Zolbetuximab Reaches PFS End Point in CLDN18.2+ HER2– Advanced/Metastatic Gastric/GEJ Adenocarcinoma


Zolbetuximab and mFOLFOX6 combination therapy demonstrated positive topline efficacy and safety in patients with Claudin 18.2–positive, HER2-negative gastric or gastroesophageal junction adenocarcinoma.

Topline results from the phase 3 SPOTLIGHT study (NCT03504397) indicated that zolbetuximab (IMAB362) plus modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) met the primary end point of progression-free survival (PFS) in patients with Claudin 18.2 (CLDN18.2)–positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to a press release from Astellas.

In the trial, zolbetuximab plus mFOLFOX6 demonstrated a statistically significant improvement in PFS, as well as the secondary end point of overall survival (OS) compared with placebo plus mFOLFOX6. The most common treatment-emergent adverse effects among treated patients included nausea, vomiting, and decreased appetite. Detailed results from the trial will be presented at a later scientific congress and submitted for publication.

“I am excited by the potential for a new treatment option to help patients with advanced-stage gastric cancer or GEJ cancer,” primary investigator Kohei Shitara, MD, chief in the Department of Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan, said in the press release. “Gastric and GEJ cancers still have very limited treatment options available for patients with an advanced diagnosis.”

Zolbetuximab is an investigational monoclonal antibody that targets and binds to CLDN18.2 on the cell cancer surface, inducing cell death by activating 2 immune pathways: antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.

The global, multicenter, double-blind, randomized phase 3 SPOTLIGHT study was designed to compare the efficacy and safety of zolbetuximab and mFOLFOX6 combination therapy with placebo plus mFOLFOX6 in the first-line treatment of patients with CLDN18.2-positive, HER2-negative, advanced or metastatic gastric or GEJ cancer. A total of 566 patients were enrolled across 220 study locations in the United States, United Kingdom, Australia, Europe, South America, and Asia.

Secondary end points of the SPOTLIGHT study included objective response rate, duration of response, health-related quality-of-life measured by the European Organization for Research and Treatment of Cancer questionnaire, the pharmacokinetics of zolbetuximab, and the number of anti-drug antibody–positive patients.

Adult patients with a histologically confirmed diagnosis of gastric or GEJ adenocarcinoma were eligible to enroll on the study. Additional inclusion criteria included having radiologically confirmed locally advanced unresectable or metastatic disease, tumors expressing CLDN18.2 in at least 75% of tumor cells, a HER-2 negative tumor, an ECOG performance status of 0 or 1, and a predicted life expectancy of at least 12 weeks.

Patients were unsuitable for enrollment if they received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. Patients were also unsuitable for enrollment if they received radiotherapy or systemic immunosuppressive therapy within 14 days prior to randomization, received other investigational therapies within 28 days of randomization, had prior severe allergic reactions to known ingredients of zolbetuximab or other monoclonal antibodies, or had a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent or recurrent vomiting.


Astellas announces zolbetuximab meets primary endpoint in phase 3 SPOTLIGHT trial as first-line treatment in Claudin 18.2 positive, HER2-negative locally advanced or metastatic gastric and gastroesophageal junction (GEJ) cancers. News release. Astellas Pharma Inc. November 17, 2022. Accessed November 17, 2022. bit.ly/3EFTdWQ

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