Miami, Florida — January 29, 2026 — Leads & Copy — Summit Therapeutics Inc. (NASDAQ: SMMT) announced that the U.S. Food & Drug Administration (FDA) has accepted for filing its Biologics License Application (BLA) seeking approval for ivonescimab in combination with chemotherapy for patients with epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) post-tyrosine kinase inhibitor (TKI) therapy. The FDA has set a Prescription Drug User Fee Act (PDUFA) goal action date of November 14, 2026.
The BLA submission was based on the Phase III HARMONi trial results. The trial evaluated ivonescimab plus platinum-doublet chemotherapy compared to placebo plus platinum-doublet chemotherapy in patients with EGFR-mutated, locally advanced or metastatic NSCLC previously treated with a 3rd generation EGFR TKI.
The FDA plans a complete review of the application in accordance with draft guidance, Good Review Management Principles and Practices for New Drug Applications and Biologics License Applications. The review includes planned mid-cycle and wrap-up meetings, and proposed labeling, before the PDUFA date, pending major deficiencies not identified during the review.
Ivonescimab, also known as SMT112 in Summit’s license territories (North America, South America, Europe, the Middle East, Africa, and Japan) and AK112 outside those territories, is an investigational bispecific antibody. It combines immunotherapy via PD-1 blockade with anti-angiogenesis effects by blocking VEGF in a single molecule.
The design of ivonescimab allows cooperative binding to its targets, displaying higher affinity to PD-1 in the presence of VEGF. Summit believes that the higher expression of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) compared to normal tissue differentiates ivonescimab. The tetravalent structure of the molecule enables higher avidity in the TME (Zhong, et al, iScience, 2025), potentially directing ivonescimab to tumor tissue versus healthy tissue.
The intent of the design and a half-life of 6 to 7 days after the first dose (Zhong, et al, iScience, 2025), increasing to approximately 10 days at steady-state dosing, aim to improve efficacy thresholds, side effects, and safety profiles compared to prior drugs targeting these factors.
Akeso Inc. (HKEX Code: 9926.HK) engineered ivonescimab, which is currently in multiple Phase III clinical trials. Over 4,000 patients have been treated with ivonescimab in clinical studies globally, and over 60,000 patients when considering those treated in a commercial setting in China, as noted by Akeso.
Currently, there are 14 Phase III clinical studies ongoing or completed studying ivonescimab, with ten conducted in China by Akeso and four Summit-sponsored global studies. Summit began clinical development of ivonescimab in NSCLC in 2023, commencing enrollment in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. In 2025, the company began enrolling patients in HARMONi-7. Summit expanded its Phase III clinical development program into CRC in the fourth quarter of 2025 by initiating enrollment in HARMONi-GI3.
HARMONi is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC previously treated with a 3rd generation EGFR TKI. Detailed study results were provided in September 2025, and a BLA was submitted to the FDA for marketing authorization with a PDUFA date of November 14, 2026.
HARMONi-3 is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression.
HARMONi-7 is a Phase III clinical trial evaluating ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.
HARMONi-GI3 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC.
Akeso has also had positive read-outs in three single-region (China), randomized Phase III clinical trials, HARMONi-A, HARMONi-2, and HARMONi-6, for ivonescimab in NSCLC. These include a statistically significant overall survival benefit in HARMONi-A with a manageable safety profile in each study.
Ivonescimab is an investigational therapy not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. It was initially approved for marketing authorization in China in May 2024 and was granted Fast Track designation by the US FDA for the HARMONi clinical trial setting.
Summit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of therapies intended to improve quality and duration of life and resolve unmet medical needs.
Summit was founded in 2003, and its shares are listed on the Nasdaq Global Market (symbol “SMMT”). It is headquartered in Miami, Florida, with additional offices in Menlo Park, California, and Oxford, UK.
Source: Summit Therapeutics
