Should zolbetuximab loading dose be repeated after interruptions?

Published

Prescribing Information including BOXED WARNING

No guidance on repeating loading dose; in Phase 3 trials, patients with delays >49 days stopped treatment, patients with delays ≤49 days resumed 600 mg/m² dose

In the Phase 3 clinical trials GLOW and SPOTLIGHT, zolbetuximab was given as a single 800 mg/m² loading dose on Cycle 1 Day 1, followed by 600 mg/m² every three weeks with fluoropyrimidine- and platinum-based chemotherapy until treatment discontinuation criteria were met.^1,2

A population pharmacokinetic (PopPK) and exposure–response analysis found similar efficacy and safety with the 800/600 mg/m² every three-week regimen and the 800/400 mg/m² every two-week regimen when used in combination with chemotherapy.³

Further details on the analysis can be accessed using the link below.

Zolbetuximab - Assessment of Alternative Dosing Regimen

The elimination half-life of zolbetuximab ranged from 7.56 to 15.2 days during treatment, based on a population pharmacokinetic and exposure-response analysis.³

Treatment decisions should follow the judgment of the healthcare provider and institutional protocols.

Shah MA, Shitara K, Ajani JA, et al. Supplement to: Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29(8):2133-2141. Available at: https://doi.org/10.1038/s41591-023-02465-7.
Shitara K, Lordick F, Bang YJ, et al. Supplement to: 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;401(10389):1655-1668. Available at: https://doi.org/10.1016/s0140-6736(23)00620-7.
Yamada A, Takeuchi M, Komatsu K, et al. Population PK and Exposure‐Response Analyses of Zolbetuximab in Patients With Locally Advanced Unresectable or Metastatic G/GEJ Adenocarcinoma. Clin. Transl. Sci. 2025;18(7):e70280. Available at: https://doi.org/10.1111/cts.70280.