Median progression-free survival was 2.7 months (95% CI, 2.5-9.4 a few months). of sufferers. Healing HPV vaccines possess produced strong immune system replies to HPV-16, but vaccination by itself has been inadequate for invasive malignancy. Objective To determine whether the efficacy of nivolumab, an antiCPD-1 immune checkpoint antibody, is usually amplified through treatment with ISA 101, a synthetic long-peptide HPV-16 vaccine inducing HPV-specific T cells, in patients with incurable HPV-16Cpositive malignancy. Design, Setting, and Participants In this single-arm, single-center phase 2 clinical trial, 24 patients with incurable HPV-16Cpositive malignancy were enrolled from December 23, 2015, to December 12, 2016. Duration of follow-up for censored patients was 12.2 months through August 31, 2017. Interventions The vaccine ISA101, 100 g/peptide, was given subcutaneously on days 1, 22, and 50. Nivolumab, 3 mg/kg, was given intravenously every 2 weeks beginning day 8 for up to 1 year. Main Outcomes and Steps Assessment of efficacy reflected in the overall response rate (per Response Evaluation Criteria in Solid Tumors, version 1.1). Results Of the 24 patients (4 women and 20 men; Hhex 22 with oropharyngeal malignancy; median age, 60 years [range, 36-73 years]), the overall response rate was 33% (8 patients; 90% CI, 19%-50%). Median duration of response was 10.3 months (95% CI, 10.3 months to inestimable). Five of 8 patients remain in response. Median progression-free survival was 2.7 months (95% CI, 2.5-9.4 months). Median overall survival was 17.5 months (95% CI, 17.5 months to inestimable). Grades 3 to 4 4 toxicity occurred in 2 patients (asymptomatic grade 3 transaminase level elevation in 1 patient and grade 4 lipase elevation in 1 patient), requiring discontinuation of nivolumab therapy. Conclusions and Relevance The overall response rate of 33% and median overall survival of 17.5 months is promising compared with PD-1 inhibition alone in similar patients. A randomized clinical trial to confirm the contribution of HPV-16 vaccination to tumoricidal effects of PD-1 inhibition is usually warranted for further study. Trial Registration ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT02426892″,”term_id”:”NCT02426892″NCT02426892 Key Points Question Is the efficacy of programmed cell death 1 immune checkpoint inhibition increased by a tumor-specific vaccine in patients with incurable human papillomavirus 16Cpositive malignancy? Findings In this phase 2 clinical trial of nivolumab and human papillomavirus 16 vaccine ISA101, the primary end point was met, with a 33% overall Pseudohypericin response rate (8 of 24 patients), compared with response rates of 16% to 22% with programmed cell death 1 inhibitors alone in similar patients. Survival data were also encouraging, with a median survival of 17.5 months. Meaning These data show that HPV-16 vaccination may augment the efficacy of programmed cell death 1 checkpoint inhibition and merit confirmation in a randomized trial. Introduction Human papillomavirus (HPV) is the cause of nearly all cervical cancers and most oropharyngeal, anal, penile, vulvar, and vaginal cancers. Although many cancers are cured with initial treatment, recurrent malignancy is frequently incurable Pseudohypericin and Pseudohypericin associated with relatively short survival. The E6 and E7 viral proteins, crucial in driving HPV oncogenesis and foreign to the human immune system, represent ideal targets for therapeutic malignancy vaccination. Recent data show that, at initial diagnosis, most patients with HPV-positive oropharyngeal malignancy (OPC) exhibit a strong spontaneous immune response to HPV antigens that is associated with substantial infiltration of the malignancy with HPV-specific T cells and an excellent prognosis1. However, in recurrent HPV-positive OPC, immune checkpoint blockade with antiCprogrammed cell death 1 (PD-1) antibodies pembrolizumab and nivolumab produces tumor regression in only a minority of patients.2,3,4,5 Thus, we hypothesized that augmentation of the HPV-specific T-cell population by a therapeutic vaccine could increase the proportion of patients benefiting from antiCPD-1 therapy. The vaccine ISA101, which is among the most promising vaccines targeted to E6 and E7, consists of 9 overlapping long E6 peptides (five 32-mer E6 peptides and Pseudohypericin four 25-mer E6 peptides) and 4 overlapping 35-mer E7 peptides (synthetic long peptide HPV-16 vaccine),.