A Phase 1/1b Study of ASP2138 in Participants With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma or Metastatic Pancreatic Adenocarcinoma Whose Tumors Have Claudin (CLDN) 18.2 Expression

Claudin 18.2 protein, or CLDN18.2 is a protein found on cells in the digestive system. It is also found on some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to 2 targets at the same time: CLDN18.2 and a protein called CD3 found on immune cells, called T-cells. ASP2138 works by binding to both the tumor cell and CD3 which "tells" the immune system to attack the tumor.
ASP2138 is a potential new treatment for people with stomach cancer, gastroesophageal junction cancer, (cancer where the tube that carries food (esophagus) joins the stomach) or pancreatic cancer. Before ASP2138 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. This information will help to find a suitable dose and to check for potential medical problems from the treatment.
Adults 18 years or older with stomach cancer, gastroesophageal junction cancer, or pancreatic cancer can take part. Their cancer is locally advanced unresectable or metastatic. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body.
The main aims of the study are to check the safety of ASP2138, how well it is tolerated, and to find a suitable dose of ASP2138 to be used later in this study.
This is an open-label study. This means that people who take part in this study and clinic staff will know that people will receive ASP2138.
The study will have 2 phases. In phase 1, different small groups of people will receive lower to higher doses of ASP2138. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP2138 to use later in the study. The first group will receive the lowest dose of ASP2138. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP2138. The panel will do this for each group until all groups have received ASP2138, or until suitable doses have been selected for later in the study. Doctors will also check how each type of cancer is responding to ASP2138.
In phase 1b, other different small groups will receive suitable doses of ASP2138 found from phase 1. Phase 1b will check how each type of cancer responds to ASP2138. The response to ASP2138 is measured using scans and blood tests. Doctors will continue to check for all medical problems throughout the study.
ASP2138 will be given either through a vein in the arm (intravenous infusion) or just below the skin (subcutaneous injection). Treatment will be in cycles of either 7 or 14 days (1 or 2 weeks). In each treatment cycle, intravenous infusions or subcutaneous injections will either be given once a week or once every 2 weeks.
People will continue to receive treatment until: their cancer gets worse; they have medical problems they can't tolerate; they ask to stop treatment; the doctors decide that continuing treatment is no longer in that person's best interest; the study is ended by the sponsor. Doctors will check if people had any medical problems from ASP2138. Other checks will include medical examinations, checking the nervous system, blood and urine tests and vital signs. Nervous system checks include checking peoples state of mind, reflexes, balance, movement and muscle strength. Vital signs include medical examinations, body temperature, breathing rate, and blood oxygen levels. Electrocardiograms (ECG) will be done to check the heart rhythm during the study. People will receive ASP2138 in a hospital. They will have blood tests and doctors will check for medical problems. People will also visit the clinic on certain days during their treatment, with extra visits during the first 3 cycles of treatment.
People will visit the clinic after treatment has finished. The doctors will check for more medical problems. Other checks will include medical examinations, blood and urine tests, and vital signs. People will also have an ECG and may have CT or MRI scans.
After this, people will visit the clinic for a check-up several times. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not.

开始日期2022-06-07

申办/合作机构

Astellas Pharma Global Development, Inc.

100 项与 ASP2138 相关的临床结果

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100 项与 ASP2138 相关的转化医学

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100 项与 ASP2138 相关的专利（医药）

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项与 ASP2138 相关的新闻（医药）

2024-03-26

·PRNewswire

Astellas' VYLOY™ (zolbetuximab) Approved in Japan for Treatment of Gastric Cancer

