Multiple Ivonescimab Data Sets from Phase III Studies to Be Highlighted at ELCC 2026
Summit Therapeutics Inc. has announced the presentation of multiple updated datasets for its investigational bispecific antibody, ivonescimab, at the European Lung Cancer Congress (ELCC) 2026, scheduled to take place in Copenhagen, Denmark. These presentations underscore the growing clinical interest in ivonescimab as a potential first-in-class therapy for patients with advanced non-small cell lung cancer (NSCLC), particularly those with challenging disease characteristics such as EGFR mutations and brain metastases.
The company will showcase three poster presentations featuring new and updated findings from its global Phase III clinical programs, including the HARMONi and HARMONi-2 studies. These data highlight ivonescimab’s therapeutic potential across multiple clinical endpoints, including intracranial efficacy and health-related quality of life (HRQoL), which are critical considerations in advanced lung cancer treatment.
Focus on Intracranial Efficacy in HARMONi Study
One of the most significant highlights of the presentations is the first poster, which focuses on intracranial anti-tumor activity in patients enrolled in the global Phase III HARMONi trial. This study evaluates ivonescimab in combination with chemotherapy versus chemotherapy alone in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have previously been treated with EGFR tyrosine kinase inhibitors (TKIs).
Brain metastases are a common and serious complication in advanced NSCLC, particularly among patients with EGFR mutations. Effective management of intracranial disease remains a major unmet medical need, making this dataset particularly important.
The results demonstrate that ivonescimab combined with chemotherapy significantly improved intracranial progression-free survival (PFS) compared to chemotherapy alone. Among patients with baseline brain metastases, intracranial PFS was extended to 10.1 months in the ivonescimab arm, compared to 6.5 months in the control arm. This corresponds to a hazard ratio (HR) of 0.53, indicating a 47% reduction in the risk of disease progression or death within the brain.
Importantly, benefits were also observed in patients without baseline central nervous system (CNS) metastases. In this subgroup, intracranial PFS reached 15.7 months with ivonescimab plus chemotherapy, compared to 11.6 months with chemotherapy alone (HR 0.72). These findings suggest that ivonescimab may provide both therapeutic and preventive benefits in managing intracranial disease.
Equally noteworthy is the safety profile observed in the study. Across subgroups defined by baseline brain metastasis status, no new safety signals were identified. This consistency reinforces the tolerability of ivonescimab in combination regimens, an essential factor for long-term treatment strategies.
Health-Related Quality of Life Outcomes in HARMONi
The second poster presentation shifts focus to patient-centered outcomes, specifically health-related quality of life. In advanced cancer settings, maintaining or improving quality of life is as important as extending survival, given the significant symptom burden and treatment-related side effects experienced by patients.
This analysis from the HARMONi study evaluates HRQoL in patients receiving ivonescimab plus chemotherapy compared to those receiving chemotherapy alone. The study includes patients who had previously been treated with EGFR TKIs, representing a population with limited treatment options and often diminished quality of life.
Although detailed numerical outcomes are not provided in the summary, the inclusion of HRQoL as a key endpoint reflects a broader shift in oncology toward holistic patient care. By assessing factors such as physical functioning, symptom burden, and overall well-being, the study aims to determine whether the clinical benefits of ivonescimab translate into meaningful improvements in patients’ daily lives.
These data are expected to provide valuable insights into how ivonescimab impacts not just disease progression but also the lived experience of patients undergoing treatment.
Comparative Quality of Life in HARMONi-2 Study
The third poster presentation introduces findings from the HARMONi-2 trial, a randomized, double-blind Phase III study conducted in China. This study compares ivonescimab monotherapy to pembrolizumab monotherapy in patients with PD-L1 positive, locally advanced or metastatic NSCLC.
Pembrolizumab, a widely used immune checkpoint inhibitor, has become a standard of care for patients with PD-L1 positive tumors. Therefore, demonstrating comparable or superior outcomes against this benchmark is a significant milestone for any investigational therapy.
The HARMONi-2 study focuses on health-related quality of life outcomes, offering a comparative perspective between the two treatments. Patients enrolled in this study had tumors expressing PD-L1, making them suitable candidates for immunotherapy-based approaches.
