Safety of administration of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, before curative-intent treatment in patients with HPV16+ oropharyngeal squamous cell carcinoma.

e18086 Background: Relapse is the primary cause of treatment failure after curative-intent treatment (chemoradiotherapy or surgery and adjuvant therapy) for human papillomavirus (HPV)+ oropharyngeal squamous cell carcinoma (OPSCC). Most cases of HPV+ OPSCC are caused by the HPV16 genotype. HPV16 E7 is a promising immunologic target that has high epitope affinity for HLA-A*0201, the most common class I allele in the USA. CUE-101 is a novel fusion protein comprised of the HPV16 E7 11-20 epitope, HLA-A*0201, a reduced affinity human IL2 variant, and an effector attenuated human IgG1 Fc domain. In a phase 1 trial (NCT03978689) of HLA-A*0201+ patients with relapsed HPV16+ OPSCC, CUE-101 was well tolerated, resulted in expansion of target HPV16 E7 11-20 -specific CD8+ T cells, and showed durable disease control in some patients. In this Phase 2 trial (NCT04852328), CUE-101 was administered in three schedules (A, B, and C) before curative-intent treatment to HLA-A*0201+ patients with HPV16+ OPSCC. Primary objectives for each schedule were to evaluate the safety of CUE-101 and assess the change in frequency of activating HPV16 E7 11-20 -specific CD8+ T cells in blood and tumor. Methods: This non-randomized Phase 2 trial evaluated three schedules of CUE-101 administered to HLA-A*0201+ patients with HPV16+ OPSCC. Each schedule enrolled 10 patients. CUE-101 (4 mg/kg IV) was administered 14 days (Schedule A), 14 and 7 days (Schedule B), or 7 days (Schedule C) before curative-intent treatment. Adverse events (AE) were assessed (NCI-CTCAE v5.0) at baseline, during, and through 1 year after CUE-101 administration. If Schedule A was safe, Schedule B and then C commenced. A schedule was deemed safe if no grade 5 treatment or research-related (TR) AE occurred AND if <2 of 10 patients experienced grade 3-4 TRAEs and/or delays of curative-intent treatment by >7 days from planned start date. Safety data for Schedules A and B are presented here. Results: Ten patients enrolled in each schedule. No patient experienced a Grade 5 TRAE or delay of >7 days from planned start date of curative-intent treatment. No patient in schedule A and 1 patient in schedule B experienced a grade 3-4 TRAE (grade 3 oral hemorrhage due to research-related tumor biopsy). The most common CUE-101-related AEs (all grade 1-2) in schedules A and B included fever (A: 4 patients; B: 6 patients), chills (2; 5), rash (4; 3), myalgia (2; 5), fatigue (3; 1), infusion-related reaction (0; 3), nausea (0; 1), vomiting (1; 0), back pain (0; 1), eosinophilia (3; 6), alanine/aspartate aminotransferase elevation (2; 4), and anemia (0; 1). Conclusions: Administration of CUE-101 (4 mg/kg IV) 14 days (Schedule A) and 14 and 7 days (Schedule B) before curative-intent treatment was safe and tolerable. Follow-up in Schedules A and B is ongoing. Schedule C is actively accruing patients. Clinical trial information: NCT04852328 .