Ivonescimab shows OS benefit in NSCLC
By Agata Buczak
At a median follow-up of 21.4 months, ivonescimab plus chemotherapy significantly improved overall survival (OS) compared with an active PD‑1–based regimen in previously untreated advanced squamous non–small-cell lung cancer (NSCLC), according to phase 3 HARMONi‑6 results presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. Investigators reported this as “the first demonstration of superiority over an active PD‑1 inhibitor control arm in the first-line setting.”
Shun Lu (Shanghai Chest Hospital, China) presented the results, stating that “ivonescimab plus chemotherapy produced a statistically significant and clinically meaningful improvement in OS in this setting.” The study compared ivonescimab with an established PD‑1–based regimen rather than chemotherapy alone, enabling a direct assessment against a current first-line standard. Median OS was 27.9 months with ivonescimab plus chemotherapy versus 23.7 months with tislelizumab plus chemotherapy (hazard ratio, 0.66).
Subgroup analyses demonstrated a consistent survival benefit across PD‑L1 groups. In patients with PD‑L1 tumor proportion score below 1%, ivonescimab plus chemotherapy did not reach median OS, compared with 18.6 months with tislelizumab plus chemotherapy. In the PD‑L1–positive population, median OS was also not reached with ivonescimab compared with 27.3 months with the comparator.
HARMONi‑6 randomized 532 patients with previously untreated stage 3B–4 squamous NSCLC to receive ivonescimab or tislelizumab in combination with platinum-based chemotherapy, followed by maintenance therapy. The study had previously met its progression-free survival endpoint, which enabled hierarchical testing of OS.
Moreover, ivonescimab plus chemotherapy showed a manageable safety profile, broadly comparable to the PD‑1 inhibitor–based regimen. Grade ≥3 events were more frequent with ivonescimab (69.2% vs 58.9%), while rates of treatment discontinuation (5.3% vs 4.5%) and fatal events (3.8% vs 4.2%) were similar between groups. Grade ≥3 immune-related adverse events occurred in 14% of patients in both arms, and no new safety signals were identified.
Lu concluded that “ivonescimab plus chemotherapy produced a statistically significant and clinically meaningful improvement in OS in this setting,” and noted that further follow-up of HARMONi‑6 is ongoing.
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