All data for HARMONi-2 were collected and analyzed by Akeso Inc., Summit’s collaboration and licensing partner. The inclusion of HRQoL endpoints in this head-to-head comparison highlights the importance of evaluating not only clinical efficacy but also the overall patient experience when selecting treatment options.
While efficacy data from this study are not detailed in the announcement, the HRQoL findings are expected to contribute to a more comprehensive understanding of ivonescimab’s value proposition relative to established therapies.
Broader Implications for NSCLC Treatment
The data being presented at ELCC 2026 reflect the expanding clinical development program for ivonescimab and its potential role in addressing unmet needs in NSCLC. As a bispecific antibody, ivonescimab is designed to target multiple pathways involved in tumor growth and immune evasion, offering a novel mechanism of action compared to traditional therapies.
The consistent focus across all three presentations—intracranial efficacy and quality of life—underscores the evolving priorities in oncology. While extending survival remains a primary goal, there is increasing recognition of the need to manage complex disease manifestations, such as brain metastases, and to preserve patients’ quality of life during treatment.
The HARMONi and HARMONi-2 studies collectively explore ivonescimab’s utility across different patient populations, including those with EGFR mutations and those with PD-L1 positive tumors. This broad applicability could position ivonescimab as a versatile treatment option in the NSCLC landscape.
Timing and Presentation Details
All three posters will be presented on Friday, March 27, during a dedicated session at ELCC 2026, from 1:00 to 2:00 pm Central European Time. The conference, held in Copenhagen, serves as a key platform for the global oncology community to share the latest advancements in lung cancer research and treatment.
The simultaneous presentation of multiple datasets highlights the depth of evidence being generated for ivonescimab and signals growing confidence in its clinical potential.
Conclusion
The upcoming presentations at ELCC 2026 mark an important milestone for ivonescimab and its development in advanced NSCLC. The data span critical areas of clinical need, including improved control of brain metastases and the impact of treatment on patients’ quality of life.
Findings from the HARMONi study suggest that ivonescimab, when combined with chemotherapy, may significantly enhance intracranial outcomes without introducing new safety concerns. Meanwhile, quality of life analyses from both HARMONi and HARMONi-2 provide a more comprehensive view of the therapy’s benefits from the patient perspective.
As the oncology field continues to evolve toward more personalized and patient-centered care, therapies like ivonescimab that demonstrate both clinical efficacy and quality of life benefits may play an increasingly important role. The data presented at ELCC 2026 will contribute to ongoing discussions about optimizing treatment strategies for patients with advanced NSCLC and may help shape future standards of care.
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 outside of Summit’s license territories, 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. By design, 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 is intended to 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. We believe ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, iScience, 2025). 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, iScience, 2025) increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, side effects, and safety profiles associated with prior approved drugs to these targets.
Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently utilized 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.
There are currently 15 Phase III clinical studies that are either announced, ongoing, or have been completed studying ivonescimab, four of which are Summit-sponsored global studies, one of which is a multiregional study sponsored by a cooperative group, and ten of which are being or have been conducted in China by Akeso. Summit began its clinical development of ivonescimab in NSCLC, commencing enrollment in 2023 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 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 were previously treated with a 3rd generation EGFR TKI (e.g., osimertinib). Detailed results of the study were provided in September 2025, and a Biologics License Application (BLA) was submitted to the United States Food and Drug Administration (FDA) for marketing authorization, which the FDA accepted for filing in January 2026; the goal Prescription Drug User Fee Act (PDUFA) date is November 14, 2026.
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.
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.
Also including Summit’s license territories, a Phase III study is planned to be conducted by GORTEC, a cooperative group dedicated to Head and Neck Oncology, in recurrent / metastatic head and neck squamous cell carcinoma (r/m HNSCC). ILLUMINE is a three-arm Phase III clinical trial which is intended to evaluate ivonescimab monotherapy, as well as ivonescimab in combination with ligufalimab, Akeso’s proprietary anti-CD47 monoclonal antibody, compared to monotherapy pembrolizumab in patients with PD-L1 positive r/m HNSCC.
In addition, Akeso has recently 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, including a statistically significant overall survival benefit in HARMONi-A with a manageable safety profile in each study.
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, triple-negative breast cancer, head and neck squamous cell carcinoma, small cell lung cancer, colorectal cancer, and pancreatic 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 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 Palo Alto, California, Princeton, New Jersey, Dublin, Ireland, and Oxford, UK.