VYLOY approved in combination with chemotherapy for patients with human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2 positive, unresectable, advanced or recurrent gastric cancer MHLW approval makes VYLOY the first and only CLDN18.2-targeted therapy approved in the world TOKYO, March 26, 2024 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") today announced that on March 26, 2024, Japan's Ministry of Health, Labour and Welfare (MHLW) approved VYLOY™ (zolbetuximab), an anti-claudin 18.2 (CLDN18.2) monoclonal antibody for patients with CLDN18.2 positive, unresectable, advanced or recurrent gastric cancer. VYLOY is the first and only CLDN18.2-targeted therapy approved by any regulatory agency in the world. Gastric cancer is frequently diagnosed in the advanced or metastatic stage due to overlapping early-stage symptoms with other more common stomach conditions.1 Despite efforts to reduce its impact, gastric cancer is the third deadliest cancer in Japan, with 126,724 cases diagnosed in 2022.2 Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas "The approval of VYLOY by the MHLW marks a new era in the treatment of gastric cancer, offering the first and only targeted therapy option for CLDN18.2-positive patients living with this devastating disease. Astellas is proud to help address the urgent therapeutic need for this hard-to-treat cancer in Japan, where incidence rates are among the highest globally. Importantly, this approval holds the potential to provide eligible patients with more precious time with their loved ones, delivering on our commitment to improve patient outcomes." Kohei Shitara, MD, Primary Investigator for the SPOTLIGHT Trial and Head, Department of Gastrointestinal Oncology, the National Cancer Center Hospital East in Kashiwa, Japan "Developing new targeted therapies is critical for diseases like advanced gastric adenocarcinoma, which has had very limited treatment options and is often discovered at an advanced stage. As the primary investigator for the Phase 3 SPOTLIGHT clinical trial, I witnessed firsthand the significant improvement in progression-free survival and overall survival for patients treated with VYLOY in combination with chemotherapy compared to those treated with placebo plus chemotherapy. These results support VYLOY as a new treatment option for the CLDN18.2-positive population in Japan, where there were nearly 44,000 deaths caused by gastric cancer in 2022 alone." The approval is based on results from the Phase 3 SPOTLIGHT and GLOW clinical trials for first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors were CLDN18.2 positive.3,4 The SPOTLIGHT study evaluated VYLOY plus mFOLFOX6 (a combination chemotherapy regimen that includes oxaliplatin, leucovorin, and fluorouracil) compared to placebo plus mFOLFOX6.4 The GLOW study evaluated VYLOY plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX.3 Both trials met their primary endpoint, progression-free survival (PFS), as well as a key secondary endpoint, overall survival (OS), showing statistical significance in patients treated with VYLOY plus chemotherapy compared to placebo plus chemotherapy. The most frequent treatment-emergent adverse events (TEAEs) ≥20% for VYLOY in combination with mFOLFOX6 or CAPOX were nausea, vomiting, decreased appetite, neutropenia, and decreased weight. In clinical trials, adverse reactions were managed by antiemetics, dose interruptions, and infusion rate adjustments.3,4 In both SPOTLIGHT and GLOW, approximately 38% of patients screened had tumors that were CLDN18.2 positive.3,4 CLDN18.2 positivity is defined as ≥75% of tumor cells showing moderate-to-strong membranous CLDN18 staining, which should be confirmed by a pathologist or laboratory with adequate experience using the approved in-vitro diagnostic agent or medical device.3,4 Astellas collaborated with Roche Diagnostics on the newly approved VENTANA® CLDN18 (43-14A) RxDx Assay, an immunohistochemistry (IHC) companion diagnostic (CDx) test, to identify patients who may be eligible for VYLOY.5 Testing will be available in Japan at multiple central laboratories and is expected to expand to additional laboratories over time. Astellas has also submitted applications for VYLOY to regulatory agencies around the world, and review is ongoing. Astellas has already reflected the impact from this approval in its financial forecast for the current fiscal year ending March 31, 2024. About VYLOY™ VYLOY™ (zolbetuximab) is an anti-claudin 18.2 (CLDN18.2) monoclonal antibody that is approved by Japan's Ministry of Health, Labour and Welfare (MHLW) for patients with CLDN18.2 positive, unresectable, advanced