Chinese phase 3 trial shows a PD-1/VEGF bispecific antibody beats a PD-1 inhibitor on survival in squamous lung cancer

Ivonescimab, a bispecific antibody that blocks both PD-1 and VEGF, extended overall survival compared with the PD-1 inhibitor tislelizumab in patients with advanced squamous non-small-cell lung cancer, according to an interim analysis of the HARMONi-6 trial published in The Lancet on 27 June 2026. Both antibodies were given with chemotherapy. Median overall survival was 27.9 months in the ivonescimab group and 23.7 months in the tislelizumab group. The first author is Shun Lu of Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine. It is the first phase 3 evidence that a bispecific antibody can outperform an established checkpoint inhibitor on survival in this setting.

HARMONi-6, registered on ClinicalTrials.gov as NCT05840016, is a double-blind, randomised phase 3 trial run at 50 hospitals across China and funded by Akeso Biopharma, the Chinese company that developed ivonescimab. Eligible patients were aged 18 to 75 with previously untreated, pathologically confirmed, unresectable stage IIIB, IIIC or stage IV squamous non-small-cell lung cancer and an ECOG performance status of 0 or 1. Of 761 patients assessed for eligibility, 532 were randomised in a 1:1 ratio between 17 August 2023 and 21 January 2025, 266 to each arm. Of the participants, 494, or 93 per cent, were male, and the median age was 64 years, with an interquartile range of 59 to 69. Both arms received paclitaxel and carboplatin for four cycles, followed by maintenance monotherapy with the assigned antibody.

At the data cut-off of 27 February 2026, 204 deaths had occurred: 84, or 32 per cent, in the ivonescimab arm and 120, or 45 per cent, in the tislelizumab arm. Median follow-up was 21.4 months, with a 95 per cent confidence interval of 20.27 to 21.91. Median overall survival was 27.9 months with ivonescimab, 95 per cent CI 27.89 to not evaluable, against 23.7 months with tislelizumab, 95 per cent CI 20.11 to not evaluable. The hazard ratio for death was 0.66, 95 per cent CI 0.50 to 0.87, with a one-sided P value of 0.0017, crossing the pre-specified boundary of P less than 0.0049. The survival benefit was consistent across the key pre-specified subgroups. An earlier report from the same trial had already shown significantly longer progression-free survival with ivonescimab.

The interim analysis was triggered early, after 204 rather than the planned figure of roughly 225 overall survival events, in order to meet regulatory deadlines. On safety, grade 3 or higher treatment-related adverse events occurred in 184 of 266 patients, 69 per cent, given ivonescimab, compared with 156 of 265, 59 per cent, given tislelizumab. Grade 3 or higher haemorrhage, the expected risk of adding VEGF blockade in squamous histology, occurred in 7 of 266 patients, 3 per cent, versus 2 of 265, 1 per cent.

The choice of comparator sets this result apart. Tislelizumab is itself an approved PD-1 inhibitor, so the finding is a head-to-head win rather than a placebo-controlled one. Ivonescimab is already approved in China. The paper appears in The Lancet volume 407, issue 10548, pages 2620 to 2629, under DOI 10.1016/S0140-6736(26)00966-9, with PubMed identifier 42218899.

The global phase 3 programme, licensed to Summit Therapeutics, reported on 25 August 2026 that the HARMONi trial in EGFR-mutated non-squamous lung cancer had met its progression-free survival endpoint, with a median of 6.8 months versus 4.4 months and a hazard ratio of 0.52, 95 per cent CI 0.41 to 0.66, P less than 0.0001, across 114 centres in Asia, Europe and North America. A Biologics Licence Application has been filed in the United States with a PDUFA goal date of 14 November 2026. Confirmation of the survival signal outside China remains the key open question.