Promising Anti-Tumor Activity and Safety of Ivonescimab in Combination Therapies in CRC, TNBC, and HNSCC Featured at ESMO 2024
Summit Therapeutics (NASDAQ: SMMT) presented promising data for ivonescimab, a novel bispecific antibody, at ESMO 2024. Phase II studies showed encouraging results in colorectal cancer (CRC), triple-negative breast cancer (TNBC), and head and neck squamous cell carcinoma (HNSCC).
In CRC, ivonescimab plus chemotherapy achieved an 81.8% overall response rate and 100% disease control rate. For TNBC, the combination showed a 72.4% overall response rate and 9.3-month median progression-free survival. In HNSCC, ivonescimab alone or with ligufalimab demonstrated response rates of 30% and 60%, respectively.
These results support Summit's plans to expand ivonescimab's clinical development beyond non-small cell lung cancer. The drug's safety profile was generally manageable across all studies.
Summit Therapeutics (NASDAQ: SMMT) ha presentato dati promettenti per ivonescimab, un nuovo anticorpo bispecifico, all'ESMO 2024. Gli studi di fase II hanno mostrato risultati incoraggianti nel cancro colorettale (CRC), nel cancro al seno triplo negativo (TNBC) e nel carcinoma a cellule squamose della testa e del collo (HNSCC).
Nel CRC, ivonescimab in combinazione con la chemioterapia ha raggiunto un tasso di risposta complessivo dell'81,8% e un tasso di controllo della malattia del 100%. Per il TNBC, la combinazione ha mostrato un tasso di risposta complessivo del 72,4% e una sopravvivenza libera da progressione mediana di 9,3 mesi. Nel HNSCC, ivonescimab da solo o con ligufalimab ha dimostrato tassi di risposta del 30% e del 60%, rispettivamente.
Questi risultati supportano i piani di Summit di espandere lo sviluppo clinico di ivonescimab oltre il cancro polmonare non a piccole cellule. Il profilo di sicurezza del farmaco è stato generalmente gestibile in tutti gli studi.
Summit Therapeutics (NASDAQ: SMMT) presentó datos prometedores sobre ivonescimab, un nuevo anticuerpo bispecífico, en el ESMO 2024. Los estudios de fase II mostraron resultados alentadores en cáncer colorrectal (CRC), cáncer de mama triple negativo (TNBC) y carcinoma de células escamosas de cabeza y cuello (HNSCC).
En CRC, ivonescimab más quimioterapia logró una tasa de respuesta general del 81,8% y una tasa de control de la enfermedad del 100%. Para TNBC, la combinación mostró una tasa de respuesta general del 72,4% y una mediana de supervivencia libre de progresión de 9,3 meses. En HNSCC, ivonescimab solo o con ligufalimab demostró tasas de respuesta del 30% y del 60%, respectivamente.
Estos resultados respaldan los planes de Summit para expandir el desarrollo clínico de ivonescimab más allá del cáncer de pulmón no microcítico. El perfil de seguridad del fármaco fue generalmente manejable en todos los estudios.
서밋 테라퓨틱스 (NASDAQ: SMMT)가 ESMO 2024에서 새로운 이중 특이 항체인 이보네시맙에 대한 유망한 데이터를 발표했습니다. 2상 연구에서 대장암 (CRC), 삼중 음성 유방암 (TNBC), 두경부 편평세포암 (HNSCC)에서 유망한 결과를 보여주었습니다.
CRC에서는 이보네시맙과 항암 화학요법의 병용으로 전체 반응률이 81.8%에 달하고, 질병 조절률은 100%였습니다. TNBC의 경우, 병용 요법이 72.4%의 전체 반응률과 9.3개월의 중앙 무진행 생존 기간을 보여주었습니다. HNSCC에서는 이보네시맙 단독 또는 리구팔리맙과 병용 시 각각 30%와 60%의 반응률을 보였습니다.
이러한 결과는 서밋이 이보네시맙의 임상 개발을 비소세포 폐암 이외의 분야로 확장할 계획을 뒷받침합니다. 모든 연구에서 약물의 안전성 프로필은 일반적으로 관리 가능한 수준이었습니다.
Summit Therapeutics (NASDAQ: SMMT) a présenté des données prometteuses sur l'ivonesimab, un nouvel anticorps bispécifique, lors de l'ESMO 2024. Les études de phase II ont montré des résultats encourageants dans le cancer colorectal (CRC), le cancer du sein triple négatif (TNBC) et le carcinome à cellules squameuses de la tête et du cou (HNSCC).
Dans le CRC, l'ivonesimab associé à la chimiothérapie a atteint un taux de réponse global de 81,8 % et un taux de contrôle de la maladie de 100 %. Pour le TNBC, la combinaison a montré un taux de réponse global de 72,4 % et une survie sans progression médiane de 9,3 mois. Dans le HNSCC, l'ivonesimab seul ou avec le ligufalimab a démontré des taux de réponse respectifs de 30 % et 60 %.
Ces résultats soutiennent les plans de Summit d'élargir le développement clinique de l'ivonesimab au-delà du cancer du poumon non à petites cellules. Le profil de sécurité du médicament était généralement gérable dans toutes les études.
