Treatment with a novel, synthetic, long-peptide HPV-16 vaccine plus nivolumab yielded promising response rates and survival outcomes among a small cohort of patients with incurable HPV-16-positive cancer, according to results from a single-arm phase 2 study.
The combination of the vaccine and anti-PD-1 immune checkpoint antibody induced an overall response rate of 33% and median OS of 17.5 months.
“That encouraging response rate is about twice the rate produced by PD-1 checkpoint inhibitors in previous clinical trials, so these results will lead to larger, randomized clinical trials of this combination,” Bonnie Glisson, MD, professor in the department of thoracic and head and neck medical oncology and Abell-Hanger Foundation distinguished professor at The University of Texas MD Anderson Cancer Center, said in a press release. “Vaccines are revving up the immune system, but the immunosuppressive tumor microenvironment probably prevents them from working. Our thinking was that inhibition of PD-1 would address one mechanism of immunosuppression, empowering the vaccine-activated T lymphocytes to attack the cancer.”
The analysis included 24 patients (median age, 60 years; men, n = 20) with incurable HPV-16-related cancers (oropharyngeal, n = 22; cervical, n = 1; anal, n = 1).
Patients received 100 mcg/peptide ISA101 (Isa Pharmaceuticals) on days 1, 22 and 50, and 3 mg/kg nivolumab (Opdivo, Bristol-Myers Squibb) every 2 weeks, beginning on day 8 for up to 1 year.
ORR per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 served as the primary endpoint.
Of the eight patients (ORR, 33%; 90% CI, 19-50) who initially responded to the combination for a median duration of 10.3 months, five remained in response at study cutoff.
Median PFS was 2.7 months (95% CI, 2.5-9.4) and median OS was 17.5 months (95% CI, 17.5 months to inestimable).
At 6 months, PFS was 37% (95% CI, 22-63) and OS was 75% (95% CI, 59-94). At 1 year, PFS was 25% (95% CI, 12-50) and OS was 70% (95% CI, 54-91).
Researchers observed a grade 3 transaminase level elevation in one patient, and grade 4 lipase elevation in another, which led to discontinuation of nivolumab.
“The results of our trial are among the first clinical data to support the general concept of combining cancer vaccination with immune checkpoint blockade to enhance efficacy of vaccine-activated T cells in the immunosuppressive tumor environment,” the researchers wrote. “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.” – by Jennifer Southall
Disclosures: The study was supported by Abell-Hangar Foundation Chair, University of Texas MD Anderson Cancer Center HPV-Related Cancers MoonShot, University of Texas MD Anderson Cancer Center Oropharynx Program Stiefel Gift, and University of Texas MD Anderson Cancer Center Support Grant P30CA016672. Bristol-Myers Squibb and ISA Pharmaceuticals approved the design of the study and reviewed the data presented. Glisson reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.