Vaccine, drug combo promising against HPV-related cancers
Combining a tumor-specific vaccine with an immune checkpoint inhibitor
shrank tumors in one third of patients with incurable cancer related to
HPV, according to a phase II clinical trial.
Participants were injected with the vaccine ISA101, which targets
important peptides from a cancer-promoting HPV16 genotype of human
papillomavirus, and nivolumab, a drug that blocks activation of PD-1 on T
cells. The findings were published Thursday in the Journal of the
Medical Association Oncology.
"That encouraging response rate is about twice the rate produced by PD1
checkpoint inhibitors in previous clinical trials, so these results will
lead to larger, randomized clinical trials of this combination,"
principal investigator Dr. Bonnie Glisson, a professor of thoracic/head
and neck medical oncology at MD Anderson in Houston, said in a press
release.
The vaccines, which are specific to HPV antigens on tumors, are known to
cause a strong immune response, but weren't active against established
cancers, Glisson said.
"Vaccines are revving up the immune system, but the immunosuppressive
tumor microenvironment probably prevents them from working," Glisson
said. "Our thinking was that inhibition of PD-1 would address one
mechanism of immunosuppression, empowering the vaccine-activated T
lymphocytes to attack the cancer."
Three previous clinical trials of PD1 inhibitors alone for recurrent
HPV-related cancers yielded response rates ranging from 16 to 22 percent
in three trials.
HPV causes nearly every cervical cancer, as well as most oropharyngeal, anal, penile, vulvar and vaginal cancers.
The study included 24 patients with recurrent HPV16-related cancers,
including 22 with oropharyngeal, or back of the throat, one with
cervical cancer and one with anal cancer. They were enrolled between
2015 and 2016 and researchers followed-up with them for an average of
12.2 months through last August.
Seventy percent of patients survived 12 months, with the overall median
survival 17.5 months and progression-free survival was 2.7 months
Eight of them had a tumor response -- for oropharyngeal cancer -- with a median duration of 10.3 months.
"The median survival of 17.5 months for these patients is promising and
provides further support for randomized trials testing the contribution
of ISA101 to PD-1 inhibition," Glisson said.
Two patients had elevated enzyme levels that required them to
discontinue nivolumab, but the researchers said they saw no sign of
synergistic side effects caused by the combination.
"That's important as we develop rational combination immunotherapy," Glisson said.
Randomized clinical trials of the combination are being organized, the researchers said.
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