Summit Therapeutics (NASDAQ: SMMT) präsentierte vielversprechende Daten zu Ivonesimab, einem neuartigen bispezifischen Antikörper, auf dem ESMO 2024. Phase-II-Studien zeigten ermutigende Ergebnisse bei kolorektalem Krebs (CRC), dreifach negativem Brustkrebs (TNBC) und Plattenepithelkarzinom des Kopf-Hals-Bereichs (HNSCC).
Im CRC erreichte die Kombination von Ivonesimab und Chemotherapie eine Gesamtansprechrate von 81,8 % und eine Krankheitskontrollrate von 100 %. Bei TNBC zeigte die Kombination eine Gesamtansprechrate von 72,4 % und ein medianes progressionsfreies Überleben von 9,3 Monaten. Bei HNSCC zeigten Ivonesimab allein oder in Kombination mit Ligufalimab Ansprechraten von 30 % bzw. 60 %.
Diese Ergebnisse unterstützen die Pläne von Summit, die klinische Entwicklung von Ivonesimab über nicht-kleinzelliges Lungenkarzinom hinaus auszudehnen. Das Sicherheitsprofil des Medikaments war in allen Studien im Allgemeinen handhabbar.
- High overall response rates in CRC (81.8%) and TNBC (72.4%) trials
- 100% disease control rate in both CRC and TNBC studies
- Promising efficacy in HNSCC with 60% response rate when combined with ligufalimab
- Manageable safety profile across all studies with low discontinuation rates
- Potential expansion of ivonescimab's clinical development into multiple solid tumor types
- sample sizes in Phase II studies (22-30 patients per arm)
- Median progression-free survival not reached in some arms, indicating immature data
- Higher rates of serious treatment-related adverse events in some study arms (up to 30% in TNBC)
Insights
The data presented at ESMO 2024 for ivonescimab in combination therapies shows promising results across multiple solid tumor types. In metastatic MSS colorectal cancer, the combination with FOLFOXIRI chemotherapy achieved an impressive
This clinical data release is positive for Summit Therapeutics and its development of ivonescimab. The promising efficacy across multiple tumor types expands the potential market opportunity beyond lung cancer, which could significantly increase the drug's commercial value if approved. The high response rates and disease control rates observed are competitive with existing standards of care in these indications. However, investors should note these are early Phase II results from China and larger global studies will be needed to confirm the findings. The company's intention to explore further clinical development in additional solid tumors is encouraging for long-term growth prospects. While financial impact is still years away, positive clinical data typically supports biotech valuations and can attract potential partners or acquirers.
As an oncologist, I find these results intriguing, particularly in difficult-to-treat cancers. The 100% disease control rate in MSS colorectal cancer is noteworthy, as these patients typically have treatment options. In TNBC, the
Two Oral Presentations Featured Updated Ivonescimab Data from Phase II Studies in CRC and TNBC in Addition to Poster Presentation on HNSCC
Encouraging Phase II Data Supports the Continuing Expansion of the Clinical Development of Ivonescimab Outside of Metastatic Non-Small Cell Lung Cancer
Based on the results of these Phase II data sets as well as data announced earlier in 2024, including early-stage non-small cell lung cancer and biliary tract cancer, Summit intends to explore further clinical development of ivonescimab in solid tumor settings outside of metastatic non-small cell lung cancer, the Company’s current area of focus in its Phase III clinical trials.
Metastatic MSS Colorectal Cancer
The first oral presentation was presented by Dr. Yanhong Deng, Sun Yat-Sen University. The presentation was entitled, The efficacy and safety of ivonescimab with or without ligufalimab in combination with FOLFOXIRI (chemotherapy) as first-line treatment for metastatic CRC, presenting the current data from AK112-206, included data from this single-region (
The study was designed to assess patients who were randomly assigned to receive ivonescimab plus FOLFOXIRI with or without ligufalimab (anti-CD47 monoclonal antibody). Note that ligufalimab, or AK117, is Akeso’s proprietary, investigational product that is not approved by any regulatory authority, and to which Summit does not have any license or ownership rights.
As of February 29, 2024, 22 patients received ivonescimab plus FOLFOXIRI (“Group A” with median follow-up time of 9 months); 18 patients received ivonescimab plus ligufalimab plus FOLFOXIRI (“Group B” with median follow-up time of 9.6 months).
|
Ivonescimab + Chemo (Group A) (n = 22) |
Ivonescimab + Ligufalimab + Chemo (Group B) (n = 18)a |
Overall response rate |
( |
( |
Disease control rate |
( |
( |
Median PFS |
NR |
NR |
9-month PFS rate |
( |
( |
Serious TRAE |
|
|
TRAEs Leading to Permanent Discontinuation |
0 |
|
a As of data cutoff, one patient in Group B had not yet had a post-baseline tumor assessment; Group B response and control rates based on n=17.
