Summit Therapeutics Announces Completion of Enrollment in Its Phase III HARMONi Trial in 2L+ EGFRm NSCLC
Summit Therapeutics (NASDAQ: SMMT) has completed enrollment for its HARMONi Phase III clinical trial, evaluating ivonescimab plus platinum-doublet chemotherapy in EGFR-mutated NSCLC patients who progressed after 3rd generation EGFR TKI treatment. The study enrolled patients from North America, Europe, and China. Additionally, the FDA has granted Fast Track designation for ivonescimab in this indication, potentially expediting its development and review process.
The HARMONi trial's topline data is expected in mid-2025. The study's analysis will include patients from the HARMONi-A trial, which led to marketing authorization in China for ivonescimab on May 24, 2024. HARMONi is designed with dual primary endpoints of progression-free survival and overall survival.
Summit Therapeutics (NASDAQ: SMMT) ha completato l'arruolamento per il suo trial clinico di fase III HARMONi, che valuta ivonescimab in combinazione con chemioterapia a base di platino in pazienti con NSCLC mutato EGFR che hanno progredito dopo il trattamento con TKI EGFR di terza generazione. Lo studio ha arruolato pazienti dal Nord America, dall'Europa e dalla Cina. Inoltre, la FDA ha concesso la designazione Fast Track per ivonescimab in questa indicazione, potenzialmente accelerando il suo sviluppo e processo di revisione.
Si prevede che i dati principali del trial HARMONi siano disponibili a metà del 2025. L'analisi dello studio includerà pazienti del trial HARMONi-A, che ha portato all'autorizzazione alla commercializzazione in Cina per ivonescimab il 24 maggio 2024. HARMONi è progettato con due endpoint primari di sopravvivenza libera da progressione e sopravvivenza complessiva.
Summit Therapeutics (NASDAQ: SMMT) ha completado el reclutamiento para su ensayo clínico de fase III HARMONi, que evalúa ivonescimab más quimioterapia con doble platino en pacientes con NSCLC mutado por EGFR que progresaron después del tratamiento con TKI EGFR de tercera generación. El estudio reclutó pacientes de América del Norte, Europa y China. Además, la FDA ha otorgado la designación de Fast Track para ivonescimab en esta indicación, lo que podría acelerar su desarrollo y proceso de revisión.
Se espera que los datos preliminares del ensayo HARMONi se den a conocer a mediados de 2025. El análisis del estudio incluirá pacientes del ensayo HARMONi-A, que llevó a la autorización de comercialización en China para ivonescimab el 24 de mayo de 2024. HARMONi está diseñado con dos objetivos primarios de supervivencia libre de progression y supervivencia general.
Summit Therapeutics (NASDAQ: SMMT)는 HARMONi 3상 임상 시험의 등록을 완료하였으며, 이는 3세대 EGFR TKI 치료 후 진행된 EGFR 변이 NSCLC 환자에서 ivonescimab과 플래티넘 이중 화학요법을 평가합니다. 이 연구는 북미, 유럽 및 중국의 환자들을 등록했습니다. 또한 FDA는 이 적응증에 대해 ivonescimab에 패스트 트랙 지정을 부여했습니다, 이는 개발 및 검토 과정을 가속화할 수 있습니다.
HARMONi 시험의 주요 데이터는 2025년 중반에 예상되고 있습니다. 연구 분석에는 2024년 5월 24일 중국에서 ivonescimab의 마케팅 허가로 이어진 HARMONi-A 시험의 환자들이 포함될 것입니다. HARMONi는 무진행 생존 기간 및 전체 생존 기간이라는 두 가지 주요 목표로 설계되었습니다.
Summit Therapeutics (NASDAQ: SMMT) a achevé le recrutement pour son essai clinique de phase III HARMONi, évaluant ivonescimab en association avec une chimiothérapie double platine chez des patients atteints de NSCLC muté EGFR ayant progressé après un traitement par TKI EGFR de troisième génération. L'étude a recruté des patients en Amérique du Nord, en Europe et en Chine. De plus, la FDA a accordé la désignation Fast Track à ivonescimab pour cette indication, ce qui pourrait accélérer son développement et son processus d'examen.
