HARMONi-2 — Ivonescimab versus pembrolizumab as first-line therapy for PD-L1-positive advanced NSCLC (HARMONi-2)

Phase 3 · Non-Small Cell Lung Cancer

Population

Untreated locally advanced or metastatic NSCLC with PD-L1 TPS ≥1% and no EGFR/ALK alterations.

Primary Endpoint

Progression-free survival

Rationale

Single-agent pembrolizumab is a standard first-line option for PD-L1-positive NSCLC, but responses are often short-lived. HARMONi-2 tests whether ivonescimab — a PD-1/VEGF bispecific antibody that blocks two pathways at once — can outperform pembrolizumab head-to-head, the first such comparison for any agent in this setting.

What It Could Change

A win would be the first time a single agent beats pembrolizumab in first-line PD-L1-positive NSCLC, potentially displacing it as the monotherapy backbone.