or recurrent gastric cancer. VYLOY is used in combination with chemotherapy for patients whose tumors are human epidermal growth factor receptor 2 (HER2)-negative. VYLOY is the first and only CLDN18.2-targeted therapy approved by any regulatory agency in the world. CLDN18.2 positivity should be confirmed by a pathologist or laboratory with adequate experience using the approved in-vitro diagnostic agent or medical device. As an antibody directed against human CLDN18.2, VYLOY binds to CLDN18.2 expressed on cell membrane in cancer cells such as gastric cancer and shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), leading to tumor growth inhibition.3,4 Important Safety Information For Important Safety Information for VYLOY, please see the Package Insert. About Unresectable, Advanced or Recurrent Gastric Cancer Gastric cancer, also known as stomach cancer, is the fifth most commonly diagnosed cancer worldwide.6 Gastric cancer killed 43,807 people in Japan in 2022, making it the third deadliest cancer by number of deaths in the country.2 Signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, diarrhea or constipation, bloating of the stomach after meals, loss of appetite, and sensation of food getting stuck in the throat while eating.1 Signs of more advanced gastric cancer can include unexplained weight loss, weakness and fatigue, and vomiting blood or having blood in the stool.7 Risk factors associated with gastric cancer can include older age, male gender, family history, H. pylori infection, and smoking.8 Because early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions, gastric cancer is often diagnosed in the advanced or metastatic stage, or once it has spread from the tumor's origin to other body tissues or organs.1 The five-year relative survival rate for patients at the metastatic stage is 6.6%.9 INVESTIGATIONAL STUDIES About 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 gastroesophageal junction (GEJ) adenocarcinoma whose tumors were CLDN18.2 positive. The study enrolled 565 patients at 215 study locations in the U.S., Canada, United Kingdom, Australia, Europe, South America, and Asia, including Japan. The primary endpoint is progression-free survival (PFS) of participants treated with the combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), safety and tolerability, and quality-of-life parameters. 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, 2023.4 For more information, please visit clinicaltrials.gov under Identifier NCT03504397. About 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 U.S., Canada, United Kingdom, Europe, South America, and Asia, including Japan. The primary endpoint is PFS in participants treated with the combination of zolbetuximab plus CAPOX compared to those treated with placebo plus CAPOX. Secondary endpoints include OS, ORR, DOR, safety and tolerability, and quality-of-life parameters. 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, 2023.3 For more information, please visit clinicaltrials.gov under Identifier NCT03653507. Investigational Pipeline in Targeting CLDN18.2 An expanded Phase 2 trial of zolbetuximab in metastatic pancreatic adenocarcinoma is in progress. 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 ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining based on a validated immunohistochemistry assay). For more information, please visit clinicaltrials.gov under Identifier NCT03816163. In addition to zolbetuximab, ASP2138 is under development in our Primary Focus Immuno-Oncology. 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 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 . 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 American Cancer Society. Signs and symptoms of stomach cancer (01-22-2021). Available at . Accessed 01-09-2024. 2 Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2024). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available at . Accessed 02-06-2024. 3 Shah, M.A., Shitara, K., Ajani, J.A. et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med (2023). . 4 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. The Lancet. Published online April 14, 2023; S0140-6736(23)00620-7. 5 DATA ON FILE. 6 Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. 7 National Cancer Institute. Gastric cancer treatment (PDQ®): patient version (08-24-2021). Available at . Accessed 01-18-2024. 8 American Cancer Society. Stomach cancer risk factors (01-22-2021). Available at . Accessed 01-09-2024. 9 National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: stomach cancer. Available at . Accessed 01-16-2024. SOURCE Astellas Pharma Inc.

