Development

Akeso's ivonescimab beats Keytruda on overall survival in advanced NSCLC

Edited by Robert McTiernan··2 min read
Akeso's ivonescimab beats Keytruda on overall survival in advanced NSCLC

Akeso's ivonescimab has now demonstrated a statistically significant overall survival benefit versus Merck's Keytruda (pembrolizumab) monotherapy in PD-L1-positive advanced non-small cell lung cancer (NSCLC), extending the drug's winning streak in head-to-head comparisons against the world's best-selling cancer drug. The result comes from a preplanned secondary endpoint analysis of the Phase III HARMONi-2 study, conducted by Akeso in China, and was announced by Miami-based Summit Therapeutics Inc. (Nasdaq: SMMT), which holds global rights to ivonescimab outside China.

The overall survival (OS) data add a second positive endpoint to a trial that already met its primary progression-free survival (PFS) endpoint. In the primary analysis, ivonescimab monotherapy reduced the risk of disease progression or death by 49% compared with pembrolizumab (HR 0.51; 95% CI: 0.38, 0.69; p<0.0001), with a median PFS of 11.14 months versus 5.82 months. The OS finding, declared statistically significant by an independent data monitoring committee, comes from a trial that enrolled 398 patients and is now scheduled for presentation at an upcoming medical conference; numerical OS data have not yet been disclosed.

Ivonescimab is a tetravalent bispecific antibody that simultaneously blocks PD-1 and VEGF in a single molecule, with the company asserting that cooperative binding concentrates activity preferentially in the tumor microenvironment where both targets are more highly expressed. The drug is approved in China for three NSCLC indications: post-EGFR-TKI non-squamous NSCLC (May 2024), first-line PD-L1-positive NSCLC (April 2025), and first-line squamous NSCLC in combination with chemotherapy (August 2026). It remains investigational in Summit's licensed territories, which include the US, Europe, and Japan.

The HARMONi-2 result adds to a growing Phase III dataset for ivonescimab. In HARMONi-6, ivonescimab plus chemotherapy reduced the risk of death by 34% compared with BeiGene's Tevimbra (tislelizumab) plus chemotherapy in first-line squamous NSCLC. Separate data from the HARMONi program in EGFR-mutated NSCLC have also shown an OS hazard ratio of 0.74 in the global population, although Summit has not reported formal statistical significance for that survival analysis

The AllSci BriefFree, systematic R&D and deal news. Daily.

For Summit, the result carries direct relevance to its own ongoing global trials. HARMONi-7, a Summit-sponsored Phase III study evaluating ivonescimab monotherapy versus pembrolizumab in patients with high PD-L1 expression, mirrors the HARMONi-2 design in a Western-eligible population. An OS benefit in the China-only HARMONi-2 study, particularly in the broader PD-L1-positive population, provides supportive evidence for the HARMONi-7 hypothesis. Summit also has a Biologics License Application under FDA review for ivonescimab plus chemotherapy in post-EGFR-TKI NSCLC, with a PDUFA date of November 14, 2026.

The immediate focus now shifts to the magnitude and consistency of the HARMONi-2 survival benefit. Until the full OS data are presented, the statistical win establishes that ivonescimab crossed an important threshold against pembrolizumab, but not yet how clinically consequential that advantage will prove to be.

Spot something wrong? Report an issue with this article