1528P A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors

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 lymphodepletion chemotherapy (LDC) 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 safety, efficacy, and pharmacokinetics of the optimal TAC01-HER2 dose in gastric/GEJ tumors. As of 23 April 2023, 19 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 CRS which resolved with supportive therapy. Thirteen subjects have reported a total of 26 serious adverse events, with 1 G3 pneumonitis, 1 G1, 3 G2 and 1 G3 CRS related to TAC01-HER2. A 67% disease control rate (DCR) was observed in Cohorts 2-4 at 4 weeks restaging after TAC01-HER2 infusion. For gastric/GEJ subjects of the same Cohorts, DCR was 83%. Two patients had an unconfirmed partial response (uPR). At Cohort 4, a uPR 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 trastzumab and trastuzumab deruxtecan. Treatment with TAC01-HER2 showed manageable safety and promising clinical activity in a heavily pre-treated cancer population. Dose escalation is complete.