HUTCHMED Announces that TAGRISSO® plus ORPATHYS® demonstrated high, clinically meaningful response rate in lung cancer patients with high levels of MET overexpression and/or amplification in SAVANNAH Phase II trial
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) announced positive results from the SAVANNAH Phase II trial, showing that TAGRISSO® (osimertinib) plus ORPATHYS® (savolitinib) demonstrated a high, clinically meaningful, and durable objective response rate (ORR) in patients with EGFR-mutated non-small cell lung cancer (NSCLC) with high levels of MET overexpression and/or amplification. The combination targets MET-driven resistance in EGFR-mutated lung cancer patients who progressed on TAGRISSO® treatment.
Key findings include:
- 62% of screened patients had tumors with MET overexpression and/or amplification
- 34% met the high MET level cut-off upon clinical progression
- The combination received Fast Track designation from the FDA in 2023
- Safety profile was consistent with known profiles of the combination and individual treatments
The global SAFFRON Phase III trial will further assess the combination versus chemotherapy in this patient population.
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) ha annunciato risultati positivi dalla sperimentazione di Fase II SAVANNAH, dimostrando che TAGRISSO® (osimertinib) più ORPATHYS® (savolitinib) ha mostrato un'alta risposta oggettiva (ORR) clinicamente significativa e durevole nei pazienti con cancro ai polmoni non a piccole cellule (NSCLC) mutato per EGFR che presentano alti livelli di sovraespressione e/o amplificazione di MET. Questa combinazione mira a contrastare la resistenza guidata da MET nei pazienti affetti da cancro ai polmoni mutato per EGFR che hanno progressione durante il trattamento con TAGRISSO®.
I risultati chiave includono:
- Il 62% dei pazienti esaminati aveva tumori con sovraespressione e/o amplificazione di MET
- Il 34% ha superato la soglia di alto livello di MET alla progressione clinica
- La combinazione ha ricevuto la designazione di Fast Track dalla FDA nel 2023
- Il profilo di sicurezza è stato coerente con i profili noti della combinazione e dei trattamenti individuali
La sperimentazione globale di Fase III SAFFRON valuterà ulteriormente la combinazione rispetto alla chemioterapia in questa popolazione di pazienti.
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) anunció resultados positivos del ensayo clínico de Fase II SAVANNAH, mostrando que TAGRISSO® (osimertinib) más ORPATHYS® (savolitinib) demostró una alta tasa de respuesta objetiva (ORR) clínicamente significativa y duradera en pacientes con cáncer de pulmón no microcítico (NSCLC) mutado para EGFR que tienen altos niveles de sobreexpresión y/o amplificación de MET. La combinación se dirige a la resistencia impulsada por MET en pacientes con cáncer de pulmón mutado para EGFR que progresaron en el tratamiento con TAGRISSO®.
Los hallazgos clave incluyen:
- El 62% de los pacientes seleccionados tenía tumores con sobreexpresión y/o amplificación de MET
- El 34% cumplió con el umbral de alto nivel de MET al progresar clínicamente
- La combinación recibió la designación de Fast Track por parte de la FDA en 2023
- El perfil de seguridad fue coherente con los perfiles conocidos de la combinación y de los tratamientos individuales
El ensayo global de Fase III SAFFRON evaluará más a fondo la combinación frente a la quimioterapia en esta población de pacientes.
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13)은 SAVANNAH 2상 시험에서 긍정적인 결과를 발표하였으며, TAGRISSO®(오시머티닙)와 ORPATHYS®(사볼리티닙)의 조합이 EGFR 변이 비소세포 폐암(NSCLC) 환자에서 MET의 고수준 발현 및/또는 증폭이 있는 경우 높은 임상적 의미가 있는 지속적인 객관적 반응률(ORR)을 보였음을 보여주었습니다. 이 조합은 TAGRISSO® 치료 후 진행된 EGFR 변이 폐암 환자에서 MET에 의해 유도된 내성에 대응합니다.
주요 발견은 다음과 같습니다:
- 선별된 환자의 62%가 MET의 고발현 및/또는 증폭이 있는 종양을 가지고 있었습니다.
