ILUSTRO: Phase II multicohort trial of zolbetuximab in patients with advanced or metastatic claudin 18.2–positive gastric or gastroesophageal junction adenocarcinoma Journal Article
| Authors: | Klempner, S. J.; Lee, K. W.; Shitara, K.; Metges, J. P.; Lonardi, S.; Ilson, D. H.; Fazio, N.; Kim, T. Y.; Bai, L. Y.; Moran, D.; Yang, J.; Arozullah, A.; Park, J. W.; Raizer, J. J.; Bang, Y. J.; Shah, M. A. |
| Article Title: | ILUSTRO: Phase II multicohort trial of zolbetuximab in patients with advanced or metastatic claudin 18.2–positive gastric or gastroesophageal junction adenocarcinoma |
| Abstract: | 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 1⁄4 30), with mFOLFOX6 in first-line (Cohort 2, n 1⁄4 21), or with pembrolizumab in third/later-line (Cohort 3A, n 1⁄4 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. ©2023 The Authors; Published by the American Association for Cancer Research. |
| Keywords: | adult; clinical article; treatment outcome; aged; survival rate; unclassified drug; overall survival; clinical feature; clinical trial; constipation; fatigue; neutropenia; paresthesia; fluorouracil; advanced cancer; cancer combination chemotherapy; diarrhea; dose response; drug efficacy; drug safety; hypertension; monotherapy; antineoplastic agent; adenocarcinoma; progression free survival; phase 2 clinical trial; sensory neuropathy; anemia; nausea; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; myalgia; peripheral neuropathy; epidermal growth factor receptor 2; cohort analysis; continuous infusion; drug effect; pathology; risk factor; monoclonal antibody; abdominal pain; asthenia; backache; coughing; dizziness; fever; loading drug dose; pruritus; dysphagia; hypokalemia; antibodies, monoclonal; adverse outcome; folinic acid; clinical effectiveness; oxaliplatin; dyspepsia; muscle spasm; stomach adenocarcinoma; stomach neoplasms; esophagus tumor; esophageal neoplasms; stomach tumor; hematemesis; esophagogastric junction; decreased appetite; gastroesophageal junction adenocarcinoma; gastroesophageal junction; claudin; humans; human; male; female; article; pembrolizumab; claudin 18.2; claudins; gastrointestinal adenocarcinoma; claudin 18; adenocarcinoma of esophagus; cldn18 protein, human; zolbetuximab |
| Journal Title: | Clinical Cancer Research |
| Volume: | 29 |
| Issue: | 19 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2023-10-01 |
| Start Page: | 3882 |
| End Page: | 3891 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-23-0204 |
| PUBMED: | 37490286 |
| PROVIDER: | scopus |
| PMCID: | PMC10543966 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
