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Poster display session

2068 - Phase 1 Study of IMAB362 with Immunomodulation in Patients with Advanced Gastric Cancer

Date

09 Sep 2017

Session

Poster display session

Topics

Clinical Research;  Immunotherapy;  Gastric Cancer

Presenters

Salah-Eddin Al-Batran

Citation

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

Authors

S. Al-Batran1, Z. Zvirbule2, F. Lordick3, P. Thuss-Patience4, M. Just5, M. Bitzer6, V. Brass7, A. Krilova8, D. Maurus9, Ö. Türeci9, U. Sahin10

Author affiliations

  • 1 Institute Of Clinical Cancer Trials (icct), Krankenhaus Nordwest, 60488 - Frankfurt am Main/DE
  • 2 Latvian Oncology Center, Riga East University, 1079 - Riga/LV
  • 3 University Cancer Center Leipzig, University Hospital Leipzig, 04103 - Leipzig/DE
  • 4 Medical Clinic Of Hematology, Oncology And Tumor Immunology, Charite University Medicine Berlin, 13353 - Berlin/DE
  • 5 Oncology, Practice for Oncology Bielefeld, Bielefeld/DE
  • 6 Department Of Internal Medicine I Gastroenterology, Hepatology, Infectious Diseases, University Hospital Tuebingen, 72076 - Tübingen/DE
  • 7 Clinic Of Internal Medicine Ii, Gastroenterology And Hepatology, University Hospital Freiburg, Freiburg/DE
  • 8 Oncology Clinic, Piejuras Hospital, 3401 - Liepaja/LV
  • 9 Ganymed Pharmaceuticals, AG, Mainz/DE
  • 10 Translational Oncology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz/DE
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Resources

Abstract 2068

Background

IMAB362, a monoclonal antibody to Claudin 18.2 (CLDN18.2), has demonstrated strong tumor cell killing activity via antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in preclinical gastric cancer models. Safety/tolerability, pharmacodynamics (PD), and clinical response of IMAB362 in combination with zoledronic acid (ZA) and interleukin-2 (IL-2), which expand and activate ADCC-mediating gamma9delta2 T cell effector populations, was assessed in patients with advanced upper GI adenocarcinomas.

Methods

This open-label phase 1 exploratory study (NCT01671774) enrolled heavily pretreated patients (age ≥18 yrs) whose tumor cells had CLDN18.2 staining intensity either 2+ in ≥ 40% cells or any 3+ by IHC. Patients were enrolled into 1 of 4 treatment arms: Arm 1, IMAB362 + ZA; Arm 2, IMAB362 + ZA + 1 million IU (mIU) IL-2; Arm 3, IMAB362 + ZA + 3 mIU IL-2; Arm 4, IMAB362 alone. Patients received: IV IMAB362 Q3W, 800 mg/m2 on Cycle 1, Day 1 and 600 mg/m2 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. Safety/tolerability of IMAB362, immune cell phenotyping by flow cytometry and IMAB362-induced ADCC in a cytotoxicity assay were primary endpoints; clinical response (per RECIST v1.1) was a secondary endpoint.

Results

Of the 29 enrolled patients, 28 received treatment (Arm 1, n = 7; Arm 2, n = 9; Arm 3, n = 7; Arm 4, n = 5), 21 were in the PD analyses, and 19 in response analyses. IMAB362 had acceptable safety/tolerability unaltered by immunomodulation; grade 1–4 nausea and vomiting (both n = 15/28; 54%) were the most common adverse events. Expansion and activation of gamma9delta2 T cells and activation of NK cells were initiated by all treatment arms; however, these effects were more extensive in pts treated with IMAB362 + ZA/IL-2 (n = 10 [5 each in Arms 2 and 3]). A strong ADCC in response to IMAB362 was observed in most patients; however, ADCC kinetics over time and dependency on ZA/IL-2 were not conclusive. No patient achieved confirmed response; 11 (58%) had confirmed stable disease.

Conclusions

This study provided encouraging data on safety/tolerability and cytotoxicity of IMAB362 in combination with ZA/IL-2. Objective responses were not observed.

Clinical trial identification

NCT01671774, August 21, 2012

Legal entity responsible for the study

Ganymed Pharmaceuticals, A company of Astellas Pharma, Inc

Funding

Ganymed Pharmaceuticals, A company of Astellas Pharma, Inc

Disclosure

F. Lordick: Personal fees: Ganymed Pharmaceuticals AG during the study, Amgen, Biontech, Lilly, Nordic, Roche, Taiho, BMS, MSD outside the study, non- financial support: Boston Biomedical, MSD, Roche, grants: Fresenius Biotech, BMS. P. Thuss-Patience: Grants, non-financial support: Roche, personal fees: MSD, Roche, BMS, Nordic. M. Bitzer: Personal fees: Bayer Healthcare. D. Maurus: Employee of Ganymed Pharamceuticals AG, a company of Astellas Pharma, Inc. 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. U. Sahin: Stock option owner, ex-shareholder and cofounder of Ganymed Pharmaceuticals AG and Founder/CEO/shareholder of Biontech Holding outside the submitted work, several patents issued to this work that have been acquired by Astellas. All other authors have declared no conflicts of interest.

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