A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or lower oesophagus: the MONO study. Median PFS was 102 days. In the phase II study, median OS was 13.2 versus 8.4 months, with IMAB362 and without, respectively (HR, 0.51;P= .0001). For additional information, Read more. Patient-reported outcomes from the phase II FAST trial of zolbetuximab plus EOX compared to EOX alone as first-line treatment of patients with metastatic CLDN18.2+ gastroesophageal adenocarcinoma. Zolbetuximab, a chimeric monoclonal antibody, mediates specific killing of CLDN18.2-positive cells through immune effector mechanisms. For the Astellas criteria on data sharing see: https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx. Ganymed’s lead program, IMAB362, is in advanced Phase II testing for gastroesophageal cancer. Upon malignant transformation, CLDN18.2 epitopes are exposed on the cell surface and accessible to targeted therapy. ...protocol (PP) population of an open-label, European Phase IIa trial showed that 600 mg/m 2 IMAB362.....including 4 partial responses and 6 cases of stable disease. Most adverse events (AEs) related to zolbetuximab + EOX (nausea, vomiting, neutropenia, anaemia) were grade 1-2. 2017 Aug 29;8(8):CD004064. Would you like email updates of new search results? In advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients expressing CLDN18.2, adding zolbetuximab to first-line EOX provided longer PFS and OS versus EOX alone. Zolbetuximab + EOX was generally tolerated and AEs were manageable. Results from a randomized phase II study indicate that adding the experimental antibody IMAB362, which targets the tight junction protein claudin18.2, to standard chemotherapy is more effective than chemotherapy alone in previously untreated patients with advanced gastric cancer. 16. Norman G, Rice S, Spackman E, Stirk L, Danso-Appiah A, Suh D, Palmer S, Eastwood A. Conclusions: IMAB362 antibody therapy of patients with advanced CLDN18.2-positive gastroesophageal adenocarcinomas is safe and well tolerated. 2018 Nov 10;8(1):e1523096. A Phase 2, Open-Label, Randomized Study to Assess the Antitumor Activity and Safety of Zolbetuximab (IMAB362) in Combination with Nab-Paclitaxel and Gemcitabine (Nab-P+GEM) as First Line Treatment in Subjects with Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma IMAB362 binds to the tight junction protein Claudin-18.2 which is expressed in up to 80% of gastroesophageal adenocarcinomas, 60% of pancreatic tumors as well as in other various solid tumors. 8600 Rockville Pike Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: an emerging paradigm. National Library of Medicine The aim of this phase II study is to establish efficacy and safety of multiple doses of IMAB362 as monotherapy in patients suffering from metastatic, refractory or recurrent adenocarcinoma of the stomach or the lower esophagus. doi: 10.1080/2162402X.2018.1523096. In the phase II study, median OS was 13.2 versus 8.4 months, with IMAB362 and without, respectively (HR, 0.51; P = .0001). Conclusions: Each phase has a different goal that helps researchers answer specific questions. A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared with Placebo Plus mFOLFOX6 as First-line Treatment of Subjects with Claudin (CLDN)18.2 Positive, HER2-Negative, Metastatic … Health Technol Assess. The purpose of this study is to confirm the recommended phase 2 dose (RP2D) of zolbetuximab in combination with Nab-P + GEM, determine overall survival and assess the safety and tolerability of the combination treatment. For people ages 16 and 17, a parent or guardian must call their doctor’s office. This study is for patients age 18 and older. Unable to load your collection due to an error, Unable to load your delegates due to an error. Trastuzumab for the treatment of HER2-positive metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Patients with CLDN18.2 expression of ≥2+ in ≥40% tumor cells (as validated by CLAUDE-TECT™ 18.2 Kit), Eastern Cooperative Oncology Group Table 1 Various clinical trials involving claudiximab (IMAB362) IMAB362 nearly doubles survival in patients with the highest levels of Claudin18.2 target MAINZ, Germany, June 5, 2016 /PRNewswire/ -- Ganymed Pharmaceuticals AG, a biopharmaceutical company developing highly targeted immunotherapies against cancer, announced outstanding data from its randomized Phase II clinical study of IMAB362 in first-line treatment of gastric cancer at the ASCO … Ganymed’s lead program, IMAB362, is in advanced Phase 2 testing for gastroesophageal cancer. BM reports honoraria from Angelini Pharma, Astellas, Bayer, BMS, Eliamm, Merck Serono, MSD, Novartis, Pfizer, Roche, and