An investigational cancer vaccine, MedImmune’s MEDI0457, can safely be used in combination with anti-PD-1 therapy to improve outcomes in patients with HPV-associated head and neck cancer, a study reports, detailing findings of a proof-of-concept trial in patients.
The study, “Immunotherapy targeting HPV 16/18 generates potent immune responses in HPV-Associated Head and Neck Cancer,” was published in the journal Clinical Cancer Research.
Human papillomavirus (HPV) — the most common sexually transmitted disease in the United States — is known to play a major role in the development of head and neck cancers.
MEDI0457, a DNA-based cancer vaccine, is being developed to treat HPV-associated cancers. It is designed to target the E6 and E7 oncogenes (genes that have the potential to cause cancer), which are expressed by tumor cells that have been infected by HPV types 16 and 18.
The vaccine has two components — VGX-3100 (which contains the DNA sequence for E6 and E7) and INO-9012 (a DNA sequence for immune activator IL-12).
MEDI0457 is injected into the patient’s muscle, and enters the cells after electroporation (application of a small electric pulse).
Once there, E6 and E7 start to become expressed, which triggers the immune system to recognize E6 and E7 proteins as foreign. This leads to the production of “killer” T-cells that identify and destroy cells expressing E6 and E7, including HPV-infected tumor cells.
Physicians often treat tumors with an immunotherapy known as programmed death (PD-1) receptor-directed antibodies. But a clinical response to PD-1 inhibitors are only realized in about 20% of patients with advanced head and neck squamous cell cancer.
For this reason, an open-label Phase 1b/2 trial (NCT02163057) tested if MEDI0457 could be safely given with PD-1 inhibitors to people with locally advanced head and neck squamous cell cancer, and — as a secondary goal — work to make the immune system more responsive to PD-1 immunotherapy.
Twenty-one patients were divided into two groups, each given four doses of MEDI0457. One group was treated with one dose prior to surgery and three afterward; the other was given all doses after chemotherapy and radiation treatment.
Of these patients, 18 showed higher E6/E7-specific T-cell activity in blood and tissues after a final dose, with activity lasting for three months. Biopsies on five tumors, taken before and after one vaccine dose, also showed evidence of T-cell infiltration and proteins associated with a cell-killing potential.
Safety was also reasonable, with MEDI0457 being well-tolerated and its use associated with mild injection site reactions but no grade 3-5 adverse events.
“We have not seen that kind of T cell infiltration with just one dose of a vaccine before,” Charu Aggarwal, MD, the study’s principal investigator, said in a press release. “These findings open the door for utilizing targeted immunotherapy approaches against specific cancer-causing targets like HPV.”
One patient in the trial progressed and developed metastatic disease. Of note, the patient was then treated with anti-PD-1 therapy and achieved a rapid and durable complete response — sustained, to date, for more than two years.
“The observation of a sustained complete clinical response after just 4 doses of nivolumab (ongoing for > 18 months) in a patient with progressive metastatic disease is remarkable,” the study said.
The researchers concluded that MEDI0457 may be used “as a complementary strategy to PD-1/PD-L1 inhibition in HPV-associated HNSCCa [advanced head and neck squamous cell cancer] to improve therapeutic outcomes.”