临床结果上市批准临床3期ASCO会议临床2期

2023-07-31

·PRNewswire

China's National Medical Products Administration Accepts Astellas' Biologics License Application for Zolbetuximab

TOKYO, July 31, 2023 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") today announced that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted the Biologics License Application (BLA) for zolbetuximab, a first-in-class investigational Claudin 18.2 (CLDN18.2)-targeted monoclonal antibody, for first-line treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2-positive. If approved, zolbetuximab would be the first CLDN18.2-targeted therapy available in China for these patients. Moitreyee Chatterjee-Kishore, PhD, MBA, Senior Vice President and Head of Immuno-Oncology Development, Astellas "China accounts for nearly half of the world's new cases of gastric cancer, with more than 478,000 new cases diagnosed and more than 373,000 deaths in 2020. The CDE's acceptance of our BLA for zolbetuximab brings us one step closer to having a new therapy available for Chinese patients with advanced-stage disease and in need of treatment options." The BLA is based on results from the Phase 3 GLOW and SPOTLIGHT clinical trials. The GLOW study evaluated zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX. In the GLOW study, 145 patients were randomized in mainland China. The SPOTLIGHT study evaluated zolbetuximab plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6. In the SPOTLIGHT study, 36 patients were randomized in mainland China. In both GLOW and SPOTLIGHT, approximately 38% of patients screened for the trials had tumors that were CLDN18.2-positive (≥75% of tumor cells with moderate-to-strong membranous CLDN18 staining intensity), as determined by a validated immunohistochemistry assay.1,2 Astellas has already reflected the impact from this acceptance in its financial forecast of the current fiscal year ending March 31, 2024. About Locally Advanced Unresectable or Metastatic Gastric and Gastroesophageal Junction Cancer Gastric cancer, also commonly known as stomach cancer, is the fifth most commonly diagnosed cancer worldwide.3 In China, gastric cancer ranks third among incidences of all cancer, with more than 478,000 cases diagnosed and more than 373,000 deaths in 2020.4 Signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, diarrhea or constipation, bloating of the stomach after meals, loss of appetite, and sensation of food getting stuck in the throat while eating.5 Signs of more advanced gastric cancer can include unexplained weight loss, weakness and fatigue and vomiting blood or having blood in the stool.6 Risk factors associated with gastric cancer can include older age, male gender, family history, H. pylori infection, smoking and gastroesophageal reflux disease (GERD).5,7 Because early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions, gastric cancer is often diagnosed in the advanced or metastatic stage, or once it has spread from the tumor's origin to other body tissues or organs.5 The five-year relative survival rate for patients at the metastatic stage is 6.6%.8 Gastroesophageal junction (GEJ) adenocarcinoma is a cancer that starts at the area where the esophagus joins the stomach.9 About Zolbetuximab Zolbetuximab is an investigational, first-in-class chimeric IgG1 monoclonal antibody (mAb) that targets and binds to Claudin 18.2 (CLDN18.2), a transmembrane protein. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways — antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).10 Zolbetuximab has not been approved by any regulatory bodies for the treatment of patients with gastric and GEJ cancers, and there is no guarantee the agent will receive regulatory approval or become commercially available for the uses being investigated. INVESTIGATIONAL STUDIES About GLOW Phase 3 Clinical Trial GLOW is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) 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 U.S., Canada, United Kingdom, Europe, South America and Asia, including China. The primary endpoint is progression-free survival (PFS) in participants treated with the combination of zolbetuximab plus CAPOX compared to those treated with placebo plus CAPOX. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), safety and tolerability and quality-of-life parameters. Data from the GLOW study were initially presented at the March 2023 American Society of Clinical Oncology (ASCO) Plenary Series with an updated oral presentation at the 2023 ASCO Annual Meeting on June 3.1 For more information, please visit clinicaltrials.gov under Identifier NCT03653507. About SPOTLIGHT Phase 3 Clinical Trial SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus mFOLFOX6 (a combination 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 U.S., Canada, United Kingdom, Australia, Europe, South America and Asia, including China. The primary endpoint is PFS in participants treated with the combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6. Secondary endpoints include OS, ORR, DOR, safety and tolerability and quality-of-life parameters. 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 and were subsequently published in The Lancet on April 14.2 For more information, please visit clinicaltrials.gov under Identifier NCT03504397. Investigational Pipeline in CLDN18.2 An expanded Phase 2 trial in metastatic pancreatic adenocarcinoma is in progress. 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 ≥75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining based on a validated immunohistochemistry assay). For more information, please visit clinicaltrials.gov under Identifier NCT03816163. In addition to zolbetuximab, ASP2138 is under development in our Primary Focus Immuno-Oncology. ASP2138 is a bispecific monoclonal antibody that binds to CD3 and CLDN18.2, and it is currently in a Phase 1 trial for people with gastric, GEJ or pancreatic adenocarcinoma. 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 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 . 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 Xu RH, Shitara K, Ajani JA, et al. Updates on Abstract 405736: Zolbetuximab + CAPOX in 1L claudin-18.2+ (CLDN18.2+)/HER2− locally advanced (LA) or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary phase 3 results from GLOW. Presented at: 2023 ASCO Annual Meeting. Abstract 405736. 2 Shitara K, et al. Zolbetuximab plus mFOLFOX6 in patients with claudin-18 isoform 2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastrooesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. The Lancet. Published online April 14, 2023; S0140-6736(23)00620-7. 3 Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. 4 World Health Organization. Cancer Today. Available at: . Last accessed July 18, 2023. 5 American Cancer Society. Signs and symptoms of stomach cancer (01-22-2021). Available at . Last accessed July 18, 2023. 6 National Cancer Institute. Gastric cancer treatment (PDQ®): patient version (08-24-2021). Available at . Last accessed July 18, 2023. 7 American Cancer Society. Esophageal cancer risk factors (06-09-2020). Available at . Last accessed July 18, 2023. 8 National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: stomach cancer. Available at . Last accessed July 18, 2023. 9 American Cancer Society. About esophagus cancer (03-20-2020). Available at . Last accessed July 18, 2023. 10 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. SOURCE Astellas Pharma Inc.

