Glimmers of hope for cancer vaccines as two neoantigen shots hit the mark

The early clinical responses are encouraging, although the patient numbers are small.

Efforts to develop effective, personalized cancer vaccines have been largely unsuccessful to date, but two phase 1 studies suggest the tide could be turning.

The results in the journal Nature add to the hope that the vaccines—which are directed at patients' specific cancer mutations—could be combined with immuno-oncology drugs such as checkpoint inhibitors and deliver a double whammy to tumors, removing a brake on the immune response while also directing it toward the cancer cells.

One of the studies, led by Catherine Wu, M.D., at the Dana-Farber Cancer Institute in Boston, put a personalized "neoantigen" vaccine developed by Fierce 15 company Neon Therapeutics through its paces.

Neoantigen vaccines are a new form of personalized immunotherapy in which antigens that are found in diseased tissues but not normally in healthy patients are used to develop targeted vaccines. Neon's peptide-based vaccine (NEO-PV-01) is made from up to 20 antigens harvested from patients' own tumor cells.

In the study, six patients with the skin cancer melanoma were given the vaccine at around the same time as they underwent surgery to remove the tumor in a bid to prevent recurrence. More than 70% of the peptides successfully generated measurable immune responses, and after over two years of follow-up, four of the six patients were recurrence-free.

That's a bit better than expected, as typically around half of patients with melanoma relapse in that timeframe. But there was also good news in the two patients who did see a recurrence, as treatment with PD-1 inhibitors such as Merck & Co's Keytruda (pembrolizumab) or Bristol-Myers Squibb's Opdivo (nivolumab) cleared the tumors and boosted the number of neoantigen-targeting white cells.

"This research shows that it is feasible to produce peptide-based personalized neoantigen vaccines, and these vaccines can generate immune responses with reliability and potency," Wu said. "The initial clinical data is intriguing and worthy of exploration beyond the adjuvant setting into patients with active disease with immuno-oncology combinations."

Neon told FierceBiotech earlier this year that it is expecting to have data from a trial of NEO-PV-01 plus Opdivo later this year, and will be starting additional combination trials with the vaccine before the end of 2017.

The second trial, led by Ugur Sahin of the University of Mainz in Germany, also enrolled patients with melanoma and deployed personalized, RNA-based vaccines developed by BioNTech that targeted up to 10 mutated proteins in each patient.

All 13 patients that participated in the study of the IVAC Mutanome vaccines developed an immune response against three or more cancer antigens that were unique to their individual tumors, and eight who had no visible tumors at the time of vaccination remained cancer-free 23 months later. The remaining five had relapses, but one treatment with a PD-1 blocker resulted in a complete response.

It's a massive boost for Mainz-based BioNTech and an early positive readout for the company and its partners, including Sanofi and Roche subsidiary Genentech, which have agreed to stump up hundreds of millions of dollars to push the technology.

"Each patient developed immune responses against multiple vaccine targets," said Sahin, who is founder and CEO of BioNTech. "This suggests that in principle, it may be possible to train a patient's immune system to help fight their cancer across a wide array of tumor types."

Commenting on the findings, Cornelis Melief—a cancer immunology specialist based at Leiden University in the Netherlands who was not involved in the trials—said they "confirm the potential" of the neoantigen approach, with fewer episodes of tumor recurrence or spread than would have been expected in these patient groups.

"Controlled, randomized phase 2 clinical trials with more participants are now needed to establish the efficacy of these vaccines in patients with any type of cancer that has enough mutations to provide sufficient neoantigen targets for this type of approach," he wrote in a Nature editorial.