- 34%는 임상 진행 시 MET의 높은 수준 컷오프를 충족했습니다.
- 이 조합은 2023년 FDA로부터 신속 심사(Fast Track) 지정을 받았습니다.
- 안전성 프로필은 조합과 각 개별 치료제의 알려진 프로필과 일치했습니다.
글로벌 SAFFRON 3상 시험은 이 환자 집단에서 조합을 화학요법과 비교하여 추가 평가할 것입니다.
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) a annoncé des résultats positifs de l'essai de phase II SAVANNAH, montrant que TAGRISSO® (osimertinib) plus ORPATHYS® (savolitinib) a montré un taux de réponse objectif (ORR) élevé, cliniquement significatif et durable chez les patients atteints de cancer du poumon non à petites cellules (NSCLC) muté pour EGFR avec des niveaux élevés de surexpression et/ou d'amplification de MET. La combinaison vise à cibler la résistance induite par MET chez les patients atteints de cancer du poumon muté pour EGFR ayant progressé sous traitement avec TAGRISSO®.
Les principales conclusions sont les suivantes :
- 62 % des patients sélectionnés avaient des tumeurs avec surexpression et/ou amplification de MET
- 34 % ont atteint le seuil de haut niveau de MET lors de la progression clinique
- La combinaison a reçu la désignation Fast Track de la FDA en 2023
- Le profil de sécurité était cohérent avec les profils connus de la combinaison et des traitements individuels
L'essai mondial SAFFRON de phase III évaluera davantage la combinaison par rapport à la chimiothérapie dans cette population de patients.
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) gab positive Ergebnisse aus der SAVANNAH-Phase-II-Studie bekannt, die zeigen, dass TAGRISSO® (Osimertinib) plus ORPATHYS® (Savolitinib) eine hohe, klinisch bedeutsame und dauerhafte objektive Ansprechrate (ORR) bei Patienten mit EGFR-mutiertem nicht-kleinzelligem Lungenkrebs (NSCLC) mit hohen MET-Überexpressionen und/oder Amplifikationen zeigte. Die Kombination zielt auf die MET-gesteuerte Resistenz bei EGFR-mutierten Lungenkrebspatienten ab, die während der Behandlung mit TAGRISSO® fortgeschritten sind.
Wichtige Ergebnisse umfassen:
- 62 % der gesichteten Patienten hatten Tumoren mit MET-Überexpression und/oder Amplifikation
- 34 % erfüllten die hohe MET-Level-Grenze bei klinischer Progression
- Die Kombination erhielt 2023 die Fast-Track-Bezeichnung von der FDA
- Das Sicherheitsprofil war konsistent mit den bekannten Profilen der Kombination und der einzelnen Behandlungen
Die globale SAFFRON-Phase-III-Studie wird die Kombination weiter im Vergleich zur Chemotherapie in dieser Patientengruppe bewerten.
- High and clinically meaningful objective response rate (ORR) in EGFR-mutated NSCLC patients with high MET levels
- Fast Track designation from FDA for TAGRISSO® plus ORPATHYS® combination
- Potential new treatment option for patients who developed resistance to TAGRISSO®
- 62% of screened patients had MET overexpression and/or amplification
- Consistent safety profile with no new safety signals identified
- None.
Insights
This data from the SAVANNAH Phase II trial is highly significant for patients with EGFR-mutated non-small cell lung cancer (NSCLC) who develop resistance to TAGRISSO® (osimertinib). The combination of TAGRISSO® and ORPATHYS® (savolitinib) showed a high and clinically meaningful objective response rate in patients with high levels of MET overexpression and/or amplification.
Key points:
- MET is a common resistance biomarker, found in
62% of screened patients 34% met the high MET level cut-off upon clinical progression- The combination strategy addresses MET-driven resistance while continuing TAGRISSO® treatment
- Safety profile was consistent with known profiles of both drugs
This targeted approach could potentially become the first biomarker-driven combination therapy in this setting, addressing a significant unmet need. The ongoing SAFFRON Phase III trial will further evaluate this combination against chemotherapy, which could lead to a new standard of care for these patients.
