medwireNews: The efficacy of programmed cell death protein 1 (PD-1) inhibition with nivolumab may be amplified by vaccination against human papillomavirus (HPV)-16 in patients with incurable HPV-16–positive cancer, phase II study data suggest.
The single-arm, single-center clinical trial involved 24 patients (83% men, median age 60 years) with recurrent HPV-16–positive cancer, including 22 with oropharyngeal cancer, one with anal cancer, and one with cervical cancer.
The patients were vaccinated with ISA101, a synthetic long-peptide HPV-16 vaccine inducing HPV-specific T cells, on days 1, 22, and 50, alongside treatment with nivolumab 3 mg/kg every 2 weeks for up to 1 year.
As reported in JAMA Oncology, two patients achieved a complete response and six achieved a partial response according to RECIST criteria, giving an overall response rate of 33%. A further three patients had stable disease, with the disease control rate at 46%.
The median response duration was 10.3 months, median progression-free survival (PFS) was 2.7 months, and median overall survival (OS) was 17.5 months.
At 6 months, PFS was 37% and OS was 75%, with corresponding rates of 25% and 70% observed at 12 months.
Bonnie Glisson (The University of Texas MD Anderson Cancer Center, Houston, USA) and co-investigators describe these survival rates as “encouraging for this population.”
They add that the median OS time and 12-month OS rate observed in the current study “are approximately double that observed for the CheckMate 141, Keynote-012, and Keynote-055 trials,” which investigated the efficacy of nivolumab (CheckMate) or pembrolizumab (KEYNOTE) in patients with p16-positive oropharyngeal cancer.
Furthermore, the addition of ISA101 to nivolumab “was very well tolerated.” Only two patients experienced severe toxicity that required discontinuation of nivolumab therapy, one due to asymptomatic grade 3 transaminase level elevation and the other due to grade 4 lipase elevation.
Glisson and team note that their findings “do not allow firm conclusions” as to whether vaccine-induced T-cell populations are responsible for the improved response compared with previous trials of nivolumab alone, because “only a subset of patients could be evaluated for HPV-16–specific immune responses with [interferon]-γ release.”
Therefore “[a] randomized clinical trial testing the contribution of ISA101 to PD-1 inhibition, in patients with platin-resistant HPV-16–positive recurrent [oropharyngeal cancer] is planned,” Glisson et al conclude.
By Laura Cowen
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