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

NCT ID: NCT06767449

Last Updated: 2025-01-09

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2026-12-01

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)

Detailed Description

• 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.

Conditions

Advanced Gastric Cancer

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

1. Patient is ≥ 19 years of age at the time of consent.

2. The patient must have histologically confirmed locally advanced, unresectable, or metastatic gastric or gastroesophageal junction adenocarcinoma

3. 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.

4. The tumor sample must be HER2-negative (IHC 0, 1+, or IHC 2+/ISH-).

5. The patient must have received Zolbetuximab as a first-line treatment.

6. 1 Patient has ECOG performance status 0 or 1.

7. 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

Exclusion Criteria

1. 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

2. History of known or suspected hypersensitivity to Zolbetuximab, other monoclonal antibodies, or components of the used formulations.

3. 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.

4. 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.

5. Patient has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting

6. Per investigator judgment, patient has significant gastric bleeding and/or untreated gastric ulcers that would exclude the patient from participation per investigator Judgment

7. Patient has any other condition, which, in the opinion of the treating physician, makes the patient unsuitable to receive or tolerate zolbetuximab.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Sun Young Rha

PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sun Young Rha

Role: PRINCIPAL_INVESTIGATOR

Severance Hospital

Locations

Severance Hospital

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Sun Young Rha

Role: CONTACT

Rha7655@yuhs.ac

82-2-2227-8406

minkyu Jung

Role: CONTACT

minkjung@yuhs.ac

82-2-2227-8406

References

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.

Reference Type: RESULT

PMID: 33538338 (View on PubMed)

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.

Reference Type: RESULT

PMID: 11585919 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23589827 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19047087 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21206985 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23900716 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20683045 (View on PubMed)

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.

Reference Type: RESULT

PMID: 18223320 (View on PubMed)

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.

Reference Type: RESULT

PMID: 37524953 (View on PubMed)

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.

Reference Type: RESULT

PMID: 37068504 (View on PubMed)

Other Identifiers

4-2024-1274

Identifier Type: -

Identifier Source: org_study_id