NCT06899126

Study of Trastuzumab Deruxtecan, Pembrolizumab, and Platinum-based Chemotherapy in First-line HER2 Overexpressing Non-small Cell Lung Cancer

A Phase 3, Multicenter, Randomized, Open-label Trial of Trastuzumab Deruxtecan in Combination With Pembrolizumab Versus Platinum-based Chemotherapy in Combination With Pembrolizumab, as First-line Therapy in Participants With Locally Advanced Unresectable or Metastatic HER2 Overexpressing and PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer (DESTINY-Lung06)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 686 (estimated)
• Sponsor: Daiichi Sankyo · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This clinical trial is designed to assess the efficacy and safety of trastuzumab deruxtecan (T-DXd; Enhertu®) in combination with pembrolizumab versus platinum-based chemotherapy in combination with pembrolizumab in participants with no prior therapy for locally advanced unresectable or metastatic non-squamous NSCLC, whose tumors have HER2-overexpressing and PD-L1 TPS \<50% without known AGA that have locally available therapies targeting their AGAs in first-line advanced/metastatic setting.

Conditions

• Non-small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab Deruxtecan	T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)
DRUG	pembrolizumab	pembrolizumab will be administered at a dose of 200 mg IV Q3W
DRUG	Pemetrexed	Pemetrexed will be administered at a dose of 500 mg/m2 IV Q3W
DRUG	Chemotherapy	One of the following two will be administered in Arm B: Cisplatin at a dose of 75 mg/m2 IV or carboplatin AUC at a dose of 5 mg/mL/min IV

Timeline

• Start date: 2025-10-24
• Primary completion: 2030-03-05
• Completion: 2032-07-05
• First posted: 2025-03-27
• Last updated: 2026-01-08

Locations

100 sites across 12 countries: United States, Argentina, Belgium, Brazil, China, France, Japan, Malaysia, Portugal, South Korea, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study