Clinical Summary:

• Design/Population: In the phase 3 HARMONi-6 trial, patients with previously untreated stage III-IV squamous non-small cell lung cancer were randomly assigned to receive ivonescimab plus chemotherapy or tislelizumab plus chemotherapy.
• Key Outcomes: Ivonescimab plus chemotherapy significantly improved overall survival and progression-free survival compared with tislelizumab plus chemotherapy.
• Clinical Relevance: These findings support ivonescimab plus chemotherapy as a potential new first-line standard of care for advanced squamous NSCLC.

Results from the phase 3 HARMONi-6 trial trial demonstrated that ivonescimab plus chemotherapy significantly improved overall survival (OS) compared with tislelizumab plus chemotherapy among previously untreated patients with advanced squamous non-small cell lung cancer (NSCLC). 

These results were presented by Shun Lu, MD, PhD, Shanghai Chest Hospital, Shanghai, China, in a plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this study, 532 patients with stage 3 to 4 squamous NSCLC were randomized 1:1 to receive either 20 mg/kg of ivonescimab or 200 mg of tislelizumab once every 3 weeks plus 175 mg/m² of paclitaxel and carboplatin AUC 5 for 4 cycles, followed by maintenance ivonescimab or tislelizumab. Patients were stratified by disease stage and PD-L1 tumor proportion score. The primary end point was progression-free survival (PFS), assessed via independent radiographic review committee. A key secondary end point was overall survival (OS). 

At a median follow-up of 21.4 months, median OS was 27.9 months in the ivonescimab plus chemotherapy arm and 23.7 months in the tislelizumab arm (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.50 to 0.87; P = .0017). The survival benefit was consistent across prespecified subgroups. Among patients with PD-L1 tumor proportion scores <1%, median OS was not reached in the ivonescimab arm and was 8.6 months in the tislelizumab arm. Among patients with PD-L1 tumor proportion scores ≥1%, median OS was not reached and 27.3 months, respectively. The safety profile was manageable and consistent with prior reports, with no new safety signals identified. 

“Ivonescimab plus chemotherapy is the first regimen to show clinical superiority over an active PD-1 inhibitor control arm in the first-line setting," concluded Dr Luo. 

Source:

Zhiwei C, Yang F, Luo Y, et al. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in previously untreated advanced squamous non–small cell lung cancer: Overall survival results of the phase 3 HARMONi-6 trial. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA4.