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738 A phase 1/2 study investigating the safety and efficacy of autologous TAC T cells in subjects with unresectable, locally advanced or metastatic claudin 18.2+ solid tumors
  1. Daniel J Olson1,
  2. Ecaterina Dumbrava2,
  3. Sam Saibil3,
  4. Martin Gutierez4,
  5. Syma Iqbal5,
  6. Davendra Sohal6,
  7. Maria Apostolopoulou7,
  8. Kara Moss8,
  9. Deyaa Adib8 and
  10. Benjamin Schlechter9
  1. 1University of Chicago, Chicago, IL, USA
  2. 2The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  3. 3University Health Network Princess Margaret, Toronto, ON, Canada
  4. 4Hackensack University Medical Center, Hackensack, NJ, USA
  5. 5Usc Norris Comprehensive Cancer Ctr Div Onc, Los Angeles, CA, USA
  6. 6University of Cincinnati Cancer Center, Cincinnati, OH, USA
  7. 7Triumvira Immunologics Inc., Falmouth, MA, USA
  8. 8Triumvira Immunologics, Austin, TX, USA
  9. 9Dana-Farber Cancer Institute, Boston, MA, USA


Background CLDN18.2 is a tight junction protein found in differentiated gastric epithelial cells which can become abnormally or ectopically expressed in a number of solid tumor indications. This exposure profile illustrates the potential of CLDN18.2 as a candidate for targeted therapy. To date, there are no approved therapeutic agents directed against this target.

The T cell antigen coupler (TAC) technology is an approach to modifying T cells ex vivo, which allows recognition and cytotoxicity of tumor cells by co-opting the natural T cell receptor. TAC T cells demonstrate a safer profile than chimeric antigen receptor T cells. TAC01-CLDN18.2 is an autologous T-cell product comprising T cells expressing CLDN18.2 TAC.

Methods This is a first-in-human study (NCT05862324) to investigate the safety and preliminary anti-tumor activity of TAC01-CLDN18.2 in CLDN18.2+/HER2- solid tumors. Subjects will undergo leukapheresis and may receive bridging anticancer therapy, if deemed necessary by the Investigator, during cell manufacturing. Prior to TAC01-CLDN18.2 infusion, subjects will undergo low-intensity lymphodepletion chemotherapy.

In phase I dose escalation, TAC01-CLDN18.2 will be administered at increasing doses (Cohorts 1–3) in adult subjects after ≥2 lines of therapy using the classic 3+3 dose escalation study design. Subjects with pancreatic ductal adenocarcinoma (PDAC) may have been treated with 1 line of prior therapy. CLDN18.2 expression levels will be determined centrally using a clinical trial assay validated across relevant indications. Dose limiting toxicities will be assessed up to 28 days from TAC01-CLDN18.2 infusion. A second dose may be administered, according to preidentified clinical and safety criteria.

In Phase II, dose expansion groups will further evaluate the efficacy, safety, and pharmacokinetics of the optimal TAC01-CLDN18.2 dose, with the option of redosing. Indications will include gastric and esophageal adenocarcinoma (group A), PDAC (group B) and ovarian and non-small cell lung cancer (group C) in subjects after ≥2 and <4 lines of prior therapy (subjects with PDAC may have been exposed to 1 therapy). Definitions of eligible CLDN18.2 expression levels will be based on retrospective analysis of data from Phase 1 in association with clinical efficacy. A Simon 2-stage design will be used to enroll ≤57 subjects in Group A and ≤22 subjects in Group C. Group B will be exploratory and will enroll ≤10 subjects with an opportunity of cohort enrichment based on clinical efficacy data.

Trial Registration NCT05862324

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