Abstract B035: A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors
Authors: Schlechter Benjamin , Dumbrava Ecaterina , George Mridula , Saibil Samuel , Butler Marcus , Antonio Giordano , Pieke Brooke , Gavriliuc Miriam , Lichtenstein Emily , Geisberger Jill , Apostolopoulou Maria , Moss Kara , Kirkwood D'Arcy , Dang Salina , Adib Deyaa , Olson Daniel 
Published: December 2023

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. 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. As of 28 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. Fourteen subjects have reported a total of 29 serious adverse events, with 1 G3 pneumonitis, 5 CRS (1 G1, 3 G2 and 1 G3) and 1 G3 bronchial hyperreactivity related to TAC01-HER2. A 68.8% 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 85.7%. 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 trastuzumab and trastuzumab deruxtecan. 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).

Citation Format: Benjamin Schlechter, Ecaterina Dumbrava, Mridula George, Samuel Saibil, Marcus Butler, Giordano Antonio, Brooke Pieke, Miriam Gavriliuc, Emily Lichtenstein, Jill Geisberger, Maria Apostolopoulou, Kara Moss, D'Arcy Kirkwood, Salina Dang, Deyaa Adib, Daniel Olson. A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B035.