Astellas Receives Approval from the European Commission for VYLOY™ (zolbetuximab) in Combination with Chemotherapy for Advanced Gastric and Gastroesophageal Junction Cancer
Astellas Pharma Inc. announced that the European Commission has approved VYLOY™ (zolbetuximab) in combination with chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive. Zolbetuximab is the first and only therapy approved in the European Union to target claudin 18.2, a biomarker positively expressed by 38% of patients with advanced gastric cancer.
Phase 3 clinical trials showed that treatment with zolbetuximab provided statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to standard of care chemotherapies. The European Marketing Authorization is valid in all 27 EU member states, Iceland, Liechtenstein, and Norway. This approval follows recent approvals in the UK and Japan, with further applications submitted to other regulatory agencies worldwide.
Astellas Pharma Inc. ha annunciato che la Commissione Europea ha approvato VYLOY™ (zolbetuximab) in combinazione con la chemioterapia per il trattamento di prima linea di pazienti adulti con adenocarcinoma gastrico o gastroesofageo in fase avanzata, non resecabile o metastatico, HER2-negativo, i cui tumori sono positivi per claudin (CLDN) 18.2. Lo zolbetuximab è la prima e unica terapia approvata nell'Unione Europea per colpire la claudin 18.2, un biomarker positivamente espresso dal 38% dei pazienti affetti da cancro gastrico avanzato.
Gli studi clinici di fase 3 hanno mostrato che il trattamento con zolbetuximab ha fornito miglioramenti statisticamente significativi nella sopravvivenza senza progressione (PFS) e nella sopravvivenza complessiva (OS) rispetto alla chemioterapia standard. L'autorizzazione al commercio in Europa è valida in tutti i 27 stati membri dell'UE, in Islanda, in Liechtenstein e in Norvegia. Questa approvazione segue approvazioni recenti nel Regno Unito e in Giappone, con ulteriori richieste presentate ad altre agenzie regolatorie in tutto il mondo.
Astellas Pharma Inc. anunció que la Comisión Europea ha aprobado VYLOY™ (zolbetuximab) en combinación con quimioterapia para el tratamiento de primera línea en pacientes adultos con adenocarcinoma gástrico o de unión gastroesofágica localmente avanzado, no resecable o metastásico, HER2-negativo, cuyos tumores son positivos para claudin (CLDN) 18.2. El zolbetuximab es la primera y única terapia aprobada en la Unión Europea para dirigirse a claudin 18.2, un biomarcador que se expresa positivamente en el 38% de los pacientes con cáncer gástrico avanzado.
Los ensayos clínicos de fase 3 mostraron que el tratamiento con zolbetuximab proporcionó mejoras estadísticamente significativas en la supervivencia libre de progresión (PFS) y la supervivencia global (OS) en comparación con las quimioterapias estándar. La autorización de comercialización europea es válida en los 27 estados miembros de la UE, Islandia, Liechtenstein y Noruega. Esta aprobación sigue a las recientes aprobaciones en el Reino Unido y en Japón, con más solicitudes presentadas a otras agencias regulatorias en todo el mundo.
Astellas Pharma Inc.는 유럽연합 집행위원회가 VYLOY™ (졸베투지맙)을 HER2 음성의 국소 진행성 절제 불가능 또는 전이성 위암 또는 위식도 접합부 선암의 성인 환자에 대한 1차 치료제로서 화학요법과 병용하여 승인하였다고 발표했습니다. 졸베투지맙은 클라우딘 18.2를 표적으로 하는 유럽연합에서 승인된 첫 번째이자 유일한 치료제입니다, 이는 진행성 위암 환자의 38%에서 양성 발현됩니다.
3상 임상 시험 결과, 졸베투지맙 치료가 표준 화학요법에 비해 무진행 생존기간(PFS)과 전체 생존기간(OS)에서 통계적으로 유의미한 개선을 제공하는 것으로 나타났습니다. 유럽 마케팅 승인은 EU 27개 회원국, 아이슬란드, 리히텐슈타인 및 노르웨이에서 유효합니다. 이번 승인 결정은 영국과 일본에서의 최근 승인에 이어 이루어졌으며, 전 세계의 다른 규제 기관에도 추가 신청이 제출되었습니다.
