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.

Ivonescimab plus chemotherapy significantly improved overall survival (OS) compared with tislelizumab plus chemotherapy among patients with previously untreated advanced squamous non-small cell lung cancer (NSCLC), according to results from the phase 3 HARMONi-6 trial.

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

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

At a median follow-up of 21.4 months, ivonescimab plus chemotherapy significantly improved OS compared with tislelizumab plus chemotherapy. The median OS was 27.9 months (95% confidence interval [CI], 27.89 to not estimable) in the ivonescimab arm and 23.7 months (95% CI, 20.1 to not estimable) in the tislelizumab arm (hazard ratio [HR], 0.66; 95% 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 with ivonescimab compared with 18.6 months with tislelizumab (HR, 0.64; 95% CI, 0.43 to 0.96). Among patients with PD-L1 tumor proportion scores ≥1%, median OS was not reached and 27.3 months, respectively (HR, 0.68; 95% CI, 0.46 to 0.99).

Investigators reported that the safety profile of ivonescimab plus chemotherapy was manageable and consistent with prior reports, with no new safety signals identified.

“Ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared with tislelizumab plus chemotherapy in previously untreated patients with advanced sq-NSCLC,” concluded Dr Lu and coauthors. “Notably, ivonescimab plus chemotherapy is the first regimen to show clinical superiority over an active PD-1 inhibitor control arm in the first-line setting.”

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.