This positive clinical data has significant implications for HUTCHMED (HCM) and its partner AstraZeneca:
- Market Expansion: Potential to address a large subset of NSCLC patients who develop resistance to first-line EGFR inhibitors
- Competitive Advantage: First-mover potential in biomarker-driven combination therapy for this indication
- Revenue Growth: If approved, could drive substantial sales for ORPATHYS®, benefiting both HUTCHMED and AstraZeneca
- Regulatory Fast-Track: FDA Fast Track designation could accelerate approval process
- Global Opportunity: Data will be shared with global regulatory authorities, indicating potential for worldwide commercialization
For HUTCHMED, with a market cap of
— New data demonstrate efficacy for the oral treatment combination to address MET-driven resistance in EGFR-mutated lung cancer —
— MET is a common biomarker in this setting for patients who develop resistance to EGFR targeted therapies —
HONG KONG and SHANGHAI and FLORHAM PARK, N.J., Oct. 16, 2024 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces positive high-level results from the SAVANNAH Phase II trial that showed TAGRISSO® (osimertinib) plus ORPATHYS® (savolitinib) demonstrated a high, clinically meaningful and durable objective response rate (“ORR”) for patients with epidermal growth factor receptor-mutated (“EGFRm”) non-small cell lung cancer (“NSCLC”) with high levels of MET overexpression and/or amplification, defined as IHC90+ and/or FISH10+, whose disease progressed on treatment with TAGRISSO®. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. In 2023, TAGRISSO® plus ORPATHYS® received Fast Track designation from the US Food and Drug Administration (FDA) in this setting.
ORPATHYS® is an oral, potent, and highly selective MET tyrosine kinase inhibitor (“TKI”) being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca. It is approved in China for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy.
While EGFR-targeted therapy can provide a substantial survival benefit to patients with EGFRm NSCLC, most will eventually develop resistance to their treatment, with MET being a common resistance biomarker.1 Among patients screened for enrollment in SAVANNAH, an estimated
Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and principal investigator in the SAVANNAH Phase II trial, said: “Osimertinib can provide patients with EGFR-mutated lung cancer unprecedented survival and has transformed the treatment landscape, but patients can develop resistance due to genes like MET – a common resistance biomarker. These results show that adding savolitinib, a selective MET-inhibitor, while continuing osimertinib treatment helped to deliver a meaningful response among patients whose disease progressed, providing a potential new treatment option following standard-of-care osimertinib.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “These positive SAVANNAH results show the benefit of a targeted treatment approach in EGFR-mutated lung cancer patients who experience MET-driven resistance. The improved response rates from ORPATHYS® added to TAGRISSO®, which is the backbone EGFR-mutated lung cancer therapy, reinforce the importance of identifying MET aberration and validate our combination strategy to address resistance while allowing continued TAGRISSO® treatment.”
Weiguo Su, Chief Executive Officer and Chief Scientific Officer, HUTCHMED, said: “Previous results from the SAVANNAH Phase II trial provided a novel biomarker approach for identifying patients with MET overexpression and/or amplification who are most likely to benefit from a MET-directed therapy, an existing unmet need. These new, positive results affirm our selective, patient-centric approach, which could allow us to deliver the first biomarker-driven targeted therapy combination option in this setting.”
The safety and tolerability of TAGRISSO® plus ORPATHYS® was consistent with the known safety profiles of the combination and each treatment alone. No new safety signals were identified.
On August 2022, initial positive ORR results from the SAVANNAH trial were presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (WCLC).
The global SAFFRON Phase III trial sponsored by AstraZeneca will further assess the TAGRISSO® plus ORPATHYS® combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following TAGRISSO®. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH.
