Ivonescimab outperforms pembrolizumab in lung cancer survival — but experts urge caution

Updated results from the HARMONi-2 trial show that ivonescimab — a bispecific antibody targeting both PD-1 and VEGF — significantly extended overall survival compared to pembrolizumab monotherapy in patients with PD-L1-positive advanced non-small cell lung cancer (NSCLC). The survival benefit held across both squamous and non-squamous histologies, and appeared strongest in patients with high PD-L1 expression (≥50%).

Despite the encouraging numbers, study discussant Dr. Mariana Brandão raised important caveats: the control arm used pembrolizumab alone, which doesn't reflect current global practice where chemo-immunotherapy combinations are standard. She also noted that the high-PD-L1 subgroup analysis was underpowered, and said she would not be changing her clinical practice based on these results alone.

By the Numbers

• Median OS: 30.8 vs. 22.6 months (ivonescimab vs. pembrolizumab); HR 0.73; P = .009
• 3-year OS rates: 45% vs. 33.1%
• PD-L1 ≥50% subgroup: median OS not reached vs. 23.2 months (HR 0.58)
• Grade ≥3 adverse events: 42% vs. 22% (ivonescimab vs. pembrolizumab)

Why it matters

Ivonescimab is already approved in China for this indication and is under FDA review for a separate NSCLC use. The global phase 3 HARMONi-7 trial — comparing ivonescimab to pembrolizumab specifically in PD-L1-high metastatic NSCLC — will be critical in determining whether these results can reshape first-line treatment standards worldwide.