV Q3W (n=50) until disease progression or unacceptable toxicity. Only the results for the recommended dose of 5.4 mg/kg are described due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis. The major efficacy outcomes were confirmed ORR by BICR using RECIST v1.1 and DOR. The interim efficacy analysis included a prespecified cohort of 52 out of 101 patients.
Major efficacy outcomes
  • Objective response rate by blinded independent central review based on RECIST v1.1
  • Duration of response
Select exclusion criteria1
  • History of steroid-dependent ILD/pneumonitis
  • Clinically significant cardiac disease
  • Clinically active brain metastasesc
  • ECOG performance status >1
Only the results for the recommended dose of 5.4 mg/kg are described due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis1

aPatients were prospectively selected for treatment with ENHERTU based on the presence of activating HER2 (ERBB2) mutations by local testing using tissue. Samples from another study were retrospectively tested using Oncomine™ Dx Target Test (Life Technologies Corporation, Tissue-test) and Guardant360® CDx test (Guardant Health Inc., Plasma test).1

bRadiographic tumor assessments were obtained every 6 weeks.1

cPatients with clinically inactive brain metastases were included in DESTINY-Lung02. Clinically active brain metastases were defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.2

Patient Characteristics

ENHERTU was studied in a range of patients with activating HER2-mutant 2L mNSCLC

Select patient demographics and clinical characteristics1

ECOG PS, Eastern Cooperative Oncology Group performance status; PD-1, programmed death 1; PD-L1, programmed death ligand 1.

HER2 mutations are more commonly found in patients with NSCLC who are younger,
female, and have never smoked4