Abstract CT234: A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors
Authors: Dumbrava Ecaterina Elena , Olson Daniel , Saibil Samuel , Pieke Brooke , George Mridula A. , Bouvier Riemke , Gavriliuc Miriam , Gruber Kelly , Moss Kara , Ternus Nathan , Apostolopoulou Maria , Adib Deyaa , Schlechter Benjamin L. 
Published: April 2023

Abstract
Background: Despite recent therapeutic developments for patients with advanced, metastatic, unresectable HER2+ solid tumors, significant unmet medical needs still exist, especially in tumors other than breast and gastric. The T cell antigen coupler (TAC) technology is a novel approach to modifying T cells, allowing them to recognize and treat HER2+ solid tumors. The TAC receptor redirects T cells to tumor cells, and upon tumor cell recognition, co-opts the natural T cell receptor (TCR) to yield safer anti-tumor responses versus chimeric antigen receptor (CAR) T cells. In preclinical studies, TAC T cells led to complete tumor clearance in mouse models of human cancer, without any TAC-related toxicities. In the ongoing clinical trial (NCT04727151), TAC01-HER2 treatment of HER2+ solid tumors is hypothesized to result in safe and effective anti-tumor responses. Subjects undergo leukapheresis, bridging therapy (if needed) while their TAC01-HER2 are engineered, lymphodepletion chemotherapy (LDC), and finally TAC01-HER2 infusion.
Trial Design and Early Results: In phase I dose escalation, the primary objective is to evaluate the safety of TAC01-HER2 at increasing doses of 0.3, 0.8, 3, and 8 × 106 cells/kg in HER2+ solid tumors (1+, 2+ or 3+ as identified by immunohistochemistry) in adult subjects who have progressed after ≥2 lines of systemic therapy. Dose limiting toxicities (DLTs) are assessed up to 28 days from cell infusion. In Phase II, dose expansion groups will further evaluate the safety, efficacy, and pharmacokinetics of the optimal TAC01-HER2 dose in HER2+ breast and other solid tumor types. As of 12 Dec 2022, 12 patients have been treated in Cohorts 1-4 with breast, colorectal, gall bladder, gastro-esophageal junction, gastric and ovarian tumors. No DLTs or neurotoxicity events have been reported. All patients treated so far at Cohorts 3 and 4 (3 × 106 and 8 × 106 cells/kg, respectively) experienced Grade ≤2 CRS which were resolved with standard of care treatments. Eight subjects have reported a total of 15 serious adverse events, all unrelated to TAC01-HER2 except for a Grade 1 and a Grade 2 CRS, both resolved with standard of care. Most adverse events were related to LDC or the underlying neoplasm. At Cohort 2, a partial response was observed in a subject with refractory metastatic gastric adenocarcinoma (3+ HER2) at 1st scan, with a 36.5% reduction in measurable disease and clinical benefit was maintained for 6 months. A 71% disease control rate was observed at Cohorts 2 and 3 at 1st scan (0.8 × 106 and 3 × 106 cells/kg, respectively)). Dose escalation of TAC01-HER2 is ongoing, with the first subject treated at Cohort 4. These results in a heavily pre-treated cancer population show manageable safety and promising clinical activity with a novel T cell therapy that may have broad clinical applicability in HER+ cancers.
Citation Format: Ecaterina Elena Dumbrava, Daniel Olson, Samuel Saibil, Brooke Pieke, Mridula A. George, Riemke Bouvier, Miriam Gavriliuc, Kelly Gruber, Kara Moss, Nathan Ternus, Maria Apostolopoulou, Deyaa Adib, Benjamin L. Schlechter. A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT234.