Ivonescimab Plus Chemotherapy Shows Improving OS Trend in EGFRm NSCLC: HARMONi Trial Follow-Up

09/07/2025 – 03:30 AM

With Longer-Term Follow-Up of Western Patients, Ivonescimab Plus Chemotherapy Demonstrated Improving Global OS Trend with Nominal p-value of 0.0332 vs. Chemotherapy Alone; North American Patients’ OS HR=0.70

Consistent Median Overall Survival Observed in Western, Asian Patients in Longer-Term Follow-Up Analysis of Western Patients Presented at Presidential Symposium at WCLC 2025

Conference Call to be Held at 8:00am ET on Monday, September 8, 2025

MIAMI–(BUSINESS WIRE)–Summit Therapeutics Inc. (NASDAQ: SMMT) (“Summit,” “we,” or the “Company”) unveiled compelling data from its Phase III HARMONi trial, spotlighting ivonescimab, an investigational bispecific antibody with potential first-in-class status. The findings were a highlight 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, Spain. This announcement has drawn attention as the biopharmaceutical firm positions itself in the competitive landscape of lung cancer therapeutics.

The HARMONi presentation, titled Ivonescimab vs Placebo Plus Chemo, Phase 3 in Patients with EGFR+ NSCLC Progressed with 3rd gen EGFR-TKI Treatment: HARMONi, centered on the efficacy of ivonescimab combined with platinum-doublet chemotherapy, compared against a control group receiving placebo plus platinum-doublet chemotherapy. The study targeted patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who had experienced disease progression after treatment with a 3rd generation EGFR tyrosine kinase inhibitor (TKI). This patient population presents a significant unmet need, as PD-1 monoclonal antibodies have previously faltered in Phase III global clinical trials, failing to demonstrate a progression-free survival (PFS) or overall survival (OS) advantage — the key endpoints of this study. The failure of PD-1 inhibitors in this specific setting underscores the need for novel approaches like ivonescimab. The study’s rigorous design aims to address this therapeutic gap.

The trial results were presented by Dr. Jonathan Goldman, Professor of Medicine at UCLA in the Hematology/Oncology Division.

Clinically Meaningful Efficacy

Initial findings indicated a positive trend in OS, although statistical significance was not met in the primary analysis. The hazard ratio was 0.79 (95% CI: 0.62 – 1.01; p=0.057), just shy of the pre-determined p-value of 0.0448 required for statistical significance. Median overall survival reached 16.8 months for patients on ivonescimab plus chemotherapy, compared to 14.0 months for those receiving placebo plus chemotherapy. The company noted that the median follow-up for western patients (9.2 months) was less than the median overall survival, prompting continued monitoring of these patients for long-term outcomes, a strategic move to maximize the data set.

A subsequent analysis in September 2025, incorporating longer-term follow-up data from western patients (median follow-up of 13.7 months), revealed a consistent hazard ratio alongside an improved nominal p-value (HR=0.78; 95% CI: 0.62 – 0.98; nominal p=0.0332). Median OS remained consistent across both arms. Specifically, western patients receiving ivonescimab exhibited a median OS of 17.0 months versus 14.0 months for placebo (HR=0.84). Notably, in North American patients, the median OS in the ivonescimab arm had not yet been reached, compared to 14.0 months in the placebo arm (HR=0.70), showcasing the drug’s potential in this demographic. The improved hazard ratios across western, North American, and European regions individually from the primary analysis suggest a trend toward greater efficacy with extended treatment duration. Subgroup analysis revealed consistent benefits.

Progression-free survival (PFS) also demonstrated a significant and clinically meaningful improvement with ivonescimab plus chemotherapy, with a hazard ratio of 0.52 (95% CI: 0.41 – 0.66; p

Longer-term PFS follow-up of all western patients (minimum six months) showed consistent improvement (HR 0.57; 95% CI: 0.46 – 0.71). This was observed across western and Asian patients, as well as those with PD-L1 positive or negative tumors. The company’s strategic focus on longer follow-up periods seems to be yielding valuable insights.

Overall response rates favored the ivonescimab arm (45%) compared to placebo (34%), with a longer median duration of response (7.6 months vs. 4.2 months). These figures suggest a more robust and sustained clinical benefit.

“The HARMONi study’s positive results highlight ivonescimab’s global potential and its potential benefits for patients worldwide,” said Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit. “Collaboration with the US FDA has been instrumental in expanding this trial into a multiregional setting, bringing ivonescimab closer to patients in need.”

Manageable, Consistent Safety Profile

The safety profile of ivonescimab plus chemotherapy remained acceptable and consistent with prior studies. Tolerability was good, with no new safety signals and comparable rates of discontinuation and death between arms. Discontinuation due to treatment-related adverse events (TRAEs) occurred in 7.3% of ivonescimab patients versus 5.0% of placebo patients. Fatal TRAEs were seen in 1.8% of the ivonescimab arm and 2.3% of the chemotherapy alone arm. Common TRAEs included anemia and decreases in white blood cell count, neutrophil count, and platelet count. The near-absence of Grade 3 or higher hemorrhage events (

“HARMONi and upcoming readouts from HARMONi-2 and HARMONi-6 uniquely position ivonescimab to reshape cancer treatment globally,” stated Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit. This optimistic outlook hinges on the potential of ivonescimab to address unmet needs in NSCLC treatment, particularly after failure of first-line TKIs or PD-1 inhibitors. The company plans to leverage these results in future discussions with regulatory agencies. Investors are closely watching for updates on regulatory pathways and potential commercialization strategies.

Conference Call

Summit Therapeutics Inc. will host a conference call and live webcast to discuss recent updates related to ivonescimab, including data released at WCLC, on Monday, September 8, 2025 at 8:00am ET.

An archived edition of the webcast will be available on our website later in the day on Monday.

About Ivonescimab

Ivonescimab (SMT112 in North America, South America, Europe, the Middle East, Africa, and Japan; AK112 in China and Australia) is a novel bispecific antibody combining PD-1 blockade with anti-VEGF activity. The molecule’s design allows cooperative binding to both targets, favoring tumor tissue accumulation over healthy tissue, potentially enhancing efficacy and reducing side effects. The strategy of combining immunotherapy and anti-angiogenesis in a single molecule has been validated by this trial and may lead to a new paradigm in treating NSCLC.

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 initiated its clinical development of ivonescimab in NSCLC in 2023 , commencing enrollment 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.

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.

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