About NSCLC and MET aberrations
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.2,3 Lung cancer is broadly split into NSCLC and small cell lung cancer.4 Each year there are an estimated 2.4 million people diagnosed with lung cancer globally, with 80
MET is a tyrosine kinase receptor that has an essential role in normal cell development. MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is the primary mechanism of acquired resistance to EGFR TKIs for metastatic EGFRm NSCLC. Among patients who experience disease progression post-osimertinib treatment, approximately 15
About SAVANNAH
SAVANNAH is an ongoing global, randomised, Phase II trial sponsored by AstraZeneca studying the efficacy of ORPATHYS® added to TAGRISSO® in patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification who progressed following treatment with TAGRISSO®. Based on the original single-arm trial design, patients were treated with ORPATHYS® 300 or 600 mg once-daily (QD) or 300 mg twice-daily, in combination with oral TAGRISSO® 80 mg QD. In 2022, a registrational component was added to the trial that compared ORPATHYS® 300 mg twice-daily and TAGRISSO® 80 mg QD to ORPATHYS® 300 mg twice-daily and placebo.
The trial enrolled over 360 patients in more than 80 centers globally, including in North America, Europe, South America and Asia. The primary endpoint is ORR and key secondary endpoints include progression-free survival and duration of response.
About TAGRISSO®
TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. TAGRISSO® (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO® as a treatment for patients across multiple stages of EGFRm NSCLC.
There is an extensive body of evidence supporting the use of TAGRISSO® as standard of care in EGFRm NSCLC. TAGRISSO® improved patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial.
About ORPATHYS®
ORPATHYS® (savolitinib) is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.
It is approved in China for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is the first selective MET inhibitor approved in China and the first in the National Reimbursement Drug List of China (NRDL).
It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines. In addition to SAVANNAH and SAFFRON, in China the combination of savolitinib and osimertinib in lung cancer is also being studied in the SACHI and SANOVO Phase III trials.
About HUTCHMED
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit www.hutch-med.com or follow us on LinkedIn.
Forward-Looking Statements
This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of savolitinib, the further clinical development for savolitinib, its expectations as to whether any studies on savolitinib would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study’s inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of savolitinib, including as a combination therapy, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential market of savolitinib for a targeted indication; and the sufficiency of funding; and AstraZeneca’s ability to successfully develop and commercialize savolitinib.. In addition, as certain studies rely on the use of other drug products such as osimertinib as combination therapeutics with savolitinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the US Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise.
Medical Information
This announcement contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.
Inside Information
This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).
CONTACTS
| Investor Enquiries | +852 2121 8200 / ir@hutch-med.com |
| Media Enquiries | |
| Ben Atwell / Alex Shaw, FTI Consulting | +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.com |
| Zhou Yi, Brunswick | +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com |
| Nominated Advisor | |
| Atholl Tweedie / Freddy Crossley / Rupert Dearden, Panmure Liberum | +44 (20) 7886 2500 |
1 Del Re M, et al. Understanding the Mechanisms of Resistance in EGFR-Positive NSCLC: From Tissue to Liquid Biopsy to Guide Treatment Strategy. Int J Mol Sci. 2019;20(16): 3951.
2 World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed September 2024.
3 World Health Organization. International Agency for Research on Cancer. World Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf. Accessed October 2024.
4 LUNGevity Foundation. Types of Lung Cancer. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed September 2024.
5 Cheema PK, et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol. 2019;26(1):37-42.
6 Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27.
7 Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in 11. Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12.
8 Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013;66:79-89.
9 Soria JC, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125.
10 Mok TS, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017;376(7):629-640.
11 Hartmaier R, et al. Tumor genomics in patients (pts) with advanced epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC) whose disease has progressed on first-line (1L) osimertinib therapy in the Phase II ORCHARD study. Cancer Res 15 June 2022; 82 (12_Supplement): LB078.
12 Piotrowska, et al. MET amplification (amp) as a resistance mechanism to osimertinib. Journal of Clinical Oncology 2017 35:15_suppl, 9020-9020.
13 Hartmaier, et al. Detection of MET-mediated EGFR tyrosine kinase inhibitor (TKI) resistance in advanced non-small cell lung cancer (NSCLC): biomarker analysis of the TATTON study. Cancer Res (2019) 79 (13_Supplement): 4897.
14 Coleman N, et al. Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in oncogene-driven non-small-cell lung cancer. ESMO Open. 2019;6(6).
FAQ
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