Clinical trial NCT06767449: Zolbetuximab Claudin18.2 Positive, HER2 Negative, Advanced Gastric Cancer
Official title: Multi-center Cohort Study to Evaluate the Real-world Efficacy and Safety of Zolbetuximab Plus Chemotherapy in Claudin18.2 Positive, HER2 Negative, Advanced Gastric Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Advanced Gastric Cancer
Keywords: Zolbetuximab
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2025-01-09
Enrollment: 80
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

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.

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.

Primary outcomes:
measure: Treatment effectiveness
timeFrame: 2 year
measure: Number of participants with treatment-related adverse events as assessed by CTCAE V5.0
timeFrame: 2 year
measure: molecular marker Analysis
timeFrame: 2 year
Secondary outcomes:
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
affiliation: Severance Hospital
name: Sun Young Rha
role: PRINCIPAL_INVESTIGATOR
References:
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