Article Text

Download PDFPDF

654 A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors
  1. Daniel J Olson1,
  2. Ecaterina Dumbrava2,
  3. Mridula George3,
  4. Sam Saibil4,
  5. Marcus Butler4,
  6. Antonio Giordano2,
  7. Brooke Pieke1,
  8. Miriam Gavriliuc2,
  9. Emily Lichtenstein3,
  10. Jill Geisberger4,
  11. Maria Apostolopoulou6,
  12. Kara Moss7,
  13. D’Arcy Kirkwood7,
  14. Salina Dang7,
  15. Deyaa Adib7 and
  16. Benjamin Schlechter5
  1. 1University of Chicago, Chicago, IL, USA
  2. 2The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  3. 3Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
  4. 4University Health Network Princess Margaret, Toronto, ON, Canada
  5. 5Dana-Farber Cancer Institute, Boston, MA, USA
  6. 6Triumvira Immunologics Inc., Falmouth, MA, USA
  7. 7Triumvira Immunologics, Austin, TX, 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.


Background Despite therapeutic developments for patients with advanced HER2+ solid tumors, significant unmet medical needs still exist. 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-HER2 is an autologous T-cell product comprising T cells expressing HER2 TAC.

Methods The ongoing clinical trial (NCT04727151) is evaluating the safety and preliminary anti-tumor activity of TAC01-HER2 treatment of HER2+ solid tumors. Subjects undergo leukapheresis followed by low-intensity lymphodepletion chemotherapy prior to TAC01-HER2 infusion.

In phase I dose escalation, TAC01-HER2 is administered at increasing doses (Cohorts 1–4) in adult subjects after ≥2 lines of therapy. Dose limiting toxicities (DLT) are assessed up to 28 days from TAC01-HER2 infusion.

In Phase II, dose expansion groups will further evaluate the efficacy, safety, and pharmacokinetics of the optimal TAC01-HER2 dose in gastric/GEJ tumors.

Results As of 5 June 2023, 20 patients with solid tumors have been treated in Cohorts 1–4. Three were HER2 1+ or 2+/FISH-. One DLT event of grade (G) 3 pneumonitis has been reported in 1 subject in Cohort 4. No neurotoxicity has been reported. Most subjects treated at Cohorts 3–4 experienced cytokine release syndrome (CRS) which resolved with supportive therapy. Thirteen subjects have reported a total of 26 serious adverse events, with 1 G3 pneumonitis, 4 CRS (1 G1, 3 G2 and 1 G3) and 1 G3 bronchial hyperreactivity related to TAC01-HER2.

A 67% disease control rate (DCR) was observed in Cohorts 2–4 at first restaging after TAC01-HER2 infusion. For gastric/GEJ subjects of the same Cohorts, DCR was 83%. 3 months after TAC01-HER2 infusion, DCR was 33.3% for all subjects of Cohorts 2–4 and 50% for gastric/GEJ subjects. Two patients had a partial response (PR). At Cohort 4, a PR was observed in a subject with GEJ (HER2 2+, FISH+) with 100% reduction of target lesion. This patient had progressed on 4 prior lines of therapy including trastzumab and trastuzumab deruxtecan.

Conclusions Treatment with TAC01-HER2 showed manageable safety and promising clinical activity in a heavily pre-treated cancer population. The recommended phase 2 dose was identified as dose level 4 (6–8 x 106 cells/kg).

Trial Registration, NCT04727151

Ethics Approval This study obtained ethics approval from the following IRBs:

  • UHN, #21-5026

  • Rutgers, #Pro2021002270

  • MD Anderson Cancer Center, #2020-1161_MOD007

  • University of Chicago, #IRB20-1944-AM005

  • Dana Farber Cancer Institute, #21-062

All participants gave informed consent before participating in this study.

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

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.