All patients in both Group A and Group B experienced a reduction in their tumor burden compared to their baseline tumor assessment. The overall response rate and the disease control rate for the 39 patients who had a least one post-baseline tumor assessment was
The safety profile in this Phase II study was acceptable and manageable. No patients receiving ivonescimab plus FOLFOXIRI and one patient receiving ivonescimab plus ligufalimab plus FOLFOXIRI permanently discontinued drug treatment due to treatment-related adverse events. The most common TRAEs were anemia, proteinuria, white blood cell count decreases, and neutrophil count decreases in this Phase II data set.
Advanced Triple Negative Breast Cancer
The second oral presentation was presented by Dr. Xiaojia Wang, Zhejiang Cancer Hospital. The presentation was entitled, The safety and efficacy of ivonescimab in combination with chemotherapy as first-line (1L) treatment for triple-negative breast cancer (TNBC), presenting the current data from AK117-203, included data from this single-region (
The results presented were from the portion of the study intended to assess patients who received ivonescimab plus chemotherapy (either paclitaxel or nab-paclitaxel) with locally advanced or metastatic TNBC.
As of May 31, 2024, 30 patients received ivonescimab plus chemotherapy with median follow-up time of 10.2 months. Sixty percent of patients had previously received taxane-based chemotherapy in either the neoadjuvant or adjuvant setting in this Phase II data set.
|
Overall (n = 30)a |
Overall response rate |
|
Disease control rate |
|
Median PFS |
9.3 months
( |
Serious TRAE |
|
TRAEs Leading to Permanent Discontinuation |
0 |
|
PD-L1 CPS >10 (n = 6) |
PD-L1 CPS <10 (n = 24)a |
PD-L1 CPS <1 (n = 16)a |
Overall response rate |
|
|
|
Disease control rate |
|
|
|
Median PFS |
NR (5.36, NE) |
9.3 months (5.55, NE) |
9.3 months (5.26, NE) |
a As of data cutoff, one patient with a PD-L1 CPS expression of 0 had not yet had a post-baseline tumor assessment; Overall patients, PD-L1 CPS <10, and PD-L1 CPS <1 response and control rates based on n=29, n=23, and n=15, respectively.
All patients experienced a reduction in their tumor burden compared to their baseline tumor assessment. The overall response rate and the disease control rate for the 29 patients who had at least one post-baseline tumor assessment were
The safety profile in this Phase II study was acceptable and manageable. No patients receiving ivonescimab plus chemotherapy permanently discontinued drug treatment due to treatment-related adverse events. The most common TRAEs were white blood cell count decreases, ALT increases, alopecia, AST increases, and neutrophil count decreases in this Phase II data set.
Recurrent / Metastatic Head and Neck Squamous Cell Carcinoma
The third data presentation was a poster from Dr. Xiaozhong Chen, et al. The poster was entitled, Evaluation of the safety and efficacy of ivonescimab in combination with ligufalimab (anti-CD47) as first-line treatment for PD-L1 positive recurrent/metastasis HNSCC, presenting current data from a portion of AK117-201. The data is from a single-region (
The results presented were from the portion of the study intended to assess patients who received ivonescimab with or without ligufalimab (anti-CD47) with PD-L1 positive, locally advanced or metastatic recurrent / metastatic head and neck squamous cell carcinoma.
As of March 19, 2024, 10 patients received ivonescimab (median follow-up: 3.3 months) and 20 patients received ivonescimab plus ligufalimab (median follow-up 4.1 months). Four of 10 patients receiving ivonescimab had a PD-L1 CPS of 1-20; nine of 20 patients administered ivonescimab plus ligufalimab had a PD-L1 CPS of 1-20; the remaining patients in each arm had a PD-L1 CPS >20.
|
Ivonescimab (n=10) |
Ivonescimab + Ligufalimab (n = 20) |
Overall response rate |
|
|
Disease control rate |
|
|
Median PFS |
5.0 months |
7.1 months |
6-month PFS rate |
NR |
|
Serious TRAE |
0 |
|
TRAEs Leading to Permanent Discontinuation |
0 |
0 |
The overall response rate and the disease control rate for the 30 patients was
The safety profile in this Phase II study was acceptable and manageable. No patients receiving ivonescimab or ivonescimab plus ligufalimab in this data set permanently discontinued drug treatment due to treatment-related adverse events. The most common TRAEs in this Phase II data set were proteinuria, dermatitis acneiform (each observed in both arms), and hypothyroidism (observed only in the ivonescimab plus ligufalimab arm).
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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1 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
2 Stefan MI, Le Novère N. Cooperative binding. PLoS Comput Biol. 2013;9(6)
3 US National Cancer Institute, a part of the National Institute of Health (NIH). https://www.cancer.gov/about-cancer/treatment/types/immunotherapy. Accessed April 2024.
4 Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742.
5 Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742.
6 Cleveland Clinic. https://my.clevelandclinic.org/health/body/24630-t-cells. Accessed April 2024.
7 MD Anderson Cancer Center. https://www.mdanderson.org/cancerwise/what-is-the-tumor-microenvironment-3-things-to-know.h00-159460056.html. Accessed April 2024.
8 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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Contact Summit Investor Relations:
Dave Gancarz
Chief Business & Strategy Officer
Nathan LiaBraaten
Senior Director, Investor Relations
Source: Summit Therapeutics Inc.
FAQ
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