Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC Following EGFR TKI and Platinum-Based Chemotherapy: HERTHENA-Lung01

Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC Following EGFR TKI and Platinum-Based Chemotherapy: HERTHENA-Lung01

Background

• EGFR-activating mutations occur in 14% to 38% of patients with NSCLC
• Salvage therapies after EGFR TKI therapy and platinum-based chemotherapy provide only limited and transient clinical benefit
• CNS metastases are common in this population, and therapies to ensure CNS control are needed
• A phase 1 study of HER3-DXd for advanced NSCLC demonstrated efficacy in patients with EGFR-activating mutations and diverse mechanisms of resistance to EGFR TKIs
• Promising data from the phase 1 trial led to initiation of the phase 2 HERTHENA-Lung01 trial of HER3-DXd in patients with EGFR-mutated NSCLC who were treated previously with EGFR TKI and platinum-based chemotherapy

Study Design

• Patient population had advanced EGFR-mutated NSCLC
  • Progression on most recent systemic therapy
  • Prior EGFR TKI and prior platinum-based chemotherapy
  • Inactive or previously treated asymptomatic brain metastases allowed
  • Pretreatment tumor tissue required
• R1:1 to fixed dose HER3-DXd IV Q3W or HER3-DXd uptitration
• Primary endpoint was cORR by BICR
• Key secondary endpoint was DOR by BICR

Results/Conclusions

• Clinically meaningful efficacy was observed in the overall population and across subgroups
• The safety profile of HER3-DXd was manageable and tolerable and consistent with previous reports
• HER3-DXd emerged as a promising therapy for patients with EGFR-mutated NSCLC after the failure of EGFR TKI and platinum-based chemotherapy, for whom available treatment options provide only limited efficacy