Arm 3 (exploratory) was added after enrolment initiation (zolbetuximab + EOX 1000 mg/m2 Q3W, n = 85). 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. 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. 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. doi: 10.1080/2162402X.2018.1523096. BM reports honoraria from Angelini Pharma, Astellas, Bayer, BMS, Eliamm, Merck Serono, MSD, Novartis, Pfizer, Roche, and Sanofi. For additional information, Read more. 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. 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 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. Zolbetuximab, a chimeric monoclonal antibody, mediates specific killing of CLDN18.2-positive cells through immune effector mechanisms. Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; upon malignant transformation, CLDN18.2 epitopes become exposed. 2021 Mar 23. doi: 10.1007/s10120-020-01153-6. Subsequently, a phase IIb (FAST) study evaluated clau-diximab as first line in patients with advanced/recurrent gastric and GEJ cancer. 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. KW reports honoraria from Ganymed Pharmaceuticals. 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 … For people ages 16 and 17, a parent or guardian must call their doctor’s office. Prevention and treatment information (HHS). The primary endpoint was progression-free survival (PFS) and overall survival (OS) was a secondary endpoint. Chemotherapy for advanced gastric cancer. 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 … In normal tissue, CLDN18.2 is exclusively expressed in the gastric mucosa. 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. AA and JP report employment from Astellas. In Phase 3, the goal is to test the medicine compared to different treatments. CLDN18.2 is a tumour-specific marker in gastric or gastro-oesophageal junction cancers. • IMAB362, an anti-CLDN18.2 mAb, mediates tumour cell death through ADCC and CDC. For example, in Phase 2, the goal is to find out if the medicine works and learn more about its safety. Patients and methods: In the phase II study, median OS was 13.2 versus 8.4 months, with IMAB362 and without, respectively (HR, 0.51; P = .0001). 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 Patients must have inoperable or metastatic gastric or GEJ cancer that is positive for the CLDN18.2 protein. 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. From radiation therapy to clinical trials to check-ins with your doctor, your care is made as convenient as possible. Zolbetuximab (formerly IMAB362) is a chimeric mAb that mediates specific killing of CLDN18.2+ cancer cells through immune effector mechanisms; single-agent activity … IMAB362.....A Phase IIb trial is evaluating IMAB362 plus chemotherapy as first-line treatment of gastroesophageal cancer. 2021 Mar 31. doi: 10.1038/s41571-021-00492-2. In a phase 2 clinical trial (FAST: NCT01630083 ), zolbetuximab in conjunction with chemotherapy prolonged overall and progression-free survival over … 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 Each phase has a different goal that helps researchers answer specific questions. © 2021 Memorial Sloan Kettering Cancer Center, Gerstner Sloan Kettering Graduate School of Biomedical Sciences. This study will also evaluate other anti-tumor effects, tumor markers and pharmacokinetics (PK) of zolbetuximab, Nab-P and GEM. 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 eCollection 2019. Online ahead of print. 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. Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: an emerging paradigm. As an example, patients must be well enough that they would be able to carry out office work or light housework. Türeci Ӧ, Mitnacht-Kraus R, Wöll S, Yamada T, Sahin U. Oncoimmunology. For the Astellas criteria on data sharing see: https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx. 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 IMAB362 is a first-in-class monoclonal antibody targeting the cell surface molecule Claudin18.2. 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. IMAB362 targets a protein called CLDN18.2, which is commonly found on tumor cells of stomach and/or GEJ cancers. In the phase II study, median OS was 13.2 versus 8.4 months, with IMAB362 and without, respectively (HR, 0.51;P= .0001). Privacy, Help 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. 2011 May;15 Suppl 1:33-42. doi: 10.3310/hta15suppl1/04. All other authors have declared no conflicts of interest. Careers. Upon malignant transformation, CLDN18.2 epitopes are exposed on the cell surface and accessible to targeted therapy. Would you like email updates of new search results? 