Summit Therapeutics Inc. announced that data from the Phase III HARMONi-6 trial will be highlighted during the prestigious Presidential Symposium at the upcoming European Society for Medical Oncology (ESMO) Congress 2025, taking place in Berlin, Germany, from October 17–21, 2025. The presentation is scheduled for Sunday, October 19, between 4:30 p.m. and 6:30 p.m. CET (10:30 a.m. to 12:30 p.m. EDT).
The HARMONi-6 trial, conducted in China and sponsored by Summit’s partner Akeso, Inc. (HKEX: 9926.HK), investigates ivonescimab, a novel, potential first-in-class investigational bispecific antibody. The study compares ivonescimab in combination with platinum-based chemotherapy against tislelizumab, a PD-1 inhibitor, in combination with the same chemotherapy backbone. The trial enrolled patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) regardless of PD-L1 expression status.
Key Findings from HARMONi-6
On April 23, 2025, Akeso released topline results from HARMONi-6. At a prespecified interim analysis, an Independent Data Monitoring Committee determined that the trial had met its primary endpoint of progression-free survival (PFS). According to blinded independent central radiology review (BICR), patients receiving ivonescimab plus chemotherapy achieved a statistically significant and clinically meaningful improvement in PFS compared to those treated with tislelizumab plus chemotherapy.
Importantly, the PFS benefit was observed in both PD-L1–positive and PD-L1–negative subgroups, suggesting broad potential utility for ivonescimab. Furthermore, the safety profile of the ivonescimab regimen was consistent with expectations, with no new safety signals identified in this large Phase III population.
The significance of these results is underscored by the fact that, prior to HARMONi-6, no Phase III clinical trial in NSCLC had demonstrated a statistically significant improvement over PD-(L)1 inhibitors combined with chemotherapy in a head-to-head comparison. This milestone highlights the potential of ivonescimab to reshape the treatment paradigm in squamous NSCLC.
The full trial results will be presented at ESMO 2025 by Dr. Shun Lu, MD, PhD, Chief of the Shanghai Lung Cancer Center at Shanghai Chest Hospital, Professor of Medicine at Shanghai Jiaotong University, and a leading authority in thoracic oncology. Dr. Lu also serves as associate editor for the Journal of Thoracic Oncology and Lung Cancer, and as editor for The Oncologist.
Broader Clinical Development of Ivonescimab
Summit continues to advance the clinical development of ivonescimab beyond HARMONi-6. The Company is currently enrolling patients in the HARMONi-3 study, a global, multi-regional Phase III trial sponsored by Summit. Unlike HARMONi-6, which is China-based, HARMONi-3 is being conducted with registrational intent in the United States and other Summit license territories.
HARMONi-3 is designed to evaluate ivonescimab plus chemotherapy versus pembrolizumab (Keytruda®) plus chemotherapy in patients with first-line metastatic NSCLC, including both squamous and non-squamous histologies. By positioning ivonescimab against pembrolizumab—the current global standard of care in many NSCLC settings—Summit aims to build on the encouraging results observed in HARMONi-6 and potentially broaden the availability of ivonescimab worldwide.
About the ESMO 2025 Presidential Symposium Presentation
Presidential Symposium Presentation
Presentation Title: Phase III Study of Ivonescimab plus chemotherapy versus Tislelizumab plus chemotherapy as First-line Treatment for advanced squamous non-small cell lung cancer (HARMONi-6)
Presenter: Dr.Shun Lu, MD, PhD, Chief of Shanghai Lung Cancer Center at Shanghai Chest Hospital
ESMO Presentation No.: Presidential Symposium 2, #3035
Session Date & Time: Sunday, October 19, 2025, 4:30pm – 6:30pm CET (10:30am – 12:30pm ET)
About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.
This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, SITC, 2023).
This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, SITC, 2023), is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.
Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 2,800 patients have been treated with ivonescimab in clinical studies globally.
Summit began its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. Additionally, in early 2025, the Company began enrolling patients in the United States for HARMONi-7.
HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib).
HARMONi-3 is a Phase III clinical trial which is intended to evaluate 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 which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.
In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6.
HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.
HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.
HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.
Akeso is actively conducting multiple Phase III clinical studies in settings outside of NSCLC, including biliary tract cancer, colorectal cancer, breast cancer, pancreatic cancer, small cell lung cancer, and head and neck cancer.
Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration (FDA) for the HARMONi clinical trial setting.
About Summit Therapeutics
Summit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs.
Summit was founded in 2003 and our shares are listed on the Nasdaq Global Market (symbol “SMMT”). We are headquartered in Miami, Florida, and we have additional offices in Menlo Park, California, and Oxford, UK.
For more information, please visit https://www.smmttx.com and follow us on X @SMMT_TX.
