Zolbetuximab Claudin18.2 Positive, HER2 Negative, Advanced Gastric Cancer

NCT06767449 | Recruiting

• 1 other identifier: 4-2024-1274
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

• Treatment effectiveness in the real world
• Adverse effects
• Tissue samples collected (multiplex IHC to assess PD-L1 expression, MMR gene status, and Claudin18.2)
• Blood samples collected (ctDNA, scRNAseq, or immune cell profiling)

Conditions

Advanced Gastric Cancer

Keywords

Zolbetuximab

Outcome Measures

Primary Outcomes (3)

• Treatment effectiveness

  Progression-free survival, overall survival, response rate

  2 year

• Number of participants with treatment-related adverse events as assessed by CTCAE V5.0

  Adverse effects will be evaluated according to the NCI CTCAE v5.0

  2 year

• molecular marker Analysis

  * Tissue samples collected before treatment, during treatment, and at disease progression will be analyzed using multiplex IHC to assess PD-L1 expression, MMR gene status, and Claudin18.2. Additionally, NGS testing will be conducted to evaluate the correlation with the treatment response to zolbetuximab. * Blood samples will be collected before treatment, during treatment, and after treatment completion to analyze ctDNA, scRNAseq, or immune cell profiling.

  2 year

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Treatment effectiveness in the real world (progression-free survival, overall survival, response rate, etc.) * Adverse effects will be evaluated according to the NCI CTCAE v5.0 * Tissue samples collected before treatment, during treatment, and at disease progression will be analyzed using multiplex IHC to assess PD-L1 expression, MMR gene status, and Claudin18.2. Additionally, NGS testing will be conducted to evaluate the correlation with the treatment response to zolbetuximab. * Blood samples will be collected before treatment, during treatment, and after treatment completion to analyze ctDNA, scRNAseq, or immune cell profiling.

You may qualify if:

• Patient is ≥ 19 years of age at the time of consent.
• The patient must have histologically confirmed locally advanced, unresectable, or metastatic gastric or gastroesophageal junction adenocarcinoma
• Patient whose tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining as determined by local or central IHC testing.
• The tumor sample must be HER2-negative (IHC 0, 1+, or IHC 2+/ISH-).
• The patient must have received Zolbetuximab as a first-line treatment.
• Patient has ECOG performance status 0 or 1.
• Patient must meet all of the following criteria based on the locally analyzed laboratory tests collected.
• Hb ≥8 g/dL (For patients who require a transfusion, it is appropriate if Hb ≥9 g/dL after transfusion)
• ANC ≥1.0 x 10\^9/L
• Platelet ≥75 x 10\^9/L
• Total bilirubin ≤1.5 x ULN without liver metastasis, or \<3.0 x ULN if liver metastasis is present
• AST or ALT ≤2.5 x ULN without liver metastasis, or ≤5 x ULN if liver metastasis is present
• Estimated creatinine clearance ≥30 mL/min

You may not qualify if:

• Patient has previously received treatment in a clinical trial of zolbetuximab, or a clinical trial that included zolbetuximab as 1 of the treatment options, even if the patient was not given zolbetuximab
• History of known or suspected hypersensitivity to Zolbetuximab, other monoclonal antibodies, or components of the used formulations.
• Patient has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, patient may have received either neo-adjuvant or adjuvant chemotherapy, immunotherapy or other systemic anticancer therapies as long as it was completed at least 6 months prior to participation.
• Patients who have received systemic immunosuppressive therapy, including systemic corticosteroids, within 14 days before enrollment. However, patients using physiological replacement doses of hydrocortisone or its equivalent (maximum hydrocortisone 30 mg/day or prednisone 10 mg/day), those who have received a single dose of systemic corticosteroid, or those who have received systemic corticosteroids as premedication for radiologic contrast agents are allowed.
• Patient has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting
• Per investigator judgment, patient has significant gastric bleeding and/or untreated gastric ulcers that would exclude the patient from participation per investigator Judgment
• Patient has any other condition, which, in the opinion of the treating physician, makes the patient unsuitable to receive or tolerate zolbetuximab.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Severance Hospital

Seoul, 03722, South Korea

RECRUITING

Related Publications (10)

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 RESULT

• Niimi T, Nagashima K, Ward JM, Minoo P, Zimonjic DB, Popescu NC, Kimura S. claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor, encodes lung- and stomach-specific isoforms through alternative splicing. Mol Cell Biol. 2001 Nov;21(21):7380-90. doi: 10.1128/MCB.21.21.7380-7390.2001.

