FAST: An international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without IMAB362, a first-in-class anti-CLDN18.2 antibody, as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma.

Al-Batran, Salah-Eddin; Schüler, Martin; Zvirbule, Zanete; Manikhas, G.; Lordick, Florian; Rusyn, A.; Vynnyk, Yuriy; Vynnychenko, Ihor; Fadeeva, Natalia; Nechaeva, M.; Dudov, A.; Gotovkin, Evgeny; Pecheniy, Alexander; Bazin, I.; Бондаренко, И. Н.; Melichar, B; Mueller, Christian; Huber, Christoph; Tureci, Oezlem; Şahin, Uğur

doi:10.1200/jco.2016.34.15_suppl.lba4001

Cited by 29 publications

(32 citation statements)

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“…To best of our knowledge, the present study is the largest systematic investigation of claudin 18.2 protein expression in EAC (n=485) in addition to the first study to detect claudin 18.2 expression in corresponding regional lymph node metastases using a commercially available monoclonal antibody, which was also used in other studies on gastric cancer (18)(19)(20)30). The present study demonstrated detectable claudin 18.2 expression in up to 18.4% of EAC cases.…”

Section: Discussionmentioning

confidence: 49%

“…Claudin 18.2 is an interesting tight-junction protein that may be therapeutically modifiable and whose relevance is currently being tested in studies on gastric cancer (16,(18)(19)(20)(21)28). In these studies, the response to therapy is associated with the measurable presence of the protein in the tumor (16,(18)(19)(20)(21)30). This may make claudin 18.2 a relevant biomarker, as we have known for years with programmed death-ligand 1, HER2/neu or hormone receptors in breast carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding claudin 18.2 as a potential target for immunotherapy, the present results have an impact on potential future therapeutic strategies. IMAB362, a novel antibody targeting claudin 18.2, has been investigated in various phase I and phase II studies for patients with gastric and/or gastro-esophageal junction cancer and has exhibited anti-tumor activity (16,(18)(19)(20)(21)28). Gastrointestinal toxicities were the most commonly observed treatment-associated adverse events (18)(19)(20)30).…”

Section: Discussionmentioning

confidence: 99%

“…no DS9800) was used for 5 min at 37˚C. The primary antibody detects the same isoform 2 of Claudin 18 as described in clinical studies previously (19,30). Normal gastric mucosa served as an internal control.…”

Section: Methodsmentioning

confidence: 99%

“…IMAB362 is currently undergoing a number of phase I and IIb trials, which have revealed that IMAB362 is well-tolerated, exhibits anti-tumor activity and improves the disease control rate and progression-free survival time when administered as a monotherapy or in combination with chemotherapy. The most frequently observed treatment-associated adverse events include nausea and vomiting (18)(19)(20)(21).…”

Section: Claudin 182 Expression In Esophageal Adenocarcinoma and Itsmentioning

confidence: 99%

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Claudin 18.2 expression in esophageal adenocarcinoma and its potential impact on future treatment strategies

et al. 2020

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The incidence of esophageal adenocarcinoma (EAC) has rapidly increased, particularly in the Western world. Despite improvements in perioperative treatments, the overall survival of patients remains low. Claudin 18.2 is a tight junction protein that is exclusively expressed in the gastric epithelia. However, following malignant transformation, gastric cancer metastases maintain this expression. Therefore, claudin 18.2 is a promising target for immunotherapy. Previous clinical trials have revealed improved anti-tumor activity in patients treated with an anti-claudin antibody by investigating the expression of claudin 18.2 in tumor cells. However, there is currently very limited data on the importance of claudin 18.2 expression in EAC. The present study analyzed the distribution of claudin 18.2 using immunohistochemistry in 485 patients with EAC, including their lymph node metastases. Additionally, these results were associated with clinical and molecular data. Claudin 18.2 was detected in 89/485 patients (18.4%). No correlations between expression and clinicopathological data (sex, age, pT stage, lymph node metastasis and grading) were observed. However, significantly decreased claudin 18.2 expression was observed in tumor types with upregulated human epidermal growth factor receptor 2 expression (P=0.036). Additionally, neoadjuvant treatment did not have any significant impact on claudin 18.2 expression (P= 0.331). To the best of our knowledge, the present study is the largest systematic investigation of claudin 18.2 protein expression in EAC. The results obtained suggested that claudin 18.2 may serve as a promising therapeutic target in a substantial number of patients with EAC.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Claudin 182 Expression In Esophageal Adenocarcinoma and Itsmentioning

confidence: 99%

See 3 more Smart Citations

Claudin 18.2 expression in esophageal adenocarcinoma and its potential impact on future treatment strategies

et al. 2020

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Medical management of gastric cancer: a 2017 update

et al. 2017

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Gastric cancer remains a considerable health burden throughout the world. The Cancer Genome Atlas (TCGA) analysis has recently unveiled 4 genotypes of gastric cancer with data not ready to change treatment strategy yet. A multimodality approach to therapy is the cornerstone of screening, diagnosing, staging, treating and supporting patients with gastric cancer. The evidence‐based approach to localized gastric cancer (>cT1b) is to use an either preoperative or postoperative strategy to maximize the benefit of surgery. The focus of future research is to optimize chemotherapy regimens, determine the role of radiation therapy and investigate the effect of treatment timing. In metastatic gastric cancer, biologic therapies have been introduced targeting markers shown to be prognostic. The results of ongoing randomized controlled phase 3 trials using targeted and immunotherapy agents, either in combination or alone, have the potential to alter the current treatment landscape of advanced gastric cancer.

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Optimal management of gastroesophageal junction cancer

Greally

Agarwal

Ilson

2019

Cancer

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Although recent decades have witnessed incremental improvements in the treatment of gastroesophageal junction (GEJ) carcinoma, outcomes remain modest. For locally advanced esophageal cancer, the addition of chemotherapy and/or radiation to surgery is considered the standard of care. Chemotherapy remains the primary treatment for metastatic disease and improves survival over best supportive care. However, the prognosis for patients with GEJ cancers, which are treated along the same paradigms as esophageal and gastric carcinomas, remain poor because of the emergence of chemoresistance and limited targeted therapeutic approaches, which include agents that target the HER2 and vascular endothelial growth factor pathways. Evaluation of immune checkpoint inhibitors in the chemorefractory setting have confirmed the activity of immunotherapy in esophagogastric cancer. Ongoing immunotherapeutic strategies are being evaluated in both the locally advanced and metastatic settings. This review focuses on the treatment of locally advanced and metastatic GEJ carcinomas, which encompass all tumors that have an epicenter within 5 cm proximal or distal to the anatomical Z‐line (Siewert classification). Because the vast majority of GEJ tumors are adenocarcinoma, the management of adenocarcinoma is the focus of this review. Evolving approaches and areas of clinical equipoise are discussed.

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FAST: An international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without IMAB362, a first-in-class anti-CLDN18.2 antibody, as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma.

Cited by 29 publications

References 0 publications

Claudin 18.2 expression in esophageal adenocarcinoma and its potential impact on future treatment strategies

Claudin 18.2 expression in esophageal adenocarcinoma and its potential impact on future treatment strategies

Medical management of gastric cancer: a 2017 update

Optimal management of gastroesophageal junction cancer

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