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. Please enable it to take advantage of the complete set of features! CH reports being a co-founder, supervisory board member, and shareholder of Ganymed Pharmaceuticals. Patients in this study will receive IMAB362 alone or in combination with mFOLFOX6. Clinical trial information: NCT01197885. 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. • Single-dose IMAB362 at doses of 33–1000 mg/m 2 was generally well tolerated. Grade ≥3 AEs showed no substantial increases overall (zolbetuximab + EOX versus EOX alone). Bethesda, MD 20894, Copyright Median PFS was 102 days. Accessibility 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. • IMAB362 (300–600 mg/m 2) was determined as suitable for further evaluation. 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 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. Copyright © 2021. A monoclonal antibody, zolbetuximab (formerly known as IMAB362), has been generated against CLDN18.2. The treatments in this study are given intravenously (by vein). 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). Eligible patients over 18 can use this link to schedule a vaccination. 2018 Nov 10;8(1):e1523096. 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). This study is for patients age 18 and older. The phase 2 clinical trial, involving 161 patients, focused on an antibody called IMAB362. COVID-19 Vaccine Available to MSK Patients, A Phase II Study of IMAB362 in Patients with Advanced Inoperable Stomach Cancer. Ganymed’s lead program, IMAB362, is in advanced Phase 2 testing for gastroesophageal cancer. IMAB362 is a monoclonal antibody specific for the tight junction protein Claudin 18.2 (CLDN18.2). FOIA COVID-19 is an emerging, rapidly evolving situation. Results: Lordick F, Al-Batran SE, Ganguli A, Morlock R, Sahin U, Türeci Ö. Gastric Cancer. Most adverse events (AEs) related to zolbetuximab + EOX (nausea, vomiting, neutropenia, anaemia) were grade 1-2. 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. Clipboard, Search History, and several other advanced features are temporarily unavailable. Norman G, Rice S, Spackman E, Stirk L, Danso-Appiah A, Suh D, Palmer S, Eastwood A. Nakamura Y, Kawazoe A, Lordick F, Janjigian YY, Shitara K. Nat Rev Clin Oncol. 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: 10.1002/14651858.CD004064.pub4. 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). 2019 Sep 1;30(9):1487-1495. doi: 10.1093/annonc/mdz199. 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, … Characterization of zolbetuximab in pancreatic cancer models. Ganymed’s lead program, IMAB362, is in advanced Phase II testing for gastroesophageal cancer. Claudin 18.2 is a tight junction protein that is exclusively expressed in the gastric epithelia. Background: References Keywords: 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. 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. The drug is in phase II clinical trials as of January 2013. However, following malignant transformation, gastric cancer metastases maintain this expression. IMAB362 extended progression-free and overall survival by 3.1 months and 4.8 months, respectively. 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. This site needs JavaScript to work properly. 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. Further clinical evaluation of IMAB362 in patients with CLDN18.2 tumors is warranted. 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). 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. 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. 8600 Rockville Pike 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) 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. Trastuzumab for the treatment of HER2-positive metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. The median survival of people using the treatment plus … Background. MSK is offering COVID-19 vaccines to our patients 16 and over, who live, work or study in New York State. 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 … 2021 Feb 19;S0923-7534(21)00122-8. doi: 10.1016/j.annonc.2021.02.005. IMAB362 was developed by Ganymed Pharmaceuticals AG. Conclusions: IMAB362 antibody therapy of patients with advanced CLDN18.2-positive gastroesophageal adenocarcinomas is safe and well tolerated. 2017 Aug 29;8(8):CD004064. 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 ...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. Conclusions: 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 … 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). Unable to load your collection due to an error, Unable to load your delegates due to an error. Therefore, claudin 18.2 is a promising target for immunotherapy. 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). National Library of Medicine advanced gastric cancer; advanced gastroesophageal junction adenocarcinoma; advanced oesophageal adenocarcinoma; capecitabine (EOX); claudin 18.2; epirubicin; oxaliplatin; zolbetuximab.