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760 A phase I/II trial investigating safety and efficacy of autologous TAC T cells targeting HER2 in relapsed or refractory solid tumors
  1. Benjamin Schlechter1,
  2. Daniel Olson2,
  3. Samuel Saibil3,
  4. Mridula George4,
  5. Riemke Bouvier1,
  6. Jessica McKinley5,
  7. Brooke Pieke2,
  8. Jill Geisburger6,
  9. Nathan Ternus7,
  10. Kara Moss7,
  11. Deyaa Adib7 and
  12. Ecaterina Dumbrava5
  1. 1Dana Farber Cancer Institute, Boston, MA, USA
  2. 2University of Chicago, Chicago, IL, USA
  3. 3Princess Margaret Cancer Center, Toronto, Canada
  4. 4Rutgers University, New Brunswick, NJ, USA
  5. 5MD Anderson Cancer Center, Houston, TX, USA
  6. 6Princess Margaret Cancer Center – UHN, Toronto, Canada
  7. 7Triumvira Immunologics, Austin, TX, USA


Background Despite recent therapeutic developments for patients with advanced, metastatic, unresectable HER2 positive (HER2+) solid tumors, significant unmet medical needs still exist, especially in tumors other than breast and gastric cancers and in patients with HER2-low expression. The T cell antigen coupler (TAC) technology is a novel approach to modifying T cells, allowing them to recognize and treat HER2+ solid tumors. Mechanistically, the TAC receptor redirects T cells to tumor cells, and upon recognition, co–opts the natural T cell receptor (TCR) signaling action to yield safe anti-tumor responses. In preclinical studies, TAC T cells led to complete tumor clearance in various human HER2+ mouse models, without any TAC-related toxicities, and results superior to a similar 2nd generation chimeric antigen receptor (CAR) T cell.

In this ongoing clinical trial (NCT04727151), subjects undergo leukapheresis, bridging therapy while their TAC T cells are engineered (if needed), lymphodepletion chemotherapy (LDC), and finally TAC01-HER2 infusion.

Methods Dose escalation in Phase 1 is investigating the safety and tolerability of TAC01-HER2 single doses of 0.08, 0.3 (starting dose), 0.8, 3, 8 x 106 cells/kg in adult subjects with HER2+ solid tumors (1+, 2+ or 3+ by immunohistochemistry) who have progressed after ≥2 lines of systemic therapy. Dose limiting toxicities (DLTs) are being assessed up to 28 days after TAC01-HER2 infusion.

In Phase 2, dose expansion groups will further evaluate the safety, efficacy, and pharmacokinetics of the optimal TAC01-HER2 dose in HER2+ breast and other HER2+ tumor types, including: lung, pancreatic, colorectal, gastric, endometrial, and ovarian.

As of 20 July 22, eight subjects have been treated in Cohorts 1 and 2, with no DLTs or events of special interest, such as cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome, being observed. Four subjects had 8 serious adverse events; all unrelated to TAC01-HER2 infusion and attributed to LDC or underlying malignancies. Preliminary safety results indicate single TAC01-HER2 treatments in a heavily pre-treated population have been well-tolerated, with the most frequent adverse events (AEs) being cytopenias related to LDC. Continued dose escalation of TAC01-HER2 is ongoing.

Following completion of each dose level, a Data Safety Monitoring Committee has met to review all AEs to approve or deny escalation to the next highest dose level

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