A phase 1/2 study evaluating the safety and efficacy of autologous TAC T cells in subjects with claudin 18.2+ advanced solid tumors.
Bibliographic record
Abstract
828 Background: Claudin18.2 (CLDN18.2) is a tight junction protein found in gastric epithelial cells. It can become abnormally expressed in gastric cancer and other solid tumors, rendering it a candidate for targeted therapy. There are no approved therapeutic agents against CLDN18.2. The T cell antigen coupler (TAC) technology modifies T cells ex vivo , allowing 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: In this first-in-human study (NCT05862324), subjects will undergo leukapheresis and may receive bridging anticancer therapy during cell manufacturing. Prior to TAC01-CLDN18.2 infusion, subjects will undergo lymphodepletion chemotherapy. In Phase I, TAC01-CLDN18.2 will be administered at increasing doses (3 cohorts) in adult subjects with ≥2 lines of prior therapy (1 for subjects with pancreatic ductal adenocarcinoma (PDAC)) using the classic 3+3 dose escalation study design. CLDN18.2 expression levels will be determined centrally using a validated clinical trial assay. Dose-limiting toxicities (DLTs) will be assessed up to 28 days after the infusion. A second dose may be administered according to preidentified clinical and safety criteria. In Phase II, dose expansion groups will 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 with <4 lines of prior therapy. Results: The first two dose cohorts of Phase I have been completed, with no reported dose-limiting toxicities (DLT). All of the TAC-related adverse events were low-grade. No cytokine release syndrome was reported. One subject in cohort 2 experienced a grade 1 neurotoxicity, which resolved the same day without intervention. Six subjects reported a total of 6 serious adverse events, none related to TAC01-CLDN18.2. An 83.3% disease control rate was observed at first tumor assessment (Day 29). One subject in cohort 1 with heavily pre-treated PDAC (3 prior lines) with high CLDN18.2 expression has an ongoing, confirmed partial response. The subject received a second dose and is still on treatment (6 months). Conclusions: Treatment with the lower doses of TAC01-CLDN18.2 is safe and shows promising clinical activity in a heavily pre-treated cancer population. Treatment of cohort 3 has begun. Clinical trial information: NCT05862324 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".