Les données principales de l'essai HARMONi devraient être disponibles à mi-2025. L'analyse de l'étude inclura des patients de l'essai HARMONi-A, qui a conduit à l'autorisation de mise sur le marché en Chine pour ivonescimab le 24 mai 2024. HARMONi est conçu avec deux critères principaux de survie sans progression et de survie globale.
Summit Therapeutics (NASDAQ: SMMT) hat die Rekrutierung für seine HARMONi Phase-III-Studie abgeschlossen, die ivonescimab in Kombination mit einer Platin-Doppeltherapie bei EGFR-mutiertem NSCLC-Patienten bewertet, die nach einer Behandlung mit einem 3. Generation EGFR TKI fortgeschritten sind. Die Studie hat Patienten aus Nordamerika, Europa und China rekrutiert. Darüber hinaus hat die FDA ivonescimab für diese Indikation den Fast Track-Status vergeben, was die Entwicklung und den Überprüfungsprozess potenziell beschleunigen könnte.
Die wichtigsten Daten der HARMONi-Studie werden voraussichtlich mitte 2025 verfügbar sein. Die Analyse der Studie wird Patienten aus der HARMONi-A-Studie einbeziehen, die am 24. Mai 2024 zur Marktzulassung von ivonescimab in China führte. HARMONi ist mit zwei primären Endpunkten von progressionsfreier Überlebenszeit und Gesamtüberlebenszeit konzipiert.
- Completed enrollment for HARMONi Phase III trial, a multi-regional study
- FDA granted Fast Track designation for ivonescimab in 2L+ EGFRm NSCLC
- Marketing authorization received in China based on positive HARMONi-A trial data
- Potential to address an unmet medical need in NSCLC patients who progressed after EGFR TKI therapy
- Topline data from HARMONi trial not expected until mid-2025
- PD-1 monoclonal antibodies have previously been unsuccessful in this clinical setting
Insights
The completion of enrollment in Summit Therapeutics' HARMONi Phase III trial for ivonescimab is a significant milestone in the development of this potential treatment for EGFR-mutated NSCLC. This study addresses an important unmet need in patients who have progressed after 3rd generation EGFR TKI therapy, a setting where PD-1 inhibitors have previously failed.
The Fast Track designation granted by the FDA is particularly noteworthy, as it may accelerate the development and review process. This could potentially bring ivonescimab to market faster if the trial results are positive. The dual primary endpoints of progression-free survival and overall survival in HARMONi are robust measures that will provide comprehensive efficacy data.
Investors should note that while the enrollment completion and Fast Track designation are positive developments, the topline data expected in mid-2025 will be the critical factor in determining the drug's future. The earlier approval of ivonescimab in China based on the HARMONi-A trial data is encouraging, but global regulatory standards may differ.
From a financial perspective, the completion of enrollment in the HARMONi trial and the FDA's Fast Track designation are positive developments for Summit Therapeutics. These milestones potentially reduce the time and cost to bring ivonescimab to market, if successful.
The market opportunity for EGFR-mutated NSCLC treatments is substantial, given the high incidence and mortality rates of lung cancer. If ivonescimab demonstrates superiority over current standards of care, it could capture a significant market share.
Investors should consider that while these developments are promising, Summit still faces significant R&D expenses and regulatory hurdles before potential commercialization. The company's market cap of
FDA Grants Fast Track Designation for Ivonescimab in 2L+ EGFRm NSCLC
HARMONi Completed Enrollment for Summit’s First Sponsored Study Evaluating Ivonescimab
Topline data from the HARMONi Trial Is Expected in Mid-2025
“I would like to sincerely thank the investigators, site coordinators, Team Summit, and, most importantly, the patients around the world who are participating in the HARMONi study,” said Dr. Maky Zanganeh, Chief Executive Officer and President of Summit. “Completing enrollment in the first global study for ivonescimab is a credit to the growing belief in the potential for ivonescimab to make a significant difference in the lives of patients around the world.”
