HARMONi-3 — Ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy in first-line metastatic NSCLC (HARMONi-3)

Phase 3 · Non-Small Cell Lung Cancer

Population

Untreated metastatic NSCLC (squamous and non-squamous) without actionable driver alterations.

Primary Endpoint

Progression-free survival and overall survival

Rationale

Chemo-immunotherapy with pembrolizumab is the broad first-line standard for driver-negative metastatic NSCLC. HARMONi-3 asks whether swapping pembrolizumab for the PD-1/VEGF bispecific ivonescimab, on the same chemotherapy backbone, improves outcomes across both squamous and non-squamous histologies.

What It Could Change

A positive result would challenge pembrolizumab-based chemo-immunotherapy as the default first-line regimen for driver-negative NSCLC.