Ivonescimab Monotherapy Decisively Beats Pembrolizumab Monotherapy Head-to-Head, Achieves Statistically Significant Superiority in PFS in First-Line Treatment of Patients with PD-L1 Positive NSCLC in China
Unprecedented: Ivonescimab Is the First Drug to Achieve Clinically Meaningful Benefit over Pembrolizumab in Randomized Phase III Clinical Trial in NSCLC
Monotherapy Ivonescimab Achieved Clinically Meaningful PFS Benefit in HARMONi-2 Trial Conducted by
PFS Improvement Was Observed Broadly in Patients Across Subgroups, including PD-L1 Low and PD-L1 High Expressing Tumors, Squamous and Non-Squamous Histologies
Full Data Set to be Presented at an Upcoming Major Medical Conference Planned for Later This Year
Conference Call to be Held at
At a prespecified interim analysis conducted by an independent Data Monitoring Committee, ivonescimab demonstrated a statistically significant and clinically meaningful improvement in PFS by blinded independent central radiology review committee (BICR) compared to pembrolizumab. The PFS benefit was demonstrated across clinical subgroups, including those with PD-L1 low expression (PD-L1 TPS 1-49%), PD-L1 high expression (PD-L1 TPS >50%), squamous and non-squamous histologies, as well as other high-risk patients.
There are no known Phase III clinical trials in NSCLC which have shown a statistically significant improvement compared to pembrolizumab in a head-to-head setting.
The Phase III HARMONi-2 study, along with the approval of ivonescimab in
“HARMONi-2 clearly demonstrates that ivonescimab is the next generation in PD-1 directed immunotherapy, and its potential to make a significant difference in the lives of patients with lung cancer and prospectively other tumors,” stated Dr.
“This is an historic moment for ivonescimab, Team Summit, our partners at
Conference Call
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About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories,
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 tumor microenvironment with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro.1 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,1 is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.
Ivonescimab was discovered by
The safety profile of ivonescimab is manageable and consistent with known risks for PD-1 and VEGF inhibiting drugs. In the first Phase III study to be presented at ASCO, “Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous NSCLC
HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to a placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC
HARMONi-3 is a Phase III clinical trial which is designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC.
Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including
About
Lung cancer is believed to impact approximately 600,000 people across
About
Summit was founded in 2003 and our shares are listed on the Nasdaq Global Market (symbol "SMMT"). We are headquartered in
For more information, please visit https://www.smmttx.com and follow us on X @summitplc.
Summit Forward-looking Statements
Any statements in this press release about the Company’s future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of the Company’s product candidates, entry into and actions related to the Company’s partnership with
Appendix: Glossary of Critical Terms Contained Herein
Affinity – Affinity is the strength of binding of a molecule, such as a protein or antibody, to another molecule, such as a ligand.
Avidity – Avidity is the accumulated strength of multiple binding interactions.
Angiogenesis – Angiogenesis is the development, formation, and maintenance of blood vessel structures. Without sufficient blood flow, tissue may experience hypoxia (insufficient oxygen) or lack of nutrition, which may cause cell death.6
Cooperative binding – Cooperative binding occurs when the number of binding sites on the molecule that can be occupied by a specific ligand (e.g., protein) is impacted by the ligand’s concentration. For example, this can be due to an affinity for the ligand that depends on the amount of ligand bound or the binding strength of the molecule to one ligand based on the concentration of another ligand, increasing the chance of another ligand binding to the compound.7
Immunotherapy – Immunotherapy is a type of treatment, including cancer treatments, that help a person’s immune system fight cancer. Examples include anti-PD-1 therapies.8
Intracranial - Within the cranium or skull.
PD-1 – Programmed cell Death protein 1 is a protein on the surface of T cells and other cells. PD-1 plays a key role in reducing the regulation of ineffective or harmful immune responses and maintaining immune tolerance. However, with respect to cancer tumor cells, PD-1 can act as a stopping mechanism (a brake or checkpoint) by binding to PD-L1 ligands that exist on tumor cells and preventing the T cells from targeting cancerous tumor cells.9
PD-L1 – Programmed cell Death Ligand 1 is expressed by cancerous tumor cells as an adaptive immune mechanism to escape anti-tumor responses, thus believed to suppress the immune system’s response to the presence of cancer cells.10
PD-L1 TPS – PD-L1 Tumor Proportion Score represents the percentage of tumor cells that express PD-L1 proteins.
PFS – Progression-Free Survival.
RANO –Response Assessment in Neuro-Oncology, the standard for assessing the response of a brain or spinal cord tumor to therapy.
SQ-NSCLC – Non-small cell lung cancer tumors of squamous histology.
T Cells – T cells are a type of white blood cell that is a component of the immune system that, in general, fights against infection and harmful cells like tumor cells.11
Tetravalent – A tetravalent molecule has four binding sites or regions.
Tumor Microenvironment – The tumor microenvironment is the ecosystem that surrounds a tumor inside the body. It includes immune cells, the extracellular matrix, blood vessels and other cells, like fibroblasts. A tumor and its microenvironment constantly interact and influence each other, either positively or negatively.12
VEGF – Vascular Endothelial Growth Factor is a signaling protein that promotes angiogenesis.13
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1 Zhong, et al, SITC 2023.
2
3 Schabath MB, Cote ML. Cancer Progress and Priorities:
4 About EGFR-Positive
5 Schabath MB, Cote ML. Cancer Progress and Priorities:
6 Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer. 2011 Dec;2(12):1097-105.
7 Stefan MI, Le Novère N. Cooperative binding. PLoS
8 US
9 Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020
10 Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020
11
12
13 Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer. 2011 Dec;2(12):1097-105.
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