Summary
A phase 2 trial in resectable non-small cell lung cancer found a major pathological response in 70.1% of patients who underwent surgery after perioperative ivonescimab plus chemotherapy. The study was noncomparative, and median event-free survival was not mature at the analysis cutoff.
A phase 2 trial in China found a major pathological response in 47 of 67 patients with resectable non-small cell lung cancer (NSCLC) who underwent surgery after treatment with ivonescimab plus chemotherapy. The study also tested ivonescimab alone in a much smaller group. It was nonrandomized and noncomparative, so the results describe responses in the trial rather than a direct comparison between treatments.
Ivonescimab is a bispecific antibody that targets PD-1, an immune checkpoint, and VEGF, a protein involved in blood-vessel growth. The trial evaluated treatment before surgery, followed by surgery and adjuvant ivonescimab. It enrolled 90 adults with stage II to IIIB resectable NSCLC; patients with sensitising EGFR mutations or ALK translocations were excluded.
Pathological responses after treatment
The primary efficacy measure was major pathological response (MPR): no more than 10% of the resected primary tumour and lymph nodes could contain viable tumour cells. In the chemotherapy combination cohort, 47 of 67 operated patients achieved MPR, a rate of 70.1% (95% confidence interval: 57.7–80.7%). In the monotherapy cohort, 6 of 10 operated patients achieved MPR, or 60.0% (95% CI: 26.2–87.8%).
The trial met its prespecified MPR success criterion for the combination cohort: the lower bound of the two-sided 80% confidence interval exceeded a 41% historical control rate. That 41% was a historical benchmark, not a concurrent control group.
A pathological complete response (pCR), meaning no viable tumour cells in the resected primary tumour or lymph nodes, was reported in 34 of 67 operated patients in the combination cohort (50.7%) and 3 of 10 in the monotherapy cohort (30.0%). All patients who underwent surgery had an R0 resection, meaning the tumour was completely removed with clear margins. In total, 77 of the 90 enrolled patients underwent surgery.
These pathological measures show how much tumour remained at surgery. They are not the same as long-term survival outcomes. Median event-free survival was not mature at the data cutoff of 18 August 2025. The reported 12-month event-free survival rates were 83.3% in the combination cohort and 81.8% in the monotherapy cohort.
Safety and interpretation
Grade 3 or higher treatment-related adverse events were reported in 24 of 79 patients in the combination cohort (30.4%) and 4 of 11 in the monotherapy cohort (36.4%). No treatment-related deaths or grade 3 or higher haemorrhages were reported. One patient in the combination cohort had a treatment-related surgery delay; no treatment-related adverse event led to surgery being cancelled. Among patients who underwent surgery, ivonescimab-related surgery adverse events occurred in 7 of 67 in the combination cohort and 1 of 10 in the monotherapy cohort, with none graded 3 or higher.
The results make perioperative ivonescimab a candidate for further study, particularly in combination with chemotherapy. However, the monotherapy cohort included only 11 patients, and the noncomparative design cannot determine whether one regimen is more effective than another. The authors identify the small sample, study design and limited follow-up as limitations; a larger randomized phase 3 trial is needed to validate the findings and assess longer-term outcomes.