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Late-Breaking Abstracts
Clinical Trial In Progress
1472 A phase 1/2 study evaluating the safety and efficacy of autologous TAC T cells in subjects with claudin 18.2+ advanced solid tumors
  1. Ecaterina E Dumbrava1,
  2. Syma Iqbal2,
  3. Simon Turcotte3,
  4. Gregory Botta4,
  5. Benjamin Schlechter5,
  6. Geoffrey Ku6,
  7. Peter Hosein7,
  8. Sam Saibil8,
  9. Miriam Gavriliuc1,
  10. Maria Apostolopoulou9,
  11. Mobolaji Giwa9,
  12. Kara Moss9,
  13. Swaminathan Murugappan10 and
  14. Davendra Sohal11
  1. 1The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  2. 2USC Norris Comprehensive Cancer Ctr Div Onc, Los Angeles, CA, USA
  3. 3Université de Montréal, Montreal, QC, Canada
  4. 4University of California San Diego, La Jolla, CA, USA
  5. 5Dana-Farber Cancer Institute, Boston, MA, USA
  6. 6Memorial Sloan Kettering Cancer Center, New York, NY, USA
  7. 7University of Miami, Coral Gables, FL, USA
  8. 8University Health Network, Toronto, ON, Canada
  9. 9Triumvira Immunologics Inc., Austin, TX, USA
  10. 10Trident Bio Consulting Inc., San Ramon, CA, USA
  11. 11University of Cincinnati Cancer Center, Cincinnati, OH, USA

  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.

Abstract

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.

A 100% disease control rate was observed at first tumor assessment (Day 29) in the five eligible subjects for efficacy assessment. 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 (5 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.

Ethics Approval This study was approved by MD Anderson’s Ethics Board; approval number 2023-0146. This study was approved by University of Cincinatti’s Ethics Board (Advarra); approval number Pro00071206. This study was approved by University of Southern California Health Sciences’ Ethics Board; approval number #HS-23-00306. This study was approved by CHUM’s Ethics Board; approval number 23.178. This study was approved by University of California San Diego Health’s Ethics Board (Advarra); approval number Pro00071206. This study was approved by Dana Farber Cancer Insitute’s Ethics Board; approval number 24-088. This study was approved by Memorial Sloan Kettering Cancer Center’s Ethics Board; approval number 24-136. This study was approved by University of Miami’s Ethics Board; approval number 20231138. All subjects gave informed consent before participating.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/jitc-2024-SITC2024.1472

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