Zolbetuximab Plus mFOLFOX for CLDN18.2+/HER2- Advanced Gastric/GEJ Cancers


Samuel Klempner, MD, explains the rationale for the phase 3 SPOTLIGHT study.

Samuel Klempner, MD, gastrointestinal medical oncologist, Oncology, Massachusetts General Hospital and faculty, Medicine, Harvard Medical School, explains the rationale for the phase 3 SPOTLIGHT study (NCT03504397) of zolbetuximab administered with 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) versus with placebo plus mFOLFOX6.

Klempner presented results from the study were presented during the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposium (ASCO GI). In the study, zolbetuximab achieved a significant improvement in progression-free survival (median 10.61) compared with mFOLFOX and placebo (median 8.67). Zolbetuximab also showed an overall survival advantage. Toxicity was not significantly increased by adding zolbetuximab to mFOLFOX vs placebo.


0:07 | The whole field of stomach and esophageal cancers is moving towards biomarker selection strategies, and this is great for patients. It helps us match patients to drugs that are ideally suited to have the greatest chance of benefit. That's the idea behind it. The SPOTLIGHT trial, which was presented at ASCO GI 2023, is the latest addition to the biomarker world of gastric and GEJ adenocarcinomas.

0:39 | There were some earlier clues about the activity of this approach in prior work. CLDN18.2 is overexpressed to varying levels in a large portion of patients with stomach and esophageal cancer. It’s seen in roughly around 40% of patients, depending on what cut off you use. There was a prior trial using monoclonal antibody against CLDN18.2 in combination with an anthracycline-based chemotherapy. It showed that the patients who got the zolbetuximab precursor in this case, IMAB362, added to chemotherapy had an improved survival. It was a phase 2 trial called the FAST study [NCT01630083]. It suggested that this strategy of targeting CLDN-high patients for treatment with a CLDN-directed antibody was something that had a lot of potential. That was the background and rationale for the phase 3 SPOTLIGHT trial presented at ASCO GI 2023.

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