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Background <p>Patients with gastric and pancreatic cancers, as well as other solid tumors including ovarian, lung, liver, and colon cancers, often lack effective therapeutic options. Claudin 18.2 (CLDN18.2) is a tumor-associated target that is predominantly expressed in gastric and pancreatic cancers but also found in several other tumor types. SOT102 is a novel antibody–drug conjugate directed against CLDN18.2, developed to provide a new therapeutic strategy for patients with CLDN18.2-positive tumors.</p> Methods <p>SOT102, composed of a proprietary monoclonal antibody (mAb) conjugated to the cytotoxic payload PNU-159682, was evaluated for binding, internalization, and cytotoxic effects in vitro. The in vivo antitumor activity was assessed in patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) mouse models, both as monotherapy and the latter in combination with anti-PD1 antibody therapy. SOT102 pharmacokinetics and tolerability were further investigated in cynomolgus monkeys following intravenous administration.</p> Results <p>SOT102 demonstrated selective binding to CLDN18.2, with no detectable cross-reactivity to CLDN18.1, and efficient internalization into CLDN18.2-expressing cell lines, resulting in potent cytotoxic effects against tumor organoids with half-maximal activity ranging from 0.2 nM to 19.4 nM. Antitumor activity against PDX-derived mouse models was observed at a minimum effective dose of 0.2&#xa0;mg/kg, with enhanced efficacy when combined with anti-PD1 antibody treatment. SOT102 exposure in cynomolgus monkeys was dose-dependent at doses between 0.3&#xa0;mg/kg and 1&#xa0;mg/kg with a half-life of approximately 7 days. An acceptable tolerability profile was observed, and the therapeutic window was defined between the minimum effective dose in mice and the highest non-severe toxic dose (HNSTD) of 0.6&#xa0;mg/kg in cynomolgus monkeys.</p> Conclusions <p>SOT102 exhibited strong antitumor activity in preclinical models of CLDN18.2-positive cancers and demonstrated a favorable pharmacokinetic and safety profile in non-human primates. These data were used to support clinical evaluation of SOT102 as a potential treatment option for patients with CLDN18.2-expressing solid tumors.</p>

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SOT102, a novel CLDN18.2-targeting antibody-drug conjugate, exhibits strong therapeutic potential in solid tumors

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Iva Valentová,
  • Lenka Kyrych Sadílková,
  • Lukas Bammert,
  • Lorenz Waldmeier,
  • Roger Beerli,
  • Ilona Procházková,
  • Filip Jabůrek,
  • Tatiana Spitzová,
  • Eliška Kohelová,
  • Kati Räsänen,
  • Ulrich Moebius,
  • Radek Špíšek

摘要

Background

Patients with gastric and pancreatic cancers, as well as other solid tumors including ovarian, lung, liver, and colon cancers, often lack effective therapeutic options. Claudin 18.2 (CLDN18.2) is a tumor-associated target that is predominantly expressed in gastric and pancreatic cancers but also found in several other tumor types. SOT102 is a novel antibody–drug conjugate directed against CLDN18.2, developed to provide a new therapeutic strategy for patients with CLDN18.2-positive tumors.

Methods

SOT102, composed of a proprietary monoclonal antibody (mAb) conjugated to the cytotoxic payload PNU-159682, was evaluated for binding, internalization, and cytotoxic effects in vitro. The in vivo antitumor activity was assessed in patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) mouse models, both as monotherapy and the latter in combination with anti-PD1 antibody therapy. SOT102 pharmacokinetics and tolerability were further investigated in cynomolgus monkeys following intravenous administration.

Results

SOT102 demonstrated selective binding to CLDN18.2, with no detectable cross-reactivity to CLDN18.1, and efficient internalization into CLDN18.2-expressing cell lines, resulting in potent cytotoxic effects against tumor organoids with half-maximal activity ranging from 0.2 nM to 19.4 nM. Antitumor activity against PDX-derived mouse models was observed at a minimum effective dose of 0.2 mg/kg, with enhanced efficacy when combined with anti-PD1 antibody treatment. SOT102 exposure in cynomolgus monkeys was dose-dependent at doses between 0.3 mg/kg and 1 mg/kg with a half-life of approximately 7 days. An acceptable tolerability profile was observed, and the therapeutic window was defined between the minimum effective dose in mice and the highest non-severe toxic dose (HNSTD) of 0.6 mg/kg in cynomolgus monkeys.

Conclusions

SOT102 exhibited strong antitumor activity in preclinical models of CLDN18.2-positive cancers and demonstrated a favorable pharmacokinetic and safety profile in non-human primates. These data were used to support clinical evaluation of SOT102 as a potential treatment option for patients with CLDN18.2-expressing solid tumors.