Sanofi. Significant improvement in PFS was also reported in the overall population of arm 3 versus arm 1 (HR = 0.58; 95% CI, 0.39-0.85; P = 0.0114) but not in high CLDN18.2-expressing patients; no significant improvement in OS was observed in either population. The single-arm MONO trial (NCT01197885) assessed IMAB362 (600 mg/m 2) monotherapy as salvage therapy in GA/GEJA patients and showed a 30% disease control rate.The FAST trial (NCT01630083) assessed IMAB362 (loading dose 800 mg/m 2 then 600 mg/m 2) combination therapy as 1st line therapy (IMAB362+EOX followed by single agent IMAB362 maintenance until … advanced gastric cancer; advanced gastroesophageal junction adenocarcinoma; advanced oesophageal adenocarcinoma; capecitabine (EOX); claudin 18.2; epirubicin; oxaliplatin; zolbetuximab. FAST: A randomised phase II study of zolbetuximab (IMAB362) plus EOX vs EOX alone for first-line treatment of advanced CLDN18.2 positive gastric and gastro-oesophageal adenocarcinoma All other authors have declared no conflicts of interest. In Phase 3, the goal is to test the medicine compared to different treatments. Chemotherapy for advanced gastric cancer. Patients must have inoperable or metastatic gastric or GEJ cancer that is positive for the CLDN18.2 protein. The FAST study enrolled advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients (aged ≥18 years) with moderate-to-strong CLDN18.2 expression in ≥40% tumour cells. Clinical trial information: NCT01197885. Patients received: IV IMAB362 Q3W, 800 mg/m 2 on Cycle 1, Day 1 and 600 mg/m 2 on Day 1 of every subsequent cycle; IV ZA 4 mg, Day 1 of Cycles 1 and 3; subcutaneous IL-2, Days 1–3 of Cycles 1 and 3. FL reports personal fees and/or grants from Astellas, AstraZeneca, Bristol-Myers Squibb (BMS), BioNTech, Lilly, Elsevier, Infomedica, Merck, Merck Sharp & Dohme (MSD), Roche, Servier, and Amgen. e15079 Background: IMAB362 is the first-in-class monoclonal antibody against the tight junction molecule claudin 18.2 (CLDN18.2) executing its antitumor activity via 4 highly potent modes of action (antibody-dependent cellular cytotoxicity [ADCC], complement-dependent cytotoxicity, proliferation inhibition, apoptosis). Zolbetuximab (formerly IMAB362) is a chimeric mAb that mediates specific killing of CLDN18.2+ cancer cells through immune effector mechanisms; single-agent activity … This site needs JavaScript to work properly. Additionally, being a co-founder, supervisory board member, and shareholder of BioNTech SE, co-founder, advisor and former supervisory board member of TRON, board member to the cutting-edge technology cluster CI3, and president of the international cancer immunotherapy network CIMT. 2021 Mar 31. doi: 10.1038/s41571-021-00492-2. Online ahead of print. 826 - Claudin 18.2 – a novel treatment target in the multicenter, randomized, phase II FAST study, a trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without the anti-CLDN18.2 antibody IMAB362 as 1st line therapy in advanced gastric and gastroesophageal junction (GEJ) cancer Patients in this study will receive IMAB362 alone or in combination with mFOLFOX6. COVID-19 is an emerging, rapidly evolving situation. IMAB362 targets a protein called CLDN18.2, which is commonly found on tumor cells of stomach and/or GEJ cancers. Results: • Single-dose IMAB362 at doses of 33–1000 mg/m 2 was generally well tolerated. 2019 Sep 1;30(9):1487-1495. doi: 10.1093/annonc/mdz199. Arm 3 (exploratory) was added after enrolment initiation (zolbetuximab + EOX 1000 mg/m2 Q3W, n = 85). Grade ≥3 AEs showed no substantial increases overall (zolbetuximab + EOX versus EOX alone). 2021 Feb 19;S0923-7534(21)00122-8. doi: 10.1016/j.annonc.2021.02.005. Türeci Ӧ, Mitnacht-Kraus R, Wöll S, Yamada T, Sahin U. Oncoimmunology. Background: Physiologically, the tight junction protein CLDN18.2 is present only in the gastric mucosa. Background: The drug is in phase II clinical trials as of January 2013. Nakamura Y, Kawazoe A, Lordick F, Janjigian YY, Shitara K. Nat Rev Clin Oncol. In the context of malignant transformation, CLDN18.2 can be found in gastric tumors as well as tumors from organs that do not normally express CLDN18.2 (eg, pancreas). COVID-19 Vaccine Available to MSK Patients, A Phase II Study of IMAB362 in Patients with Advanced Inoperable Stomach Cancer. OT reports founder and chief executive officer of Ganymed until the end of 2016; currently an employee and chief medical officer of BioNTech; patents for the investigational agent, zolbetuximab, with royalties paid by Astellas; consultancy fees from Astellas Pharma. 