  PMID: 11585919 RESULT

• Gunzel D, Yu AS. Claudins and the modulation of tight junction permeability. Physiol Rev. 2013 Apr;93(2):525-69. doi: 10.1152/physrev.00019.2012.

  PMID: 23589827 RESULT

• Sahin U, Koslowski M, Dhaene K, Usener D, Brandenburg G, Seitz G, Huber C, Tureci O. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res. 2008 Dec 1;14(23):7624-34. doi: 10.1158/1078-0432.CCR-08-1547.

  PMID: 19047087 RESULT

• Lee JH, Kim KS, Kim TJ, Hong SP, Song SY, Chung JB, Park SW. Immunohistochemical analysis of claudin expression in pancreatic cystic tumors. Oncol Rep. 2011 Apr;25(4):971-8. doi: 10.3892/or.2011.1132. Epub 2011 Jan 3.

  PMID: 21206985 RESULT

• Woll S, Schlitter AM, Dhaene K, Roller M, Esposito I, Sahin U, Tureci O. Claudin 18.2 is a target for IMAB362 antibody in pancreatic neoplasms. Int J Cancer. 2014 Feb 1;134(3):731-9. doi: 10.1002/ijc.28400. Epub 2013 Sep 16.

  PMID: 23900716 RESULT

• Sanada Y, Hirose Y, Osada S, Tanaka Y, Takahashi T, Yamaguchi K, Yoshida K. Immunohistochemical study of claudin 18 involvement in intestinal differentiation during the progression of intraductal papillary mucinous neoplasm. Anticancer Res. 2010 Jul;30(7):2995-3003.

  PMID: 20683045 RESULT

• Karanjawala ZE, Illei PB, Ashfaq R, Infante JR, Murphy K, Pandey A, Schulick R, Winter J, Sharma R, Maitra A, Goggins M, Hruban RH. New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8. Am J Surg Pathol. 2008 Feb;32(2):188-96. doi: 10.1097/PAS.0b013e31815701f3.

  PMID: 18223320 RESULT

• Shah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, Lordick F, Van Cutsem E, Gallego Plazas J, Huang J, Shen L, Oh SC, Sunpaweravong P, Soo Hoo HF, Turk HM, Oh M, Park JW, Moran D, Bhattacharya P, Arozullah A, Xu RH. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023 Aug;29(8):2133-2141. doi: 10.1038/s41591-023-02465-7. Epub 2023 Jul 31.

  PMID: 37524953 RESULT

• Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, Van Cutsem E, Xu RH, Aprile G, Xu J, Chao J, Pazo-Cid R, Kang YK, Yang J, Moran D, Bhattacharya P, Arozullah A, Park JW, Oh M, Ajani JA. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023 May 20;401(10389):1655-1668. doi: 10.1016/S0140-6736(23)00620-7. Epub 2023 Apr 15.

  PMID: 37068504 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

* Treatment effectiveness in the real world (progression-free survival, overall survival, response rate, etc.) * Adverse effects will be evaluated according to the NCI CTCAE v5.0 * Tissue samples collected before treatment, during treatment, and at disease progression will be analyzed using multiplex IHC to assess PD-L1 expression, MMR gene status, and Claudin18.2. Additionally, NGS testing will be conducted to evaluate the correlation with the treatment response to zolbetuximab. * Blood samples will be collected before treatment, during treatment, and after treatment completion to analyze ctDNA, scRNAseq, or immune cell profiling.

Study Officials

• Sun Young Rha

  Severance Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sun Young Rha

CONTACT

82-2-2227-8406; Rha7655@yuhs.ac

minkyu Jung

CONTACT

82-2-2227-8406; minkjung@yuhs.ac

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: December 24, 2024
• First Posted: January 9, 2025
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 9, 2025

Record last verified: 2025-01

Locations

KR (1)