Astellas Pharma Inc. a annoncé que la Commission européenne a approuvé VYLOY™ (zolbetuximab) en combinaison avec la chimiothérapie pour le traitement de première ligne des patients adultes atteints d'adénocarcinome gastrique ou de jonction gastro-œsophagienne localement avancé, non résécable ou métastatique, HER2-négatif, dont les tumeurs sont positives pour claudin (CLDN) 18.2. Le zolbetuximab est la première et unique thérapie approuvée dans l'Union européenne ciblant la claudin 18.2, un biomarqueur exprimé positivement par 38 % des patients atteints de cancer gastrique avancé.
Les essais cliniques de phase 3 ont montré que le traitement avec le zolbetuximab a fourni des améliorations statistiquement significatives de la survie sans progression (PFS) et de la survie globale (OS) par rapport aux chimiothérapies standards. L'autorisation de mise sur le marché européen est valable dans les 27 États membres de l'UE, en Islande, au Liechtenstein et en Norvège. Cette approbation fait suite à des approbations récentes au Royaume-Uni et au Japon, et d'autres demandes ont été soumises à d'autres agences réglementaires dans le monde entier.
Astellas Pharma Inc. gab bekannt, dass die Europäische Kommission VYLOY™ (Zolbetuximab) in Kombination mit Chemotherapie für die Erstlinienbehandlung erwachsener Patienten mit lokal fortgeschrittenem, nicht resezierbarem oder metastasiertem HER2-negativem Magen- oder gastroösophagealen Übergangsadenokarzinom, deren Tumoren positiv auf Claudin (CLDN) 18.2 sind, genehmigt hat. Zolbetuximab ist die erste und einzige Therapie, die in der Europäischen Union zur gezielten Behandlung von Claudin 18.2, einem Biomarker, der bei 38 % der Patienten mit fortgeschrittenem Magenkrebs positiv exprimiert wird, genehmigt wurde.
Phase-3-Studien zeigten, dass die Behandlung mit Zolbetuximab statistisch signifikante Verbesserungen in der progressionsfreien Überlebenszeit (PFS) und der Gesamtüberlebenszeit (OS) im Vergleich zu den Standard-Chemotherapien bot. Die europäische Marktzulassung gilt in allen 27 EU-Mitgliedstaaten, Island, Liechtenstein und Norwegen. Diese Genehmigung folgt auf kürzliche Genehmigungen im Vereinigten Königreich und in Japan, und es wurden weitere Anträge bei anderen Regulierungsbehörden weltweit eingereicht.
- First and only therapy approved in the EU to target claudin 18.2 in advanced gastric cancer
- Significantly extended progression-free survival and overall survival in Phase 3 trials
- European Marketing Authorization valid in 30 countries
- Aligned with updated ESMO Gastric Cancer Living Guidelines
- Previous approvals in UK and Japan, with ongoing reviews in other countries
- to patients with CLDN18.2 positive tumors (38% of advanced gastric cancer cases)
- Common adverse events include nausea, vomiting, and decreased appetite
- Zolbetuximab is currently the first and only therapy approved in the European Union to target claudin 18.2, a biomarker positively expressed by
- Treatment with the claudin 18.2-targeted monoclonal antibody shown to significantly extend both progression-free survival and overall survival in Phase 3 trials1,2
Zolbetuximab is currently the first and only approved monoclonal antibody specifically designed to target gastric tumor cells that express the biomarker CLDN18.2, offering a more personalized approach to cancer treatment. In the zolbetuximab Phase 3 clinical trials, approximately
Zorana Maravic, Chief Executive Officer of Digestive Cancers Europe (DiCE):
"Sadly, due to similar symptoms to more common stomach conditions, gastric and gastroesophageal junction cancers are often diagnosed at the advanced or metastatic stage when treatment options have traditionally been relatively limited. Ensuring timely diagnosis, followed by personalized treatment and care, will be essential to better survival and quality of life for patients."
Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas:
"We are delighted to bring zolbetuximab, a first-in-class targeted treatment option, to patients in
Data from the Phase 3 SPOTLIGHT and GLOW clinical trials, which supported the European Marketing Authorization, showed that treatment with zolbetuximab provided statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to other standard of care chemotherapies in eligible patients with gastric and GEJ cancers.1,2 In the SPOTLIGHT trial, a median PFS of 10.61 months was achieved with zolbetuximab plus mFOLFOX6 as first-line treatment, versus 8.67 months with placebo plus mFOLFOX6. The median OS was 18.23 months versus 15.54 months in the respective treatment groups.1 Similar efficacy findings were seen in the GLOW trial where median PFS was 8.21 months versus 6.80 months, and median OS 14.39 months versus 12.16 months, with zolbetuximab plus CAPOX, compared to placebo plus CAPOX, respectively.2 In both the SPOTLIGHT and GLOW trials, the incidence of serious treatment emergent adverse events (TEAEs) was similar in the zolbetuximab treatment groups compared to the controls. The most common all-grade TEAEs reported in the zolbetuximab treatment groups were nausea, vomiting and decreased appetite.1,2
The European Marketing Authorization for zolbetuximab is valid in all 27 EU member states as well as
This regulatory approval for zolbetuximab follows the August 2024 approval by the
Astellas has already reflected the impact from this result in its financial forecast for the current fiscal year ending March 31, 2025.
About Zolbetuximab
Zolbetuximab is a claudin 18.2-directed cytolytic antibody investigated in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive. In both the SPOTLIGHT and GLOW Phase 3 clinical trials, approximately
As an investigational first-in-class monoclonal antibody (mAb), zolbetuximab targets and binds to CLDN18.2, a transmembrane protein expressed on cancer cells. In pre-clinical studies, zolbetuximab reduced the number of CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, leading to tumor growth inhibition.3
About Locally Advanced Unresectable Metastatic Gastric and Gastroesophageal Junction Cancer
Gastric and gastroesophageal junction (G/GEJ) cancers are known to be histologically similar, are recommended to be managed in the same way in treatment guidelines, and frequently display aligned responses to treatment.2,8 Across
Because early-stage cancer symptoms frequently overlap with more common stomach-related conditions, G/GEJ cancers are often diagnosed in the advanced or metastatic stage, or once they have spread from the tumor's origin to other body tissues or organs.13
Early signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, bloating of the stomach after meals, and loss of appetite.13,14 Signs of more advanced G/GEJ cancer can include unexplained weight loss, weakness and fatigue, sensation of food getting stuck in the throat while eating, vomiting blood or having blood in the stool.13,14,15 Risk factors associated with G/GEJ cancer can include older age, male gender, family history, H. pylori infection, smoking, and gastroesophageal reflux disease (GERD).16,17
INVESTIGATIONAL STUDIES
About the SPOTLIGHT Phase 3 Clinical Trial
SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab plus mFOLFOX6 (a combination chemotherapy regimen that includes oxaliplatin, leucovorin, and fluorouracil) compared to placebo plus mFOLFOX6 as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive. The study enrolled 565 patients at 215 study locations in the
Data from the SPOTLIGHT clinical trial were presented during the 2023 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium in an oral presentation on January 19, 2023, and were subsequently published in The Lancet on April 14, 2023.1
For more information, please visit clinicaltrials.gov under Identifier NCT03504397.
About the GLOW Phase 3 Clinical Trial
GLOW is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive. The study enrolled 507 patients at 166 study locations in the
Data from the GLOW study were initially presented at the March 2023 ASCO Plenary Series with an updated oral presentation at the 2023 ASCO Annual Meeting on June 3, 2023, and were subsequently published in Nature Medicine on July 31, 2023.2
For more information, please visit clinicaltrials.gov under Identifier NCT03653507.