2011 May;15 Suppl 1:33-42. doi: 10.3310/hta15suppl1/04. For example, in Phase 2, the goal is to find out if the medicine works and learn more about its safety. This significant PFS benefit was retained in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells (HR = 0.38; 95% CI, 0.23-0.62; P < 0.0005). However, following malignant transformation, gastric cancer metastases maintain this expression. A monoclonal antibody, zolbetuximab (formerly known as IMAB362), has been generated against CLDN18.2. IMAB362 was developed by Ganymed Pharmaceuticals AG. Patients and methods: Patients must be physically well enough that they are fully ambulatory, capable of all self care, and are capable of all but physically strenuous activities. Early evidence for antitumoral activity was observed in the phase II trial. Published by Elsevier Ltd. Disclosure US reports co-founder and shareholder at Ganymed and also holds several patents, with royalties paid by Astellas; founder, chief executive officer, and shareholder of BioNTech. IMAB362 binds to the tight junction protein Claudin-18.2 which is expressed in up to 80% of gastroesophageal adenocarcinomas, 60% of pancreatic tumors as well as in other various solid tumors. Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; upon malignant transformation, CLDN18.2 epitopes become exposed. A Phase 2, Open-Label, Randomized Study to Assess the Antitumor Activity and Safety of Zolbetuximab (IMAB362) in Combination With Nab-Paclitaxel and Gemcitabine (Nab-P + GEM) as First Line Treatment in Subjects With Claudin 18.2 (CLDN18.2) Positive, … Please enable it to take advantage of the complete set of features! IMAB362 extended progression-free and overall survival by 3.1 months and 4.8 months, respectively. A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared With Placebo Plus mFOLFOX6 as First-line Treatment of Subjects With Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin (CLDN) 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma doi: 10.1002/14651858.CD004064.pub4. CH reports being a co-founder, supervisory board member, and shareholder of Ganymed Pharmaceuticals. Background: Claudin 18.2 (CLDN18.2) is physiologically confined to gastric mucosa tight junctions; however, upon malignant transformation, perturbations in cell polarity lead to CLDN18.2 epitopes being exposed on the cancer cell surface. Claudin 18.2 is a tight junction protein that is exclusively expressed in the gastric epithelia. Background. Türeci O, Sahin U, Schulze-Bergkamen H, Zvirbule Z, Lordick F, Koeberle D, Thuss-Patience P, Ettrich T, Arnold D, Bassermann F, Al-Batran SE, Wiechen K, Dhaene K, Maurus D, Gold M, Huber C, Krivoshik A, Arozullah A, Park JW, Schuler M. Ann Oncol. Privacy, Help To be eligible for this study, patients must meet several criteria, including but not limited to the following: For more information about this study and to inquire about eligibility, please contact Dr. David Ilson at 646-888-4183. From radiation therapy to clinical trials to check-ins with your doctor, your care is made as convenient as possible. • IMAB362 (300–600 mg/m 2) was determined as suitable for further evaluation. Zolbetuximab 800/600 mg/m2 is being evaluated in phase III studies based on clinical benefit observed in the overall population and in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells. Therefore, claudin 18.2 is a promising target for immunotherapy. Careers. In the overall population, both PFS [hazard ratio (HR) = 0.44; 95% confidence interval (CI), 0.29-0.67; P < 0.0005] and OS (HR = 0.55; 95% CI, 0.39-0.77; P < 0.0005) were significantly improved with zolbetuximab + EOX (arm 2) compared with EOX alone (arm 1). Researchers think that giving IMAB362 alone or in combination with mFOLFOX6 will help target the chemotherapy to selectively attack cancer cells, and slow or prevent the growth of cancer. References • IMAB362, an anti-CLDN18.2 mAb, mediates tumour cell death through ADCC and CDC. Online ahead of print. Bethesda, MD 20894, Copyright 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. Preliminary results from the phase II 'FAST' trial in June 2016 suggest it is helpful for advanced gastric cancer (and a phase III trial will be planned). A Randomized Phase II Multicenter, Open-Label Study Evaluating the Efficacy and Safety of IMAB362 in Combination With the EOX (Epirubicin, Oxaliplatin, Capecitabine) Regimen as First-Line Treatment of Patients With CLDN18.2-Positive Advanced Adenocarcinomas of the Stomach, the Esophagus or the Gastroesophageal Junction S-EA reports advisory role from Merck, Roche, Celgene, Lilly, Nordic Pharma, BMS, MSD; speaker role from Roche, Celgene, Lilly, Nordic Pharma, AIO gGmbH, MCI, Promedicis, Forum für Medizinische Fortbildung; CEO/founder of IKF