Efficacy and Safety of Multiple Doses of Imab362 in Patients with Advanced Gastro-Esophageal Cancer: Results of a Phase Ii Study

Trarbach, Tanja; Schüler, Martin; Zvirbule, Zanete; Lordick, Florian; Крилова, А.С.; Helbig, Ulrike; Schulze‐Bergkamen, Henning; Thuss‐Patience, Peter; Wichert, Goetz von; Schmiegel, Wolff; Bauer, S.; Muller, Carolyn; Al-Batran, S-E.; Huber, Christoph; Maurus, Daniel; Kühnle, Marie-Cristine; Şahin, Uğur; Türeci, Özlem

doi:10.1093/annonc/mdu334.21

Cited by 15 publications

(10 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: 50%

“…Serious side effects were not observed. The most frequently observed side effects, including nausea and vomiting, should be easily treatable by already well-known potent anti-emetics (18)(19)(20)30). These results provide an outlook for an effective and low-side effect therapy in patients with advanced or metastatic EAC, which should be investigated in future clinical trials.…”

Section: Discussionmentioning

confidence: 85%

“…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%

“…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: 50%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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Dawn of precision medicine on gastric cancer

2019

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Prognostic impact of Claudin 18.2 in gastric and esophageal adenocarcinomas

et al. 2020

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Introduction The tight junction molecule Claudin 18.2 is selectively expressed in healthy and malignant gastric epithelial tissue and is a promising therapy target for high Claudin 18.2 expressing adenocarcinomas of the esophagogastric junction and stomach (AEG/S). Methods This study analyzed the prevalence, characteristics and prognostic impact of Claudin 18.2 expression in primary tumor, lymph node and distant metastasis in a large Caucasian AGE/S cohort with 414 patients. Results Claudin 18.2 was highly expressed in 17.1% of primary tumors, 26.7% of lymph node metastasis and 16.7% of distant metastasis. High Claudin 18.2 expression in lymph node metastasis and primary tumors correlated significantly (p < 0.001). High expression of Claudin 18.2 was neither associated with histomorphogical subtype, or tumor state, nor with overall survival. Conclusion In Caucasian AEG/S patients, 17.1% appeared to be eligible for an anti-Claudin 18.2 therapy. Claudin 18.2 expression itself has no impact on prognosis and is not related to any tumor subtype.

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Efficacy and Safety of Multiple Doses of Imab362 in Patients with Advanced Gastro-Esophageal Cancer: Results of a Phase Ii Study

Cited by 15 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

Dawn of precision medicine on gastric cancer

Prognostic impact of Claudin 18.2 in gastric and esophageal adenocarcinomas

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