Summit Therapeutics Inc., has filed a Biologics License Application (BLA) with the US FDA for ivonescimab, seeking approval for the bispecific antibody in combination with chemotherapy in epidermal growth factor receptor-mutated (EGFRm), locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC), in patients previously treated with a tyrosine kinase inhibitor. The FDA has issued a Prescription Drug User Fee Act (PDUFA) goal action date of November 14, 2026.
The filing is backed by data from the Phase III HARMONi study, which compared ivonescimab plus a platinum-doublet chemotherapy regimen to placebo plus chemotherapy in patients with EGFRm NSCLC who had been previously treated with a third-generation EGFR TKI. The combination reduced the risk of disease progression or death by 48% versus chemotherapy alone (PFS hazard ratio approximately 0.52), with median PFS of 6.8 months compared with 4.4 months in the control arm, and consistent benefit across key subgroups, including patients with brain metastases. Overall survival analyses showed a supportive benefit, with median OS of 16.8 months for ivonescimab plus chemotherapy versus 14.1 months for chemotherapy alone, corresponding to an OS hazard ratio of around 0.74 in the final analysis.
Discovered by Akeso and licensed to Summit for major markets outside Greater China, the programmed death-1 (PD-1)/vascular endothelial growth factor (VEGF) targeted bispecific antibody is designed to combine immune modulation (via PD-1 blockade) with anti-angiogenic effects in one molecule. Summit is hoping to offer the approximately 14,000 US NSCLC patients who progress post-TKI treatment a new therapeutic option.
Akeso secured a first China approval for ivonescimab plus chemotherapy for the HARMONi indication in June 2024, based on the HARMONi-A trial. A second China indication for ivonescimab as monotherapy in first-line treatment of PD-L1-positive, EGFR/ALK-negative NSCLC was issued in April 2025, based on HARMONi-2 results versus pembrolizumab.
In addition to HARMONi, Summit has started several multi-regional Phase III trials for various indications, including: the HARMONi-3 trial for ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy in first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression; HARMONi-7 for ivonescimab monotherapy compared to pembrolizumab monotherapy in first-line metastatic NSCLC with high PD-L1 expression; and HARMONi-GI3, for ivonescimab plus chemotherapy versus bevacizumab plus chemo in first-line unresectable metastatic colorectal carcinoma (CRC).