Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session

1963 - First-in-Human Study of IMAB362, an Anti-Claudin 18.2 Monoclonal Antibody, in Patients with Advanced Gastroesophageal Cancer

Date

09 Sep 2017

Session

Poster display session

Topics

Clinical Research;  Oesophageal Cancer;  Gastric Cancer

Presenters

Ugur Sahin

Citation

Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369

Authors

U. Sahin1, M. Schuler2, S. Bauer3, A. Krilova4, M. Utsch5, C. Huber6, Ö. Türeci5

Author affiliations

  • 1 Translational Oncology, University Medical Center of the Johannes Gutenberg University Mainz, 55122 - Mainz/DE
  • 2 Department Of Medical Oncology, West German Cancer Center, University Hospital Essen, 45122 - Essen/DE
  • 3 Onkologisches Zentrum Lebach, Gemeinschaftspraxis Hematology and Oncology, 66822 - Lebach/DE
  • 4 Oncology Clinic, Liepaja Piejuras Hospital, 3401 - Liepaja/LV
  • 5 Ganymed Pharmaceuticals, AG, Mainz/DE
  • 6 Translational Oncology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz/DE
More

Resources

Abstract 1963

Background

Claudin 18.2 (CLDN18.2), a gastric mucosa tight junction protein, is aberrantly expressed in various cancers. IMAB362, an anti-CLDN18.2 monoclonal antibody, specifically binds to CLDN18.2-positive cancer cells. This first-in-human (FIH), dose-escalation study evaluated the clinical effects of IMAB362 in patients with advanced gastroesophageal cancer (GEC) after a single IV infusion.

Methods

This phase 1 study (NCT00909025), conducted at 6 centers in Germany and Latvia, enrolled patients (≥18 yrs) with advanced GEC into 5 sequential dose-escalations cohorts (33, 100, 300, 600, 1000 mg/m2) that followed a 3 + 3 design. Safety/tolerability, including determination of maximum tolerated dose (MTD) based on emergence of dose-limiting toxicities (DLTs), was the primary objective; secondary objectives included assessment of the IMAB362 pharmacokinetic (PK) profile, immunogenicity, and antitumor activity (assessed by RECIST v1.0).

Results

All 15 enrolled patients (median age 61.3 years [range: 46–76]) had received ≥1 prior chemotherapy with nearly half (n = 7/15; 47%) having undergone previous radiotherapy. All IMAB362 doses tested were generally well tolerated; as no DLT was observed within 4 weeks of treatment the MTD was not established. Mild-to-moderate gastrointestinal disorders (eg, nausea, vomiting) were the most common treatment-related adverse events (AEs); however, no clear dose dependency was observed. Neither of the 2 serious AEs (grade 2 odynophagia [300 mg/m2]; grade 3 urinary retention [600 mg/m2]) was considered treatment related. No antibodies against IMAB362 were detected. Most patients (n = 12/15; 80%) showed progressive disease at Weeks 4–5 after a single IMAB362 IV infusion; however, 1 patient in the 600 mg/m2 dose group had stable disease for ∼2 months postinfusion. The linear, dose-proportional PK profile supports IMAB362 dosing at 300–600 mg/m2 every 2 weeks.

Conclusions

Single-dose administration of IMAB362 was well tolerated up to 1000 mg/m2 in this FIH dose-escalation study. These results encourage further clinical testing of IMAB362 in patients with CLDN18.2-positive GEC.

Clinical trial identification

NCT00909025, May 18, 2009

Legal entity responsible for the study

Ganymed Pharmaceuticals AG, A company of Astellas Pharma, Inc.

Funding

Ganymed Pharmaceuticals AG, A company of Astellas Pharma, Inc.

Disclosure

U. Sahin: Stock option owner, ex-shareholder and cofounder of Ganymed Pharmaceuticals AG, founder, CEO, shareholder of Biontech Holding, several patents issued to this work that have been acquired by Astellas. M. Schuler: Work at University Hospital Essen, University Duisburg-Essen and Rurlandklinik. Grant from Novartis, personal fees from AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, Novartis, Roche, Alexion, MSD. M. Utsch: Employee of Ganymed Pharmaceuticals AG, a company of Astellas Pharma, Inc, patent PCT/EP2012/002210 issued. C. Huber: Grants from Fed. Min. of Ed. & Res GER, during conduct of study, personal fees from Ganymed Pharmaceuticals AG & Biontech, grants from and board member of cluster individualized imt-ci3, and president Assoc. CIMT. Ö. Türeci: Stock option owner, ex-shareholder, cofounder & CEO of Ganymed Pharmaceuticals AG, consultancy fees from Astellas, several patents issued to this work that have been acquired by Astellas. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.