Investigational Pipeline in CLDN18.2
An expanded Phase 2 trial of zolbetuximab in metastatic pancreatic adenocarcinoma is in progress and recruiting patients. The trial is a randomized, multi-center, open-label study, evaluating the safety and efficacy of investigational zolbetuximab in combination with gemcitabine plus nab-paclitaxel as a first-line treatment in patients with metastatic pancreatic adenocarcinoma with CLDN18.2 positive tumors (defined as ≥
In addition to zolbetuximab, ASP2138 is under development in our Primary Focus Immuno-Oncology area and is currently recruiting patients. ASP2138 is a bispecific monoclonal antibody that binds to CD3 and CLDN18.2, and it is currently in a Phase 1/1b study in participants with metastatic or locally advanced unresectable gastric or GEJ adenocarcinoma or metastatic pancreatic adenocarcinoma whose tumors have CLDN18.2 expression. The safety and efficacy of the agent under investigation have not been established for the uses being considered. For more information, please visit clinicaltrials.gov under Identifier NCT05365581.
There is no guarantee that the agent(s) will receive regulatory approval and become commercially available for the uses being investigated.
About Astellas
Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at https://www.astellas.com/en.
Cautionary Notes
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.
Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.
References |
1 Shitara K, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401(10389):1655-1668. |
2 Shah MA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29(8):2133-2141. |
3 Sahin U, et al. FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Ann Oncol. 2021;32(5):609-19. |
4 European Society for Medical Oncology (ESMO). Gastric Cancer Living Guidelines: Advanced/metastatic unresectable oesophageal, oesophagogastric junction and gastric adenocarcinoma - Metastatic Disease - First-Line Therapy. Available at: https://www.esmo.org/living-guidelines/esmo-gastric-cancer-living-guideline/metastatic-disease/metastatic-disease/first-line/advanced-metastatic-unresectable-oesophageal-oesophagogastric-junction-and-gastric-adenocarcinoma/article/first-line-therapy. Last accessed: September 2024. |
5 GOV.UK. News story: Zolbetuximab Approved to Treat Adults with Stomach or Gastro-oesophageal Junction Cancer. Available at: https://www.gov.uk/government/news/mhra-approves-zolbetuximab. Last accessed: September 2024. |
6 Astellas press release issued 26 March 2024: Astellas' VYLOY™ (zolbetuximab) Approved in |
7 Astellas data on file. |
8 Barra WF, et al. GEJ cancers: gastric or esophageal tumors? Searching for the answer according to molecular identity. Oncotarget. 2017; 8(61):104286–104294. |
9 Ferlay J, et al. World Health Organization. International Agency for Research on Cancer. Global Cancer Observatory. Cancer Factsheet – Stomach. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf. Last accessed: September 2024. |
10 Digestive Cancers Europe. What are Gastric and Oesophageal Cancers? Available at: https://digestivecancers.eu/gastric-esophageal-what/. Last accessed: September 2024. |
11 American Cancer Society. About esophagus cancer (03-20-2020). Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8614.00.pdf. Last accessed: September 2024. |
12 Rawla P and Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Gastroenterology Rev. 2019;14(1):26-38. |
13 American Cancer Society. Stomach Cancer Early Detection, Diagnosis, and Staging (01-22-2021). Available at https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/signs-symptoms.html. Last accessed: September 2024. |
14 National Cancer Institute. Stomach Cancer Symptoms (05-31-2023). Available at: https://www.cancer.gov/types/stomach/symptoms. Last accessed: September 2024. |
15 The Royal Marsden. Stomach cancer symptoms: What are the signs of gastric cancer? (May 2022). Available at: https://www.royalmarsden.nhs.uk/private-care/news-and-blogs/stomach-cancer-symptoms-what-are-signs-gastric-cancer. Last accessed: September 2024. |
16 American Cancer Society. Stomach cancer causes, risk factors and prevention (01-22-2021). Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8839.00.pdf. Last accessed: September 2024. |
17 American Cancer Society. Esophageal cancer causes, risk factors, and prevention (06-09-2020). Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8615.00.pdf. Last accessed: September 2024. |
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FAQ
What is VYLOY (zolbetuximab) approved for in the European Union?
How does zolbetuximab improve survival rates for gastric cancer patients?
What percentage of gastric cancer patients can benefit from zolbetuximab (ALPMY)?
When did Astellas (ALPMY) receive approval for zolbetuximab in other regions?
