How has Akeso and Summit Therapeutics’ first in class PD 1/VEGF bispecific antibody ivonescimab performed versus pembrolizumab (Keytruda) in PD L1 positive locally advanced or metastatic non small cell lung cancer—including the Phase 3 China based HARMONi 2 trial’s overall surviv

Ivonescimab has produced the strongest head-to-head result yet reported against pembrolizumab in a China-only first-line PD-L1-positive NSCLC trial: a large PFS advantage and, now, a statistically significant interim OS benefit. That is compelling, but it is not yet sufficient to establish a Western first-line standard; global confirmatory evidence, fuller OS disclosure, and FDA decisions remain material uncertainties.

• HARMONi-2: directly versus Keytruda. In China-based Phase 3 HARMONi-2, ivonescimab monotherapy improved median PFS to 11.14 months from 5.82 months with pembrolizumab (HR 0.51; p<0.0001) in previously untreated PD-L1-positive locally advanced/metastatic NSCLC. 1

• Overall survival: In September 2026, Akeso reported that the pre-specified HARMONi-2 interim OS analysis met its key secondary endpoint, showing a statistically significant and clinically meaningful benefit over pembrolizumab as assessed by the independent monitoring committee. The companies have not yet publicly released the mature numerical OS results—median OS, HR, confidence interval, and subgroup results—so the magnitude and durability of that advantage still require conference presentation/publication. 2

• China regulatory validation—but not a Keytruda-comparator result. Ivonescimab already has Chinese approvals in NSCLC, including first-line use with platinum chemotherapy in PD-L1-positive non-squamous disease and, more recently, first-line treatment with chemotherapy in squamous NSCLC. 3 The squamous approval was supported by HARMONi-6, where ivonescimab plus chemotherapy beat tislelizumab plus chemotherapy on interim OS: median 27.9 versus 23.7 months, HR 0.66 (95% CI 0.50–0.87; p=0.0017). 4 That supports activity of the PD-1/VEGF mechanism, but it was against tislelizumab—not pembrolizumab—and in a Chinese population.

• A caution on HARMONi-6: Subsequent China-label information reportedly showed a less striking updated PFS estimate than the early disclosure, illustrating why mature datasets, full protocols, and independently reviewed publications matter more than initial top-line readouts. 5

What remains to be proved in the West

• Generalizability and regimen relevance: HARMONi-2 enrolled only Chinese patients and tested monotherapy against pembrolizumab monotherapy. In Western practice, many patients—particularly those with PD-L1 expression below 50%—receive chemo-immunotherapy rather than pembrolizumab alone. The key question is whether ivonescimab can reproduce a clinically meaningful survival benefit across non-Asian populations and against current relevant standards.

• HARMONi-3: The international first-line squamous-NSCLC study reportedly missed its first interim PFS statistical boundary. Updated subgroup OS signals may be encouraging, but subgroup, interim, and immature OS analyses cannot overturn a formally negative primary analysis. The planned later PFS/OS analyses are therefore important; publicly available evidence is insufficient to treat HARMONi-3 as confirmatory today. 5

• HARMONi-7 is the pivotal practical test for the Keytruda thesis. This ongoing global Phase 3 trial compares first-line ivonescimab monotherapy directly with pembrolizumab monotherapy in PD-L1–high advanced NSCLC. A positive, adequately powered global result—especially on OS and in Western participants—would address the central concern raised by the China-only HARMONi-2 data. Summit still lists HARMONi-7 among its multiregional Phase 3 program. 6

• Nearer-term FDA decision is in a different population. Summit submitted a BLA for ivonescimab plus platinum-doublet chemotherapy in previously treated EGFR-mutated, locally advanced/metastatic non-squamous NSCLC after a third-generation EGFR TKI. 7 The global HARMONi study met PFS, but the primary OS analysis was not statistically significant; that creates a real approval-risk and label-scope uncertainty even though later analyses showed an OS HR of 0.76 overall and in Western patients. 8

• Commercial stakes: Summit licensed rights outside Akeso’s retained territories in December 2022 for $500 million upfront plus up to $4.5 billion in regulatory and commercial milestones, with low-double-digit royalties. The arrangement covers major markets including the U.S., Canada, Europe, and Japan, making Western validation central to the deal’s value. 9

In short, HARMONi-2 has moved ivonescimab from a PFS story to a reported OS winner versus Keytruda in China. Its Western outlook now depends principally on disclosure of full HARMONi-2 OS data, the FDA’s view of PFS-positive/OS-not-significant EGFR-mutant data, and whether HARMONi-7 can reproduce a pembrolizumab advantage globally.