How would you treat newly diagnosed stage IV GEJ adenocarcinoma with both Claudin 18.2 and HER2 (3+ via IHC) overexpression?

Would treat as any other HER+3. FOLFOX+Trastuzumab and add pembrolizumab only if PDL1+. Given the lack of data, would not add zolbe.

At present, I would use the HER-2-directed antibodies and ADCs for the treatment of this patient. The Zolbetuximab studies have specifically excluded patients with HER-2 overexpressing gastric cancers. Therefore, we do not have any data to know if anti-Claudin antibodies are as effective in this group of patients as in the patient studies to date. Additionally, there are no studies published on the use of Zolbetuximab in HER-2 overexpressing patients or ongoing studies with the combination of antibodies in those with HER-2 overexpression.

In short, this would be off-label use (alone or in combination with trastuzumab) and no data is available to inform us as to how effective the Claudin antibody would be.