A phase 1 trial of HPV16 E7 T-cell receptor-engineered T cells in patients with relapsed/refractory HPV16-positive cancers (KITE-439 trial)

Patients with relapsed/refractory (r/r) HPV-associated epithelial cancers have a poor prognosis. Engineered T cells expressing a T cell receptor (TCR) specific for HPV16 E7 can induce tumor regression. We conducted a Phase 1 trial of KITE-439, an investigational autologous T-cell product expressing TCR specific for HPV16 E7 in patients with r/r HPV16+ epithelial cancers. CD4+ and CD8+ T cells selected from leukapheresed peripheral blood mononuclear cells were stimulated with anti-CD3/anti-CD28 antibodies followed by retroviral transduction and expansion in the presence of interleukin-7/15 and an AKT inhibitor. Patients received lymphodepleting chemotherapy (cyclophosphamide 30 mg/kg/day for 2 days and fludarabine 25 mg/m 2 /day for 5 days) followed by a single infusion of KITE-439 with daily IL-2 (2.5×10 5 IU/kg, up to 7 doses). The primary objectives were safety, tolerability, and efficacy; the primary endpoint was dose-limiting toxicities (DLTs). Eight HLA-A*02:01 + patients received KITE-439 (1×10 6 –1×10 8 cells/kg). No DLTs occurred during the trial. In all patients, KITE-439 cells were detected in peripheral blood within 7 days post-infusion. Three patients experienced Grade 1–2 cytokine release syndrome related to KITE-439 (resolved within 1–5 days) and 4 had KITE-439–related Grade 1–2 neurologic events (resolved within a day). One patient achieved a partial response (from Day 35 to Month 3) and 7 had a best response of stable disease. These results suggest that KITE-439 has an acceptable safety profile for the treatment of patients with HPV-associated epithelial cancers. Further studies are needed to determine optimal manufacturing conditions and T-cell characteristics required for enhanced antitumor activity.