Ivonescimab before and after surgery met its goal in resectable lung cancer

When lung cancer is caught early enough to operate on, surgery alone often is not the end of it: a substantial share of tumours come back. That is why treatment given around the operation — before it to shrink the tumour, after it to clear what is left — has become a major front in lung-cancer research. A phase 2 trial published in Nature Medicine on 4 November tested a new drug in that window [s1].

What the drug is

Ivonescimab is a bispecific antibody: a single molecule engineered to bind two targets at once [s1]. One is PD-1, the checkpoint that tumours use to switch off an immune attack — the same target as established immunotherapy drugs. The other is VEGF, a signal tumours use to build the blood supply they need to grow. The idea is that blocking both together does more than blocking either alone.

The trial, registered as NCT05247684, asked whether giving ivonescimab around surgery could produce the kind of deep tumour response that tends to track with better long-term outcomes in this setting [s1][s2].

How the trial was built

This was a nonrandomised, noncomparative phase 2 trial [s1]. That design matters for reading the result, so it is worth stating plainly: everyone enrolled received ivonescimab, and there was no parallel group given a different treatment to compare against directly.

Participants were split into two cohorts by what they received before surgery. Cohort 1 had ivonescimab on its own as neoadjuvant — pre-surgical — treatment. Cohort 2 had ivonescimab combined with chemotherapy. Both cohorts then went to surgery and afterwards received ivonescimab as adjuvant treatment [s1].

The main yardstick was the major pathological response rate: the proportion of patients whose removed tumour, examined under a microscope after surgery, showed only a small amount of surviving cancer. A major pathological response means 10% or less of the tumour remained viable, and it is used as an early readout because it has been linked to better survival, though it is not the same thing as living longer.

What it found

In cohort 2 — ivonescimab plus chemotherapy — the major pathological response rate was 70.1% (47 of 67 patients; 95% confidence interval 57.7–80.7) [s1]. The trial was designed to beat a historical control rate of 41%, and the lower bound of the response's confidence interval sat above that mark, so the primary endpoint was met [s1].

In cohort 1 — ivonescimab alone — the rate was 60.0% (6 of 10 patients; 95% CI 26.2–87.8) [s1]. That cohort was small, and the wide confidence interval reflects it. Among the patients who did reach a major pathological response, the response tended to be deep: 83.3% (5 of 6) in cohort 1 and 97.9% (46 of 47) in cohort 2 had 5% or less viable tumour remaining [s1].

On safety, grade 3 or worse treatment-related adverse events occurred in 36.4% (4 of 11) of patients in cohort 1 and 30.4% (24 of 79) in cohort 2 [s1]. There was no grade 3 or worse bleeding and no treatment-related death [s1]. A treatment-related delay to surgery occurred in one patient (1.3%), and surgery-related adverse events attributed to ivonescimab occurred in 10.0% (1 of 10) and 10.4% (7 of 67) of the two cohorts, with none grade 3 or worse [s1]. Bleeding is a specific concern for drugs that block VEGF around an operation, so the absence of severe haemorrhage is a point the authors note [s1].

What is, and is not, established

What this trial supports is narrow but real: in operable non-small-cell lung cancer, perioperative ivonescimab with chemotherapy produced a major pathological response in about 70% of patients and cleared its prespecified bar [s1]. The authors frame the combination as a promising strategy worth testing further [s1].

The limits are as important as the result. There was no randomised comparison group, so the trial cannot say how ivonescimab stacks up against the chemotherapy-plus-immunotherapy regimens already used before lung surgery — the 41% figure is a historical benchmark, not a head-to-head arm [s1]. The monotherapy cohort had just ten patients [s1]. Major pathological response is a surrogate; whether these patients actually live longer or stay cancer-free is not answered here and needs longer follow-up [s1]. And ivonescimab in this setting is investigational — this describes a trial, not an approved use.

Anyone being treated around lung surgery who develops unusual bleeding or bruising, breathlessness, or a new cough should contact their team. This article describes research and is not medical advice.