In addition, the
The FDA’s Fast Track designation is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. According to the FDA, the purpose is to get important new drugs to patients earlier. A drug that receives Fast Track designation is eligible for some of the following: more frequent meetings with the FDA to discuss the drug’s development plan, more frequent written communication from the FDA, and a rolling review process, allowing the sponsor to submit completed sections of its Biologic License Application (BLA) for review rather than every section at once, though the review by FDA typically begins when the entire application has been submitted. Per the FDA, once a drug receives Fast Track designation, early and frequent communication with the FDA is encouraged throughout the entire drug development and review process; the frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
“Completing enrollment in the HARMONi study represents another step towards our goal of bringing to patients a drug that is intended to improve the quality and potential duration of life for those facing serious unmet medical needs,” stated Robert W. Duggan, Chairman & Chief Executive Officer of Summit. “As our belief in the potential for ivonescimab to make a meaningful, positive difference continues to grow, we are pleased that the FDA has granted Fast Track designation for ivonescimab.”
As a reminder, the HARMONi analysis will include all patients from the HARMONi-A trial who previously received a 3rd generation TKI. HARMONi-A was a single-region, multi-center Phase III clinical trial evaluating ivonescimab plus platinum-doublet chemotherapy vs. placebo plus platinum-doublet chemotherapy with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI. HARMONi-A was sponsored by our collaboration partner, Akeso, Inc. (Akeso, HKEX Code: 9926.HK), with data generated and analyzed by Akeso. On May 24, 2024, our partner, Akeso, received marketing authorization in
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 TME 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 (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 (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 1,800 patients have been treated with ivonescimab in clinical studies globally.
Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multi-regional Phase III clinical trials, HARMONi and HARMONi-3, with a plan to initiate HARMONi-7 in early 2025.
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 designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC.
HARMONi-7 is a planned 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 (PD-L1 TPS >
In addition, Akeso has recently had positive read-outs in two single-region (
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 (PD-L1 TPS >
Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including
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
For more information, please visit https://www.smmttx.com and follow us on X @SMMT_TX.
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 Akeso Inc., the intended use of the net proceeds from the private placements, the Company's anticipated spending and cash runway, the therapeutic potential of the Company’s product candidates, the potential commercialization of the Company’s product candidates, the timing of initiation, completion and availability of data from clinical trials, the potential submission of applications for marketing approvals, potential acquisitions, statements about the previously disclosed At-The-Market equity offering program (“ATM Program”), the expected proceeds and uses thereof, and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the Company’s ability to sell shares of our common stock under the ATM Program, the conditions affecting the capital markets, general economic, industry, or political conditions, including the results of our evaluation of the underlying data in connection with the development and commercialization activities for ivonescimab, the outcome of discussions with regulatory authorities, including the Food and Drug Administration, the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials, the results of such trials, and their success, and global public health crises, that may affect timing and status of our clinical trials and operations, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials or preclinical studies will be indicative of the results of later clinical trials, whether business development opportunities to expand the Company’s pipeline of drug candidates, including without limitation, through potential acquisitions of, and/or collaborations with, other entities occur, expectations for regulatory approvals, laws and regulations affecting government contracts and funding awards, availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the "Risk Factors" section of filings that the Company makes with the Securities and Exchange Commission. Any change to our ongoing trials could cause delays, affect our future expenses, and add uncertainty to our commercialization efforts, as well as to affect the likelihood of the successful completion of clinical development of ivonescimab. Accordingly, readers should not place undue reliance on forward-looking statements or information. In addition, any forward-looking statements included in this press release represent the Company’s views only as of the date of this release and should not be relied upon as representing the Company’s views as of any subsequent date. The Company specifically disclaims any obligation to update any forward-looking statements included in this press release.
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.1
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.2
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.3
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.4
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.5
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.6
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.7
VEGF – Vascular Endothelial Growth Factor is a signaling protein that promotes angiogenesis.8
Summit Therapeutics and the Summit Therapeutics logo are trademarks of Summit Therapeutics Inc. Copyright 2024, Summit Therapeutics Inc. All Rights Reserved. |
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Source: Summit Therapeutics Inc.
FAQ
What is the HARMONi trial for Summit Therapeutics (SMMT)?
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