TAC01-HER2 Showcases Early Clinical Activity in HER2-Overexpressed Solid Tumors

Sep 25, 2022

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TAC01-HER2 demonstrated early signals of clinical activity with a tolerable safety profile in patients with HER2-overexpressed solid tumors.

Benjamin L. Schlechter, MD

Benjamin L. Schlechter, MD

TAC01-HER2 demonstrated early signals of clinical activity with a tolerable safety profile in patients with HER2-overexpressed solid tumors, according to data from an interim analysis of the ongoing phase 1/2 TACTIC-02 trial (NCT04727151) presented at the 2022 ESMO Congress.

Data showed that a 42-year-old male with immunohistochemistry (IHC) 3+ HER2-positive, stage IVb metastatic gastric adenocarcinoma who was treated with dose level 2 of 6.8 x 105 cells/kg of TAC01-HER2 achieved a partial response. This patient had been previously treated with 2 lines of HER2-directed therapy plus chemotherapy and palliative radiation. At day 29, this patient experienced a -36.5% change in tumor volume.

Furthermore, this patient experienced an overall interval decreased size of previously noted metabolically active lymph nodes associated with the mass; however, persistent intense metabolic activity was noted in most of them.

Additionally, stable disease was observed in 2 patients: 1 patient had IHC 3+ gallbladder cancer, and the other had IHC 2+ colorectal cancer (CRC).

“The study is ongoing with further investigation of TAC01-HER2 in the remaining phase 1 trial, with enrollment in dose level 3 and patients consented for dose level 4,” lead study author Benjamin L. Schlechter, MD, of Dana-Farber Cancer Institute, and colleagues, wrote in a poster. “Phase 2 enrollment begins in 2023.”

The T-cell antigen coupler (TAC) enables the redirection of T cells to tumors cells with the goal of eliciting durable antitumor responses. In preclinical models, TAC-engineered T cells successfully eliminated tumor cells in vitro and in vivo without associated toxicities.

The open-label, multicenter TACTIC-02 trial is investigating TAC01-HER2 in patients with HER2-positive solid tumors—breast cancer, lung cancer, CRC, gastric cancer, endometrial cancer, ovarian cancer, and others—who have progressed on prior anticancer therapies.

To be eligible for enrollment, patients were required to have received at least 2 prior lines of therapy, at least 1 measurable lesion per RECIST v1.1 criteria, and an ECOG performance status of 0 or 1. Treatment-related toxicities from prior therapies must have resolved to grade 1 or baseline.

Following the collection of T cells and prior to the administration of TAC01-HER2, patients underwent lymphodepletion, which consisted of 3 consecutive days of fludarabine at 30 mg/m2 and cyclophosphamide at 300 mg/m2 with or without intravenous mesna. Thus far, 4 patients have been treated with TAC01-HER2 at thedose level 1 of 1.3 x 105 cells/kg, and 4 patients have received the dose level 2 of 6.8 x 105 cells/kg. Patients have been enrolled to receive dose level 3 of 1.3 x 106 cells/kg of TAC01-HER2, and the trial is enrolling patients to receive dose level 4 of 6.8 x 106 cells/kg.

The primary end points of the trial are dose-limiting toxicities and establishing the maximum tolerated dose. Secondary end points include overall response rate, duration of response, overall survival, establishing the recommended phase 2 dose, and safety.

The median age of patients enrolled to cohorts 1 or 2 was 65.5 years (range, 42-70), 62.5% were male, and 87.5% were White. Half of patients had an ECOG performance status of 0, and the other half had a status of 1. Moreover, 87.5% of patients had a HER2 expression of 3+, and 12.5% had a HER2 expression of 2+/ISH+. Regarding tumor type, 2 patients had gastric cancer, 2 patients had CRC, and 1 patient each had gastroesophageal junction cancer, gallbladder cancer, esophageal cancer, and rectosigmoid cancer.

The median number of prior lines of therapy was 4.5 (range, 2-12); the median number of prior lines of HER2-targeted therapy was 2 (range, 0-9). Prior HER2 therapies received included trastuzumab (Herceptin; n = 5), fam-trastuzumab deruxtecan-nxki (Enhertu; n = 3), and investigative agents (n = 5).

No dose-limiting toxicities were reported in cohorts 1 and 2. Additionally, no patients experienced cytokine release syndrome or immune effector cell–associated neurotoxicity of any grade.

The most common adverse effect (AE) of any grade was anemia, which occurred in all 8 patients. Additional any-grade AEs included decreased white blood cell count (n = 6), decreased neutrophil count (n = 6), increased alanine transaminase (n = 3), decreased platelet count (n = 2), and decreased lymphocyte count (n = 2).

Notably, all serious AEs reported have been attributed to causes unrelated to TAC01-HER2 infusions.


Schlechter BL, Dumbrava EEI, Olson D, et al. A phase I/II trial investigating safety and efficacy of autologous TAC T-cells targeting HER2 in relapsed or refractory solid tumors. Ann Oncol. 2022;33(suppl 7):S896. doi:10.1016/j.annonc.2022.07.904

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