临床2期临床3期临床结果ASCO会议临床1期

2023-07-13

·PRNewswire

European Medicines Agency Accepts Astellas' Marketing Authorization Application for Zolbetuximab

TOKYO, July 13, 2023 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") today announced the European Medicines Agency (EMA) has accepted for regulatory review the company's marketing authorization application (MAA) for zolbetuximab, a first-in-class investigational Claudin 18.2 (CLDN18.2)-targeted monoclonal antibody, for first-line treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2-positive. If approved, zolbetuximab would be the first CLDN18.2-targeted therapy available in Europe for these patients. Gastric cancer accounted for 3.1% of all new cancer cases in Europe in 2020, with around 136,000 new cases diagnosed.1 The average five-year survival rate for patients with gastric cancer in Europe is 26% across all stages.2 "Patients with gastric cancer in Europe face extremely low five-year survival rates regardless of their disease stage, and innovative therapies that extend survival are needed," said Moitreyee Chatterjee-Kishore, PhD, MBA, Senior Vice President and Head of Immuno-Oncology Development, Astellas. "The EMA's acceptance of the zolbetuximab MAA continues a cascade of regulatory milestones for Astellas that are aimed at bringing a new option to patients with advanced gastric and GEJ cancer." The MAA is based on results from the Phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study evaluated zolbetuximab plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6. The GLOW study evaluated zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX. In both SPOTLIGHT and GLOW, approximately 38% of patients screened for the trials had tumors that were CLDN18.2-positive (≥75% of tumor cells with moderate-to-strong membranous CLDN18 staining intensity), as determined by a validated immunohistochemistry assay.3,4 The anticipated recommendation by the Committee for Medicinal Products for Human Use (CHMP) of the EMA regarding the MAA and subsequent European Commission (EC) decision are expected in calendar year 2024. Astellas has already reflected the impact from this acceptance in its financial forecast of the current fiscal year ending March 31, 2024. About Locally Advanced Unresectable or Metastatic Gastric and Gastroesophageal Junction Cancer Gastric cancer, also commonly known as stomach cancer, is the fifth most commonly diagnosed cancer worldwide.5 Gastric cancer accounted for 3.1% of all new cancer cases in Europe in 2020, with around 136,000 new cases diagnosed.1 The average five-year survival rate for patients with gastric cancer in Europe is 26% across all stages.2 Signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, diarrhea or constipation, bloating of the stomach after meals, loss of appetite, and sensation of food getting stuck in the throat while eating.6 Signs of more advanced gastric cancer can include unexplained weight loss, weakness and fatigue and vomiting blood or having blood in the stool.7 Risk factors associated with gastric cancer can include older age, male gender, family history, H. pylori infection, smoking and gastroesophageal reflux disease (GERD).6,8 Because early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions, gastric cancer is often diagnosed in the advanced or metastatic stage, or once it has spread from the tumor's origin to other body tissues or organs.6 The five-year relative survival rate for patients at the metastatic stage is 6.6%.9 Gastroesophageal junction (GEJ) adenocarcinoma is a cancer that starts at the area where the esophagus joins the stomach.10 About Zolbetuximab Zolbetuximab is an investigational, first-in-class chimeric IgG1 monoclonal antibody (mAb) that targets and binds to Claudin 18.2 (CLDN18.2), a transmembrane protein. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways — antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).11 Zolbetuximab has not been approved by any regulatory bodies for the treatment of patients with gastric and GEJ cancers, and there is no guarantee the agent will receive regulatory approval or become commercially available for the uses being investigated. INVESTIGATIONAL STUDIES About SPOTLIGHT Phase 3 Clinical Trial SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus mFOLFOX6 (a combination 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 U.S., Canada, United Kingdom, Australia, Europe, South America and Asia. The primary endpoint is progression-free survival (PFS) in participants treated with the combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), safety and tolerability and quality-of-life parameters. 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 and were subsequently published in The Lancet on April 14.3 For more information, please visit clinicaltrials.gov under Identifier NCT03504397. About GLOW Phase 3 Clinical Trial GLOW is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) 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 U.S., Canada, United Kingdom, Europe, South America and Asia. The primary endpoint is PFS in participants treated with the combination of zolbetuximab plus CAPOX compared to those treated with placebo plus CAPOX. Secondary endpoints include OS, ORR, DOR, safety and tolerability and quality-of-life parameters. Data from the GLOW study were initially presented at the March 2023 American Society of Clinical Oncology (ASCO) Plenary Series with an updated oral presentation at the 2023 ASCO Annual Meeting on June 3.4 For more information, please visit clinicaltrials.gov under Identifier NCT03653507. Investigational Pipeline in CLDN18.2 An expanded Phase 2 trial in metastatic pancreatic adenocarcinoma is in progress. 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 ≥75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining based on a validated immunohistochemistry assay). For more information, please visit clinicaltrials.gov under Identifier NCT03816163. In addition to zolbetuximab, ASP2138 is under development in our Primary Focus Immuno-Oncology. ASP2138 is a bispecific monoclonal antibody that binds to CD3 and CLDN18.2, and it is currently in a Phase 1 trial for people with gastric, GEJ or pancreatic adenocarcinoma. 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 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 . 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 World Health Organization. Cancer Today. Available at: . Last accessed June 28, 2023. 2 Rawla P and Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Przeglad gastroenterologiczny 2019;14(1):26-38. 3 Shitara K, et al. Zolbetuximab plus mFOLFOX6 in patients with claudin-18 isoform 2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastrooesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomized, double-blind, phase 3 trial. The Lancet. Published online April 14, 2023; S0140-6736(23)00620-7. 4 Xu RH, Shitara K, Ajani JA, et al. Updates on Abstract 405736: Zolbetuximab + CAPOX in 1L claudin-18.2+ (CLDN18.2+)/HER2− locally advanced (LA) or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary phase 3 results from GLOW. Presented at: 2023 ASCO Annual Meeting. Abstract 405736. 5 Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. 6 American Cancer Society. Signs and symptoms of stomach cancer (01-22-2021). Available at . Last accessed June 28, 2023. 7 National Cancer Institute. Gastric cancer treatment (PDQ®): patient version (08-24-2021). Available at . Last accessed June 28, 2023. 8 American Cancer Society. Esophageal cancer risk factors (06-09-2020). Available at . Last accessed June 28, 2023. 9 National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: stomach cancer. Available at . Last accessed June 28, 2023. 10 American Cancer Society. About esophagus cancer (03-20-2020). Available at . Last accessed June 28, 2023. 11 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. SOURCE Astellas Pharma Inc.

临床结果ASCO会议临床3期上市批准临床1期

100 项与 ASP2138 相关的药物交易

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研发状态

适应症	最高研发状态	国家/地区	公司
胃癌	临床1期	日本更多	Astellas Pharma Global Development, Inc. 更多
胰腺癌	临床1期	美国更多	Astellas Pharma Global Development, Inc. 更多
胃食管交界处癌	临床1期	-	Astellas Pharma, Inc. 更多
胰腺腺泡癌	临床1期	-	Astellas Pharma, Inc. 更多
CLDN18.2阳性胃食管交界处腺癌	临床申请批准	中国更多	Astellas Pharma Global Development, Inc. 更多