Klinische Krebsforschung GmbH; and clinical trial fees from Sanofi, Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly, German Cancer Aid (Krebshilfe), and German Research Foundation; and translational research from the Federal Ministry of Education and Research. A Phase 2 Study of Zolbetuximab (IMAB362) as Monotherapy or in Combination with mFOLFOX6 in Subjects with Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma whose Tumors have High or Intermediate Claudin (CLDN) 18.2 Expression CLDN18.2 is a tumour-specific marker in gastric or gastro-oesophageal junction cancers. The primary endpoint was progression-free survival (PFS) and overall survival (OS) was a secondary endpoint. This study will also evaluate other anti-tumor effects, tumor markers and pharmacokinetics (PK) of zolbetuximab, Nab-P and GEM. AA and JP report employment from Astellas. Copyright © 2021. IMAB362.....A Phase IIb trial is evaluating IMAB362 plus chemotherapy as first-line treatment of gastroesophageal cancer. IMAB362 is a first-in-class monoclonal antibody targeting the cell surface molecule Claudin18.2. IMAB362 is a monoclonal antibody specific for the tight junction protein Claudin 18.2 (CLDN18.2). The median survival of people using the treatment plus … MSK is offering COVID-19 vaccines to our patients 16 and over, who live, work or study in New York State. 2021 Mar 23. doi: 10.1007/s10120-020-01153-6. Data sharing Researchers may request access to anonymised participant level data, trial level data, and protocols from Astellas sponsored clinical trials at www.clinicalstudydatarequest.com. MS reports consultant fees from AstraZeneca, Boehringer Ingelheim, BMS, Novartis, Roche, and Takeda; honoraria from Abbvie, Boehringer Ingelheim, BMS, MSD, Novartis, and Pierre Fabre; research funding from AstraZeneca, Boehringer Ingelheim, BMS, and Novartis, and patents with the University Duisburg-Essen. Patients received first-line epirubicin + oxaliplatin + capecitabine (EOX, arm 1, n = 84) every 3 weeks (Q3W), or zolbetuximab + EOX (loading dose, 800 mg/m2 then 600 mg/m2 Q3W) (arm 2, n = 77). Wagner AD, Syn NL, Moehler M, Grothe W, Yong WP, Tai BC, Ho J, Unverzagt S. Cochrane Database Syst Rev. The purpose of this study is to evaluate the safety and effectiveness of the investigational drug IMAB362 when given alone or in combination with standard mFOLFOX6 chemotherapy (leucovorin calcium, fluorouracil, and oxaliplatin) in patients with inoperable or metastatic stomach cancer or cancer of the gastroesophageal junction (GEJ). Subsequently, a phase IIb (FAST) study evaluated clau-diximab as first line in patients with advanced/recurrent gastric and GEJ cancer. Safety/tolerability, including determination of maximum tolerated dose and recommended phase II dose, were the primary objectives; secondary objectives included assessment of the IMAB362 pharmacokinetic profile, immunogenicity, and antitumour activity (assessed by … Further clinical evaluation of IMAB362 in patients with CLDN18.2 tumors is warranted. Prevention and treatment information (HHS). Accessibility eCollection 2019. KW reports honoraria from Ganymed Pharmaceuticals. The phase 2 clinical trial, involving 161 patients, focused on an antibody called IMAB362. Lordick F, Al-Batran SE, Ganguli A, Morlock R, Sahin U, Türeci Ö. Gastric Cancer. IMAB362 reduced the risk of death or progression by approximately 50% when added to standard chemotherapy for patients with CLDN18.2-positive advanced gastric cancers. In a phase 2 clinical trial (FAST: NCT01630083 ), zolbetuximab in conjunction with chemotherapy prolonged overall and progression-free survival over … © 2021 Memorial Sloan Kettering Cancer Center, Gerstner Sloan Kettering Graduate School of Biomedical Sciences. Characterization of zolbetuximab in pancreatic cancer models. The magnitude of response seen with IMAB362 was proportional to the expression level of CLDN18.2, which is a splice variant of the claudin-18 protein. In normal tissue, CLDN18.2 is exclusively expressed in the gastric mucosa. Keywords: Clipboard, Search History, and several other advanced features are temporarily unavailable. FOIA A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared with Placebo Plus mFOLFOX6 as First-line Treatment of Subjects with Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unr The treatments in this study are given intravenously (by vein). Eligible patients over 18 can use this link to schedule a vaccination. As an example, patients must be well enough that they would be able to carry out office work or light housework. Patients must recover from the serious side effects of prior therapies before entering the study.