What information is available on the GLEAM trial?

Published

Phase 2, open-label, randomized study of zolbetuximab + chemotherapy as first-line treatment for CLDN18.2-positive, metastatic pancreatic adenocarcinoma

  • GLEAM1 (NCT03816163) is assessing zolbetuximab + gemcitabine and nab-paclitaxel (GN) compared with GN alone in 393 adult patients. A total of 2529 patients with metastatic pancreatic cancer were screened
  • At final analysis, zolbetuximab + GN did not meet the primary endpoint of overall survival or extend progression free survival compared to GN alone
  • Zolbetuximab + GN showed a numerically higher objective response rate (∆ = 7.3%) and longer duration of response (∆ = 2.0 months) compared with GN alone despite a similar overall disease control rate
  • No new safety signals emerged for zolbetuximab
  • Serious treatment emergent adverse events (TEAEs) occurred in 73.7% of patients treated with zolbetuximab + GN compared with 53.9% in GN alone. TEAEs led to permanent treatment discontinuation in 37.1% of patients, with nausea (8.5%) and vomiting (8.1%) being the most common causes of early treatment discontinuation

Figure 1. Clinical trial design1

Key endpoints in bold. aBased on RECIST version 1.1. bdetermined by central IHC testing
1. ClinicalTrials.gov. NCT03816163. https://clinicaltrials.gov/study/NCT03816163. Accessed 16 June 2026.

C, cycle; CA 19-9, Carbohydrate antigen 19-9; CLDN18.2, Claudin 18 isoform 2; D, day; DCR, Disease control rate; DOR, Duration of response; ECOG PS, Eastern Cooperative Oncology Group Performance Score; EORTC, European Organisation for Research and Treatment of Cancer; EQ-5D-5L, EuroQol 5-Dimension 5-Level questionnaire; GEM, Gemcitabine; GN, Gemcitabine + Nab-paclitaxel; IHC, Immunohistochemistry; IV, Intravenous; mPAC, Metastatic pancreatic ductal adenocarcinoma; Nab-P, Nanoparticle albumin-bound paclitaxel; ORR, Objective response rate; OS, Overall Survival; PFS, Progression Free Survival; PGIC, Patient Global Impression of Change; PGIS, Patient Global Impression of Severity; PK, Pharmacokinetics; Q2W, once every 2 weeks; QLQ-C30, Quality of Life Questionnaire Core 30; QLQ-PAN26, Quality of Life Questionnaire Pancreatic Ductal Adenocarcinoma 26; R, Randomized; RECIST, Response Evaluation Criteria in Solid Tumors; R2PD, Recommended phase 2 dose

Figure 2. Kaplan-Meier curve – Primary endpoint (OS) not met1

Data cutoff: September 3, 2025. Full analysis set. + indicates censored patients.

CI, Confidence interval; CLDN18.2, Claudin 18 isoform 2; GN, Gemcitabine + Nab-paclitaxel; HR, Hazard Ratio; mPAC, Metastatic pancreatic ductal adenocarcinoma; OS, Overall survival; Pts, Patients.

  1. Park W, Shen L, Ducreux M, et al. Zolbetuximab plus gemcitabine and nab-paclitaxel in patients with claudin 18 isoform 2 (CLDN18.2)+ metastatic pancreatic adenocarcinoma (mPAC): Phase II GLEAM study [oral slide presentation]. European Society for Medical Oncology Gastrointestinal Cancers Annual Meeting. Munich, Germany. 2026. 
find-my-msl

Find My MSL

Medical Science Liaisons are available to help answer your scientific questions.

submit

Submit an Inquiry

For any medical inquiries, please submit your question online to Astellas Medical Information or call or fax your inquiry.

Astellas Phone: 1-800-727-7003

Fax: 1-877-829-7942

adverse

Report an Adverse Event or Product Complaint

Report adverse events and product complaints to Astellas or FDA MedWatch.

Astellas Phone: 1-800-727-7003

FDA MedWatch: 1-800-FDA-1088

Hours: M–F, 8 AM–4:30 PM (CT)