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ILUSTRO: Phase II Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma.

Publication ,  Journal Article
Klempner, SJ; Lee, K-W; Shitara, K; Metges, J-P; Lonardi, S; Ilson, DH; Fazio, N; Kim, TY; Bai, L-Y; Moran, D; Yang, J; Arozullah, A ...
Published in: Clin Cancer Res
October 2, 2023

PURPOSE: Zolbetuximab, an IgG1 monoclonal antibody, binds to claudin 18.2 (CLDN18.2) and mediates tumor cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. We sought to examine zolbetuximab combinations in CLDN18.2-positive HER2-negative gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. PATIENTS AND METHODS: This phase II study assessed efficacy and safety of zolbetuximab, alone or with modified FOLFOX6 (mFOLFOX6) or pembrolizumab, in CLDN18.2-positive advanced/metastatic G/GEJ adenocarcinoma. Patients received zolbetuximab as monotherapy in third/later-line (Cohort 1A, n = 30), with mFOLFOX6 in first-line (Cohort 2, n = 21), or with pembrolizumab in third/later-line (Cohort 3A, n = 3) treatment. The primary endpoint for Cohort 1A was objective response rate (ORR). Key secondary endpoints were ORR (Cohorts 2 and 3A), overall survival (OS; Cohort 1A), and progression-free survival (PFS) and safety (all cohorts). RESULTS: ORR was 0% in Cohorts 1A and 3A, and 71.4% [95% confidence interval (CI), 47.82-88.72] in Cohort 2. Median PFS was 1.54 months (95% CI, 1.31-2.56) in Cohort 1A, 2.96 months (95% CI, 1.48-4.44) in Cohort 3A, and 17.8 months (95% CI, 8.05-25.69) in Cohort 2. Median OS in Cohort 1A was 5.62 months (95% CI, 2.27-11.53). Gastrointestinal adverse events occurred across cohorts [nausea, 63%-90% (grade ≥ 3, 4.8%-6.7%) and vomiting, 33%-67% (grade ≥ 3, 6.7%-9.5%)]. CONCLUSIONS: Zolbetuximab plus mFOLFOX6 demonstrated promising efficacy in previously untreated patients with CLDN18.2-positive G/GEJ adenocarcinoma. These data support the first-line development of zolbetuximab in patients whose tumors are CLDN18.2-positive. Across cohorts, zolbetuximab treatment was tolerable with no new safety signals.

Duke Scholars

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

October 2, 2023

Volume

29

Issue

19

Start / End Page

3882 / 3891

Location

United States

Related Subject Headings

  • Stomach Neoplasms
  • Oncology & Carcinogenesis
  • Humans
  • Esophagogastric Junction
  • Esophageal Neoplasms
  • Claudins
  • Antineoplastic Combined Chemotherapy Protocols
  • Antibodies, Monoclonal
  • Adenocarcinoma
  • 3211 Oncology and carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Klempner, S. J., Lee, K.-W., Shitara, K., Metges, J.-P., Lonardi, S., Ilson, D. H., … Shah, M. A. (2023). ILUSTRO: Phase II Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res, 29(19), 3882–3891. https://doi.org/10.1158/1078-0432.CCR-23-0204

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

October 2, 2023

Volume

29

Issue

19

Start / End Page

3882 / 3891

Location

United States

Related Subject Headings

  • Stomach Neoplasms
  • Oncology & Carcinogenesis
  • Humans
  • Esophagogastric Junction
  • Esophageal Neoplasms
  • Claudins
  • Antineoplastic Combined Chemotherapy Protocols
  • Antibodies, Monoclonal
  • Adenocarcinoma
  • 3211 Oncology and carcinogenesis