ESMO 2025 | Phase I/Ib trial of ASP2138 monotherapy in CLDN18.2+ advanced solid tumors

ASP213A is a bi-specific T-cell-engager agent which binds Claudin 10.2 and CD3 on lymphocytes. And it activates lymphocytes around Claudin-positive tumor cells and because of the release of cytokine, it results in cancer cell killing. So this agent targeted Claudin 10.2 because it is already established to target in gastric cancer because of previous phase three trial of Zolbetuximab, which improved overall survival with chemo plus Zolbetuximab. Zolbetuximab is an IgG monoclonal antibody, which activates NK cell macrophage to induce ADCC, CDC, and ADCP, and different from ASP213A, which activates lymphocytes. So that is an important rationale to develop this agent for Claudin-positive tumors. And in this phase one trial, we evaluate a single agent, safety, as well as activity. We especially test both subcutaneous infusion and IV infusion. So first post which I presented in this ESMO is regarding IV infusion, which enrolled both gastric and PDAC population. First, safety profile is within acceptable range. Around 30% of patients experience cytokine release syndrome, CRS. Most of them were with grade one and grade two and were controlled by established management protocol. And other common events were GI toxicity like nausea and vomiting. It is not easy to conclude but a little bit lower than that observed with taximab in terms of incidence. The overall efficacy is not high in terms of response rate but 10% of patients achieved response and this was observed regardless of Claudin expression and around 30% additional patients achieved disease control. And interestingly, there is a trend of a higher PK or dose and a better disease control rate, which led to us to conclude one dose as established recommended dose. And then we also tested subcutaneous infusion, which also showed a very similar safety and efficacy profile. Subcutaneous infusion is a little bit less frequency of cytokine release syndrome and better to combine with first-line chemotherapy and second-line chemotherapy. So we combined it with first-line FOLFOX plus Pembrolizumab and Paclitaxel plus Ramucirumab. And both combinations showed acceptable safety profiles. Also, we observed the toxicity which reflects each component of chemotherapy and ASP213A as well as Pembrolizumab in front-line, but overall manageable. Interestingly, more patients associated with gastritis with secondary Paclitaxel and Ramucirumab, but at this stage, we are not sure whether this is a cluster effect, especially combination with Paclitaxel or Ramucirumab, or just based on relatively small sample size. So we need to carefully follow up with additional patients. And efficacy is very promising with more than 60% response rate with first line and more than 30% in second line, but we need additional follow-up to see additional efficacy results.

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