A Phase 2 clinical trial found that the combination of Opdivo (nivolumab) and a cancer vaccine increased response rates in patients with throat tumors (oropharyngeal tumors) caused by the human papillomavirus (HPV) type 16, when compared with Opdivo treatment alone.
The trial results were reported at the recent European Society for Medical Oncology (ESMO) 2017 Congress in a presentation titled, “Nivolumab and ISA 101 HPV vaccine in incurable HPV-16+ cancer,” and in a conference press release.
The U.S. Food and Drug Administration approved Bristol-Myers Squibb’s Opdivo for treating recurrent or metastatic head and neck cancers in 2016. The decision was based on results from the Phase 3 CheckMate-141 trial (NCT02105636).
In the latest Phase 2 trial (NCT02426892), which was discussed at the ESMO 2017 Congress, treatment with Opdivo was combined with an HPV-16 vaccine, ISA 101, in treating cancers that tested positive for this type of HPV.
ISA 101, developed by ISA Pharmaceuticals, is a cancer vaccine containing 13 synthetic parts of HPV-16 proteins. This strain is responsible for more than 85% of head and neck cancers, anal cancers, and premalignant lesions, and 50% of cervical cancers.
Opdivo is a type of therapy called a checkpoint inhibitor, which frees up the body’s own immune system to kill tumor cells.
The trial enrolled 24 patients with incurable HPV-16 positive tumors, 22 of them with cancers located in the oropharynx. Participants were vaccinated with ISA 101 at the beginning of the trial and received Opdivo intravenously every two weeks for up to one year.
Eight patients, or 33%, saw their tumors shrink after treatment, two of them achieving a complete response. Three patients had stable disease. This overall response rate compares favorably to the 16% of patients who responded to Opdivo alone in the Checkmate 141 study.
Patients who responded tended to have a protein on their tumor cells targeted by Opdivo.
Secondary objectives included tolerability, progression-free survival (PFS), and overall survival (OS). At six months, 74% of patients were alive, and 33% of respondents had not seen their disease progress.
Mild to moderate adverse reactions were seen in 14 patients. They included fever, reactions at the injection site, and fatigue and nausea in one patient. Two patients had more severe reactions.
“These data suggest that the efficacy of vaccine-induced T-cells can be augmented by anti-PD-1 therapy, mitigating the influence of an immunosuppressive microenvironment. Our findings merit confirmation in a larger randomized trial,” the researchers concluded.
Helen Gogas, professor of medical oncology at the National and Kapodistrian University of Athens, Greece, said that the “strengths of the study are strong rationale (HPV-positive tumour microenvironment is immunosuppressive); [a] strong translational research component … and promising results.”