On August 14, 2025 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported that data from the Phase III HARMONi trial featuring the novel, potential first-in-class investigational bispecific antibody, ivonescimab, will be presented as part of the Presidential Symposium at the International Association for the Study of Lung Cancer’s (IASLC) 2025 World Conference on Lung Cancer (WCLC 2025) in Barcelona on Sunday, September 7, 2025, at 8:15am CET (2:15am ET) (Press release, Summit Therapeutics, AUG 14, 2025, View Source [SID1234655323]). This is the second consecutive year ivonescimab has been featured in the WCLC Presidential Symposium.
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HARMONi is a multiregional, double-blinded, placebo-controlled, Phase III study sponsored by Summit evaluating ivonescimab plus platinum-doublet chemotherapy compared to placebo plus platinum-doublet chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed after treatment with a 3rd generation EGFR tyrosine kinase inhibitor (TKI). This is a clinical setting with a patient population where PD-1 monoclonal antibodies have previously been unsuccessful in Phase III global clinical trials in showing either a progression-free survival (PFS) or overall survival (OS) benefit.
On May 30, 2025, we announced, via a press release, topline results from our multiregional, double-blinded, placebo-controlled, Phase III study, HARMONi. At the prespecified primary data analysis, ivonescimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), with a hazard ratio of 0.52 (95% CI: 0.41 – 0.66; p<0.00001). PFS was measured by blinded independent central radiology review committee (BICR) compared to placebo in combination with chemotherapy. Ivonescimab in combination with chemotherapy showed a positive trend in overall survival (OS) in the primary analysis without achieving a statistically significant benefit with a hazard ratio of 0.79 (95% CI: 0.62 – 1.01; p=0.057).
The trial results will be presented by Jonathan Goldman, MD, Professor of Medicine at UCLA in the Hematology/Oncology Division, UCLA Director of Clinical Trials in Thoracic Oncology, Associate Director of Early Drug Development, and Chair of University of California Lung Cancer Consortium.
About the WCLC 2025 Presidential Symposium Presentation
Presidential Symposium Presentation
Presentation Title: Ivonescimab vs Placebo Plus Chemo, Phase 3 in Patients with EGFR+ NSCLC Progressed with 3rd gen EGFR-TKI Treatment: HARMONi
Presenter: Jonathan Goldman, MD, Professor of Medicine at UCLA in the Hematology/Oncology Division
WCLC Presentation No.: PL02.12
Session Date & Time: Sunday, September 7, 2025, 8:15am CET (2:15am 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 (Free SITC Whitepaper), 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 (Free SITC Whitepaper), 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 clinical trial sites 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). Enrollment in HARMONi was completed in the second half of 2024, and top-line results were announced in May of 2025.
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.
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.