A Phase 1 Dose-escalation and Expansion Study of CUE-101, Given As Monotherapy in 3rd Line and in Combination with Pembrolizumab in 1st Line Recurrent/Metastatic (R/M) HPV16+ Head and Neck Cancer Patients

Purpose/Objective(s) Immuno-STATs are T cell engagers which activate tumor-antigen specific CD8+ T cells via targeted delivery of cytokines. CUE-101 is a human leukocyte antigen (HLA) complex, HLA-A*0201, plus an HPV16 E7 peptide, and 4 molecules of attenuated IL-2 designed activate HPV16-specific CD8+ T cells. Materials/Methods CUE-101-01 is an ongoing first-in-human study in HLA-A*0201 patients with HPV16+ R/M HNSCC. Escalating doses of CUE-101 were evaluated in platinum or ICB refractory R/M HNSCC, or with pembrolizumab in 1st line R/M HNSCC, followed by expanded enrollment at the RP2D. Safety, PK/PD, and antitumor activity were assessed. Results As of Oct 1, 2023, 76 patients have been enrolled. Following monotherapy and combination therapy dose escalation, 4 mg/kg of CUE-101 was chosen as the RP2D for both cohorts. Enrollment in both monotherapy and combination cohorts is now complete. Grade 3 treatment-related AEs reported include infusion-related reaction (4.2%), fatigue, maculopapular rash, stomatitis and diarrhea (all 2.7%). Among 19 evaluable monotherapy RP2D patients, 1 PR and 6 durable SD (SD ≥ 12 weeks) were observed, with mOS of 20.8 months. Among 17 evaluable RP2D combination patients, 1 CR, 7 PRs, and 3 durable SDs were observed. Complete Response and 5 out of 7 PRs occurred in tumors with CPS of 20 or less. Of the 8 patients with objective responses, 5 achieved >99% reduction in HPV16 cfDNA, 4 by week 6, with 3 patients pending analysis at time of data cut-off. Conclusion CUE-101 demonstrates safety, tolerability and meaningful anti-cancer activity. Patients treated with CUE-101 monotherapy in 3L showed a long OS. CUE-101 and pembrolizumab combination resulted in an ORR of 47% and decrease in HPV16 cfDNA in the 1L treatment of patients with HPV16+ R/M HNSCC.