Phase 2 Trial Reports Pathological Responses With Perioperative Ivonescimab in Resectable NSCLC

This multicenter, nonrandomized, noncomparative phase 2 trial evaluated perioperative ivonescimab, a bispecific antibody targeting PD-1 and VEGF, in patients with resectable stage II–IIIB non-small cell lung cancer (NSCLC) without sensitizing EGFR mutations or ALK translocations. Patients received neoadjuvant ivonescimab alone or with platinum-paclitaxel chemotherapy, followed by surgery and adjuvant ivonescimab. The primary endpoints were major pathological response (MPR) and safety. The study enrolled 90 patients: 11 in the monotherapy cohort and 79 in the combination cohort.

Among patients who underwent surgery, MPR occurred in 6 of 10 patients (60.0%) receiving monotherapy and 47 of 67 (70.1%) receiving the combination. In the combination cohort, the lower bound of the prespecified 80% confidence interval exceeded the historical MPR control rate of 41%, meeting the primary efficacy criterion. Grade 3 or higher treatment-related adverse events occurred in 4 of 11 patients (36.4%) in the monotherapy cohort and 24 of 79 (30.4%) in the combination cohort. No grade 3 or higher hemorrhage or treatment-related deaths were reported.

The findings suggest antitumor activity, but the noncomparative design and small monotherapy cohort limit comparisons between regimens. MPR is a pathological endpoint; the article states that overall survival and other planned outcomes are not reported in this manuscript. These results do not establish a survival benefit or support changing current treatment practice.