Erminia Massarelli, MD
Bonnie Glisson, MD
In a single-center phase II study reported in JAMA Oncology, Erminia Massarelli, MD, and colleagues found combining tumor-specific vaccine and nivolumab (Opdivo) showed evidence of activity in incurable human papillomavirus (HPV) 16–related cancer. The therapeutic vaccine, ISA 101, induces HPV-specific T cells. Bonnie Glisson, MD, of the Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for the JAMA Oncology article.
In the trial, 24 patients at The University of Texas MD Anderson Cancer Center enrolled between December 2015 and December 2016 received ISA 101 subcutaneously on days 1, 22, and 50, and nivolumab every 2 weeks beginning on day 8, for up to 1 year. Among the patients, 22 had oropharyngeal cancer and 20 were male; treatment was first-line for recurrent disease in 42% of patients and second-line in 58%.
Response and Toxicity
Objective response on RECIST v1.1 criteria occurred in eight patients (33%, complete response in two), all with oropharyngeal cancer. Median duration of response was 10.3 months, with response continuing at time of analysis in five patients. Responses were observed in platinum- and cetuximab (Erbitux)-refractory disease. Median progression-free survival was 2.7 months, and median overall survival was 17.5 months.
An additive adverse event profile was observed, including injection-site reaction and fever associated with ISA 101 and fatigue, diarrhea, and hepatotoxicity associated with nivolumab. Grade 3 or 4 adverse events occurred in two patients, consisting of asymptomatic grade 3 transaminase level elevation in one and grade 4 lipase and amylase elevation in one; nivolumab was discontinued in both patients. No other dose-limiting toxicities were observed.
The investigators concluded, “The overall response rate of 33% and median overall survival of 17.5 months is promising compared with [programmed cell death 1, 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 warranted for further study.” ■