NCT04727151

TAC T-cells for the Treatment of HER2-positive Solid Tumors

A Phase 1/2 Trial Investigating the Safety and Efficacy of Autologous TAC T Cell Monotherapy, and TAC T Cells in Combination With Pembrolizumab, in Relapsed HER2-Positive Solid Tumors

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Triumvira Immunologics, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

TAC01-HER2 is a novel cell therapy that consists of genetically engineered autologous T cells expressing T-cell Antigen Coupler (TAC) that recognizes human epidermal growth factor receptor 2 (HER2). TAC directs T-cells to the targeted antigen (HER2), and once engaged with the target, activates them via the endogenous T cell receptor. This is an open-label, multicenter Phase 1/2 study that aims to establish safety, maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), pharmacokinetic profile and efficacy of TAC01-HER2 as a monotherapy, and in combination with pembrolizumab, in subjects with HER2 positive gastric and gastroesophageal adenocarcinoma.

Detailed description

The TAC technology is a novel approach to modifying T cells, herein referred to as TAC T cells, and using them in the treatment of solid tumors. TAC T cells are produced through genetic engineering, incorporating TAC receptors into a patient's own T cells. This redirects these enhanced T cells to specific cancer antigens, and upon recognition, activates them through the natural signaling pathways of the endogenous TCR. In the TAC01-HER2 engineered T cell product; TAC T cells recognize the HER2 protein present on the surface of tumor cells, and eradicate them. Consequently, it is hypothesized TAC01-HER2 will be potentially safe and effective in treating patients with HER2+ solid tumors and provide a clinically meaningful therapeutic benefit in patient populations with high unmet medical need. This is a first-in-human study investigating TAC01-HER2 to evaluate the safety, MTD or RP2D, PK, and efficacy in subjects with HER2+ solid tumors who have been treated after at least 2 lines of prior therapy in Phase 1 and after at least 2 lines and no more than 4 lines of prior therapy in Phase 2. In Phase 1, escalating doses of TAC01-HER2 will be evaluated to identify the RP2D using the classic keyboard design method. The monotherapy arm will treat all subjects with HER2-positive solid tumors that meet the eligibility criteria (completed). The combination arm will treat all 2+ or 3+ HER2-positive subjects with gastric or gastroesophageal AC who meet the eligibility criteria. In Phase 2, dose expansion groups will further evaluate the efficacy, safety, and PK of the MTD or RP2D for TAC01-CLDN18.2 in subjects with gastric and esophageal adenocarcinoma. In Phase 2, a Simon 3-stage design will be used to enroll up to 36 subjects in Group A (monotherapy arm) and 34 subjects in Group B (combination arm). In summary: * Phase I monotherapy arm: Dose escalation in any HER2-positive solid tumor (completed). * Phase I combination therapy arm: Dose escalation in combination with pembrolizumab in 2+ or 3+ HER2-positive gastric and gastroesophageal adenocarcinoma * Phase II: Dose expansion cohorts: 2+ or 3+ HER2-positive gastric or gastroesophageal adenocarcinoma treated with TAC01-HER2 as a monotherapy (Group A) or in combination with pembrolizumab (Group B).

Conditions

• HER2 Positive Gastric Cancer
• Metastatic HER2 Positive Gastroesophageal Junction Cancer

Interventions

Type	Name	Description
BIOLOGICAL	TAC01-HER2	TAC01-HER2 and: * fludarabine and cyclophosphamide, or * clofarabine and cyclophosphamide, or * bendamustine, or * cyclophosphamide
BIOLOGICAL	TAC01-HER2 plus pembrolizumab	TAC01-HER2 plus pembrolizumab and: * fludarabine and cyclophosphamide, or * clofarabine and cyclophosphamide, or * bendamustine, or * cyclophosphamide

Timeline

• Start date: 2021-04-19
• Primary completion: 2023-12-17
• Completion: 2024-03-25
• First posted: 2021-01-27
• Last updated: 2025-06-08
• Results posted: 2025-06-08

Locations

11 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study